{
 "manifest": {
  "name": "Human Repair Graph",
  "version": "0.3.0",
  "snapshot": "2026-09-11",
  "contentHash": "6c6db5f42d339ed08f70417b3e05726bb9e911aa69645fd82bcc7c4808a02187",
  "counts": {
   "capability": 185,
   "cell": 31,
   "claim": 24,
   "experiment": 6,
   "goal": 10,
   "question": 20,
   "route": 16,
   "source": 34
  },
  "reviewStates": {
   "ai-proposed": 289,
   "disputed": 3,
   "n/a": 34
  },
  "humanReviewed": 0,
  "projections": [
   {
    "id": "universal-repair",
    "name": "Universal Repair",
    "tagline": "From trauma and infection to cancer and organ failure."
   },
   {
    "id": "rejuvenation",
    "name": "Rejuvenation",
    "tagline": "From biological aging to restored youthful function."
   },
   {
    "id": "full-graph",
    "name": "Full Research Graph",
    "tagline": "Capabilities, dependencies, evidence, blockers, and next experiments.",
    "note": "Not a tag — the union. Every node is in the full graph."
   }
  ],
  "formats": {
   "json": "/graph/graph.json",
   "jsonl": "/graph/graph.jsonl",
   "jsonld": "/graph/graph.jsonld",
   "schemas": "/graph/schema/",
   "api": "/api/graph",
   "mcp": "/mcp"
  },
  "license": "CC BY 4.0 for graph data; sources remain under their publishers' terms",
  "caveat": "Every record carries its own review state. Unless it says reviewed with a named human, no human has opened its sources. This is a map of research state, not clinical advice."
 },
 "ontology": {
  "relationships": {
   "$comment": "Human Repair Graph — relationship vocabulary (v0.3). Deliberately small. Every relation says where it is STORED (one place only; the inverse is derived by the build, never hand-written, so the two can never disagree).",
   "version": "0.3.0",
   "relations": [
    {
     "name": "REQUIRES",
     "storedOn": "goal.requires | capability.requires",
     "shape": "array of groups: {\"all\": [ids]} means every member is needed (AND); {\"any\": [ids]} means one member suffices (OR). Groups are ANDed together.",
     "domain": [
      "goal",
      "capability"
     ],
     "range": [
      "goal",
      "capability"
     ],
     "inverse": "ENABLES (derived)",
     "semantics": "The dependent cannot be achieved without the requirement. An OR group records that nobody yet knows which alternative will succeed — that uncertainty is data, not a modelling shortcut.",
     "note": "ALTERNATIVE_TO is not a separate relation: two capabilities in the same {any} group are alternatives for that requirement."
    },
    {
     "name": "ENABLES",
     "storedOn": "(derived)",
     "domain": [
      "capability",
      "goal"
     ],
     "range": [
      "capability",
      "goal"
     ],
     "inverse": "REQUIRES",
     "semantics": "X enables Y iff Y requires X. Computed at build time; a hand-written enables list would be a second copy of the same fact."
    },
    {
     "name": "BLOCKED_BY",
     "storedOn": "capability.blockedBy | goal.blockedBy",
     "domain": [
      "capability",
      "goal"
     ],
     "range": [
      "question"
     ],
     "inverse": "BLOCKS (derived)",
     "semantics": "An open question whose answer gates progress on this capability. The capability's grade.blocked field says which KIND of thing blocks it (science vs framework); this relation says WHICH unresolved question."
    },
    {
     "name": "SUPPORTS",
     "storedOn": "claim.supports",
     "domain": [
      "claim",
      "route"
     ],
     "range": [
      "capability",
      "goal"
     ],
     "inverse": "SUPPORTED_BY (derived)",
     "semantics": "The claim, if true, is evidence that the capability has been demonstrated at (at least) the claim's rung. A capability's grade must be traceable to at least one supporting claim or an explicit 'no evidence located'."
    },
    {
     "name": "CONTRADICTS",
     "storedOn": "claim.contradicts",
     "domain": [
      "claim"
     ],
     "range": [
      "claim",
      "capability"
     ],
     "inverse": "CONTRADICTED_BY (derived)",
     "semantics": "Direct tension: the two cannot both be true as stated, or the claim is a null/negative result against the capability. Never resolved by deletion — both stay, and a question should exist that would discriminate."
    },
    {
     "name": "REPLICATES",
     "storedOn": "claim.replicates",
     "domain": [
      "claim"
     ],
     "range": [
      "claim"
     ],
     "inverse": "REPLICATED_BY (derived)",
     "semantics": "Same finding, different group. Only counts as independent when the groups share no senior author and no sponsor — the L5 rung rests on this word, and the map has already had to demote one record for misusing it (Brineura, 2026-07-27)."
    },
    {
     "name": "TESTS",
     "storedOn": "experiment.tests",
     "domain": [
      "experiment"
     ],
     "range": [
      "question"
     ],
     "inverse": "TESTED_BY (derived)",
     "semantics": "Running this experiment would produce an observation that discriminates between the question's live hypotheses."
    },
    {
     "name": "RESOLVES",
     "storedOn": "question.resolvedBy",
     "domain": [
      "question"
     ],
     "range": [
      "claim"
     ],
     "inverse": "RESOLVES (as seen from the claim)",
     "semantics": "A claim whose acceptance closed (or would close) the question. A question with a non-empty resolvedBy and state 'open' is a contradiction the build rejects."
    },
    {
     "name": "MEASURES",
     "storedOn": "claim.measurement",
     "domain": [
      "claim"
     ],
     "range": [
      "measurement object"
     ],
     "semantics": "What was actually observed, separate from what was concluded. The observation survives even if every interpretation of it is later overturned."
    },
    {
     "name": "CITES",
     "storedOn": "claim.evidence[].source",
     "domain": [
      "claim",
      "route"
     ],
     "range": [
      "source"
     ],
     "semantics": "Every evidence item points at exactly one source record with a locator (figure, table, page, section). A claim with no evidence cannot enter the map."
    },
    {
     "name": "TARGETS",
     "storedOn": "capability.target.node",
     "domain": [
      "capability"
     ],
     "range": [
      "cell"
     ],
     "semantics": "The grid node (cell type or non-cellular structure) this capability acts on. Derived grid capabilities (one per cell × class) always carry it; hand-authored capabilities carry it when they are specific to a node."
    },
    {
     "name": "PROJECTS_TO",
     "storedOn": "goal.projections | capability.projections",
     "domain": [
      "goal",
      "capability",
      "question"
     ],
     "range": [
      "projection id"
     ],
     "semantics": "Which public map(s) show this node: universal-repair, rejuvenation, or both. Projections are views over ONE graph; a node never exists twice."
    }
   ],
   "projections": [
    {
     "id": "universal-repair",
     "name": "Universal Repair",
     "tagline": "From trauma and infection to cancer and organ failure."
    },
    {
     "id": "rejuvenation",
     "name": "Rejuvenation",
     "tagline": "From biological aging to restored youthful function."
    },
    {
     "id": "full-graph",
     "name": "Full Research Graph",
     "tagline": "Capabilities, dependencies, evidence, blockers, and next experiments.",
     "note": "Not a tag — the union. Every node is in the full graph."
    }
   ]
  },
  "primitives": {
   "$comment": "Human Repair Graph — the two vocabularies every capability is classified by. Both come from the owner's founding draft (owner-draft-2026-07-26.md): the five pillars became the five grid columns in v0.2; the action primitives are her 'useful hierarchy'. Neither list is open-ended: adding a member is an explicit, logged decision.",
   "version": "0.3.0",
   "classes": [
    {
     "id": "see",
     "name": "Sense",
     "question": "Can we measure the state of this target in a living person?",
     "pillar": "CAP-01 sufficient biological sensing"
    },
    {
     "id": "model",
     "name": "Model",
     "question": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention?",
     "pillar": "CAP-02 target-state model"
    },
    {
     "id": "reach",
     "name": "Reach",
     "question": "Can we deliver something to it, specifically and repeatedly?",
     "pillar": "CAP-03 cell-specific access and delivery"
    },
    {
     "id": "edit",
     "name": "Edit",
     "question": "Can we repair, replace, reprogram, regenerate or clear it?",
     "pillar": "CAP-04 cell-state editing"
    },
    {
     "id": "verify",
     "name": "Verify",
     "question": "Can we confirm afterwards that it worked, and stayed working?",
     "pillar": "CAP-05 closed-loop verification"
    },
    {
     "id": "control",
     "name": "Control",
     "question": "Can we time, dose, localise and stop the intervention safely while it runs?",
     "pillar": "cross-cutting: safety, feedback, stopping rule",
     "note": "Added in v0.3 for the survival-phase capabilities (haemostasis, perfusion, stabilisation) that are neither an edit nor a measurement. The only class added since v0.2; logged here."
    }
   ],
   "primitives": [
    {
     "id": "stop",
     "name": "Stop what is destroying",
     "definition": "Halt a catastrophic process before it destroys something that cannot be recovered: bleeding, hypoxia, arrhythmia, shock, seizure, toxin, uncontained infection.",
     "phase": "seconds–minutes"
    },
    {
     "id": "remove",
     "name": "Remove what should not be there",
     "definition": "Pathogens, toxins, cancer cells, senescent cells, scar tissue, misfolded aggregates.",
     "phase": "minutes–days"
    },
    {
     "id": "repair",
     "name": "Repair what can be repaired",
     "definition": "DNA, mitochondria, proteins, membranes, epigenetic state — in place, in the existing cell.",
     "phase": "hours–weeks"
    },
    {
     "id": "replace",
     "name": "Replace what cannot be repaired",
     "definition": "Cells, tissues, organs, microbial communities.",
     "phase": "days–months"
    },
    {
     "id": "regenerate",
     "name": "Regenerate what is missing",
     "definition": "Limbs, nerves, cartilage, muscle, vasculature, appendages — new structure with correct architecture.",
     "phase": "weeks–months"
    },
    {
     "id": "reconnect",
     "name": "Reconnect what must communicate",
     "definition": "Neural circuits, immune regulation, endocrine loops, vascular continuity.",
     "phase": "weeks–months"
    },
    {
     "id": "recalibrate",
     "name": "Recalibrate control loops",
     "definition": "Immune, endocrine and metabolic signalling set-points.",
     "phase": "ongoing"
    },
    {
     "id": "preserve",
     "name": "Preserve what defines the person",
     "definition": "Memories, identity, learned abilities, preferences, agency, consent. Not an appendix: a system requirement every other primitive is constrained by.",
     "phase": "always"
    }
   ],
   "boundary": {
    "statement": "Repair is possible when the relevant information still exists, can be inferred, or has been backed up.",
    "source": "owner-draft-2026-07-26.md",
    "consequence": "Nodes whose target state cannot be inferred from surviving information (destroyed identity-bearing neural structure without a backup) are marked informationLimited: true and are never graded above L0 for 'restore the original', only for 'reconstruct a new one'."
   },
   "gradeLadder": {
    "$comment": "Unchanged from v0.1 (records/rubrics.json). Anchored on observables; independent replication is the anchor a lab cannot award itself.",
    "rungs": [
     "L0",
     "L1",
     "L2",
     "L3",
     "L4",
     "L5"
    ]
   },
   "blockedKinds": [
    {
     "id": "science",
     "definition": "We do not know how. The binding constraint is knowledge or capability."
    },
    {
     "id": "framework",
     "definition": "We know how, and it is not reaching people: approvals, ethics, economics, access, manufacturing."
    },
    {
     "id": "none",
     "definition": "Not blocked at the current rung; the next rung is a matter of running the demonstration."
    }
   ]
  },
  "reviewStates": {
   "$comment": "Human Repair Graph — review states and machine checks. The states are unchanged from v0.1 so that no existing record breaks. Machine checks are recorded separately from the state because a source existing is not the same as a human having read it — conflating the two is the failure this map exists to avoid.",
   "version": "0.3.0",
   "states": [
    {
     "id": "ai-proposed",
     "who": "an AI agent or an import script",
     "meaning": "Proposed with sources attached; no human has opened them. This is the default and it is shown on the record's face."
    },
    {
     "id": "submitted",
     "who": "a human contributor",
     "meaning": "A named human proposed or endorsed it, but has not been reviewed by a steward."
    },
    {
     "id": "in-review",
     "who": "a steward",
     "meaning": "A steward has taken it up. Verdicts accumulate in the event log."
    },
    {
     "id": "reviewed",
     "who": "a named human reviewer ONLY",
     "meaning": "A human opened every cited source and confirmed each supports the claim it is attached to. reviewedBy is required; the build refuses a 'reviewed' record without it."
    },
    {
     "id": "disputed",
     "who": "anyone, via a challenge",
     "meaning": "An open, public challenge exists. The record stays visible with the dispute attached; it is never silently edited."
    },
    {
     "id": "superseded",
     "who": "a steward",
     "meaning": "Replaced by a newer record. The old record and its history remain addressable forever."
    }
   ],
   "transitions": {
    "ai-proposed": [
     "submitted",
     "in-review",
     "disputed",
     "superseded"
    ],
    "submitted": [
     "in-review",
     "disputed",
     "superseded"
    ],
    "in-review": [
     "reviewed",
     "disputed",
     "submitted",
     "superseded"
    ],
    "reviewed": [
     "disputed",
     "superseded"
    ],
    "disputed": [
     "in-review",
     "reviewed",
     "superseded"
    ],
    "superseded": []
   },
   "humanGated": {
    "$comment": "From ai-collaboration.md §4 — the right-hand column that never moves.",
    "onlyHumansMay": [
     "set review.state to 'reviewed'",
     "set or change a capability grade on a reviewed record",
     "resolve a dispute",
     "author target-state / ethics content",
     "accept a safety claim"
    ]
   },
   "checks": [
    {
     "id": "source-resolved",
     "by": "machine",
     "meaning": "The cited source exists and its metadata (title, venue, year, DOI/PMID) matches the record. Says nothing about whether it supports the claim."
    },
    {
     "id": "cross-checked",
     "by": "machine",
     "meaning": "A second, different model independently re-extracted the claim from the same source and agreed. Single-model consensus counts as one vote."
    },
    {
     "id": "human-opened-source",
     "by": "human",
     "meaning": "A named person opened the source at the locator and read the passage. The only check that can precede 'reviewed'."
    },
    {
     "id": "independently-replicated",
     "by": "human",
     "meaning": "A steward confirmed the REPLICATES edge is between groups sharing no senior author or sponsor."
    }
   ]
  },
  "mappings": {
   "$comment": "Human Repair Graph — how our identifiers and terms line up with the standards that already exist. We do not redefine gene, protein, disease, phenotype, cell, anatomy, chemical or organism; we point at the vocabularies that do. Only the repair-specific concepts are ours.",
   "version": "0.3.0",
   "idScheme": {
    "pattern": "hrm:<type>/<slug>",
    "types": [
     "goal",
     "capability",
     "question",
     "claim",
     "experiment",
     "source",
     "cell",
     "route",
     "prediction"
    ],
    "slug": "^[a-z0-9]+(-[a-z0-9]+)*(--[a-z0-9]+(-[a-z0-9]+)*)?$",
    "rules": [
     "An id is never renamed. A wrong id is superseded by a new record and the old one keeps resolving.",
     "The double dash joins a target and a class in DERIVED grid capabilities only: hrm:capability/cardiomyocyte--reach.",
     "IRIs: prefix hrm: expands to https://humanrepairmap.com/graph/ so every id is also a resolvable URL."
    ]
   },
   "prefixes": {
    "hrm": "https://humanrepairmap.com/graph/",
    "NCBITaxon": "http://purl.obolibrary.org/obo/NCBITaxon_",
    "CL": "http://purl.obolibrary.org/obo/CL_",
    "UBERON": "http://purl.obolibrary.org/obo/UBERON_",
    "MONDO": "http://purl.obolibrary.org/obo/MONDO_",
    "HP": "http://purl.obolibrary.org/obo/HP_",
    "GO": "http://purl.obolibrary.org/obo/GO_",
    "CHEBI": "http://purl.obolibrary.org/obo/CHEBI_",
    "DOID": "http://purl.obolibrary.org/obo/DOID_",
    "EFO": "http://www.ebi.ac.uk/efo/EFO_",
    "NCIT": "http://purl.obolibrary.org/obo/NCIT_",
    "doi": "https://doi.org/",
    "pmid": "https://pubmed.ncbi.nlm.nih.gov/",
    "pmcid": "https://www.ncbi.nlm.nih.gov/pmc/articles/",
    "nct": "https://clinicaltrials.gov/study/",
    "orcid": "https://orcid.org/",
    "ror": "https://ror.org/",
    "biolink": "https://w3id.org/biolink/vocab/",
    "prov": "http://www.w3.org/ns/prov#",
    "schema": "https://schema.org/"
   },
   "externalVocabularies": {
    "species": "NCBITaxon (human 9606, mouse 10090, rat 10116, pig 9823, rhesus 9544, Acomys cahirinus 10068)",
    "cellType": "CL (Cell Ontology)",
    "tissue": "UBERON",
    "disease": "MONDO (DOID acceptable)",
    "phenotype": "HP",
    "process": "GO biological process",
    "chemical": "CHEBI",
    "trial": "ClinicalTrials.gov NCT id",
    "person": "ORCID",
    "institution": "ROR",
    "publication": "DOI, then PMID; PMCID when open"
   },
   "ourConcepts": {
    "$comment": "The genuinely new terms. Each says what it is closest to in Biolink/PROV so a graph tool can at least approximate it.",
    "Goal": {
     "closest": "biolink:NamedThing",
     "note": "A repair outcome stated from the person's side (scarless functional skin repair). Not a disease."
    },
    "Capability": {
     "closest": "biolink:NamedThing",
     "note": "Something humanity must be able to DO to a target, graded L0–L5 on demonstrated evidence, with what blocks it."
    },
    "Question": {
     "closest": "schema:Question",
     "note": "An unresolved uncertainty whose answer changes a grade or a dependency. The unit of research prioritisation."
    },
    "Claim": {
     "closest": "biolink:Association",
     "note": "subject–predicate–object with explicit context, measurement, evidence and provenance. The unit of knowledge is not the paper."
    },
    "Experiment": {
     "closest": "schema:Action",
     "note": "A candidate or completed study that TESTS a question. Cost and duration are classes, never invented numbers."
    },
    "Source": {
     "closest": "biolink:Publication / schema:CreativeWork",
     "note": "Where a claim's evidence lives, with a machine resolution record separate from human reading."
    },
    "Prediction": {
     "closest": "prov:Entity",
     "note": "A locked forecast about a question or claim by a named human or a named model version, resolved later against reality."
    },
    "requires (all/any)": {
     "closest": "none",
     "note": "AND/OR requirement groups. No standard biomedical vocabulary carries research dependency; this is the map's own contribution."
    }
   },
   "provenanceAlignment": {
    "provenance.proposedBy": "prov:wasAttributedTo",
    "provenance.method": "prov:wasGeneratedBy (an Activity)",
    "provenance.evidenceAccessed": "prov:used",
    "review.history[]": "prov:wasRevisionOf chain, one entry per state change"
   }
  }
 },
 "rubrics": {
  "ladder": [
   {
    "id": "L0",
    "label": "proposed",
    "blurb": "an idea or mechanism on paper; nothing built"
   },
   {
    "id": "L1",
    "label": "in a dish",
    "blurb": "works in cultured cells or an organoid"
   },
   {
    "id": "L2",
    "label": "in a rodent",
    "blurb": "works in a living mouse or rat"
   },
   {
    "id": "L3",
    "label": "in a large animal",
    "blurb": "works in a non-human primate or comparable model"
   },
   {
    "id": "L4",
    "label": "in humans, once",
    "blurb": "shown in people by a single group, usually the originator"
   },
   {
    "id": "L5",
    "label": "in humans, independently",
    "blurb": "reproduced in people by a group with no stake in the claim"
   }
  ],
  "grounding": [
   {
    "id": "G0",
    "label": "assertion",
    "blurb": "someone said it; no source attached",
    "review": "cannot enter the map"
   },
   {
    "id": "G1",
    "label": "cited text",
    "blurb": "a paper or report says it",
    "review": "full verification packet + human"
   },
   {
    "id": "G2",
    "label": "structured record",
    "blurb": "registry entry, regulatory filing, trial record",
    "review": "automated cross-check; human spot-audit"
   },
   {
    "id": "G3",
    "label": "primary data",
    "blurb": "deposited dataset that can be re-analysed",
    "review": "automated re-analysis; human reviews method"
   },
   {
    "id": "G4",
    "label": "instrument-signed",
    "blurb": "signed at capture, provenance chain intact",
    "review": "none for the fact; human only for the inference"
   }
  ],
  "measured": {
   "function": "changed a person's life (motor milestones, survival, tumour response)",
   "biomarker": "moved a surrogate number without proven clinical benefit",
   "opening": "demonstrated the barrier opens, not that a delivered drug helped",
   "none": "no clinical or surrogate benefit demonstrated"
  }
 },
 "schemas": {
  "capability.schema.json": {
   "$schema": "https://json-schema.org/draft/2020-12/schema",
   "$id": "https://humanrepairmap.com/schema/capability.schema.json",
   "title": "Capability",
   "description": "Something humanity must be able to DO to a target for repair to happen, graded on how far it has actually been demonstrated and what blocks the next rung. One file per capability under records/capabilities-graph/. The 155 grid capabilities (cell type × class) are DERIVED by the build from records/cells and are not stored as files.",
   "type": "object",
   "required": [
    "id",
    "type",
    "name",
    "class",
    "description",
    "projections",
    "grade",
    "provenance",
    "review"
   ],
   "additionalProperties": false,
   "properties": {
    "id": {
     "$ref": "common.schema.json#/$defs/id"
    },
    "type": {
     "const": "capability"
    },
    "name": {
     "type": "string",
     "minLength": 3,
     "maxLength": 160
    },
    "class": {
     "$ref": "common.schema.json#/$defs/capabilityClass"
    },
    "primitive": {
     "$ref": "common.schema.json#/$defs/primitive"
    },
    "description": {
     "type": "string",
     "minLength": 20,
     "description": "What 'having this capability' concretely means — phrased so that a demonstration either meets it or does not."
    },
    "target": {
     "type": "object",
     "properties": {
      "node": {
       "$ref": "common.schema.json#/$defs/id",
       "description": "The grid node (hrm:cell/...) this acts on, if specific."
      },
      "tissue": {
       "type": "string",
       "description": "UBERON id or label"
      },
      "cellType": {
       "type": "string",
       "description": "CL id or label"
      },
      "species": {
       "type": "string",
       "description": "NCBITaxon id of the target organism the grade refers to. Default human (9606)."
      }
     }
    },
    "projections": {
     "type": "array",
     "items": {
      "$ref": "common.schema.json#/$defs/projection"
     },
     "minItems": 1,
     "uniqueItems": true
    },
    "grade": {
     "type": "object",
     "required": [
      "basis",
      "note"
     ],
     "additionalProperties": false,
     "properties": {
      "basis": {
       "type": "string",
       "enum": [
        "claims",
        "standard-of-care",
        "no-evidence-located",
        "ungraded"
       ],
       "description": "claims: the grade is traceable to at least one claim that supports or contradicts this capability (the build enforces it). standard-of-care: routine clinical practice; the note must say what practice. no-evidence-located: a search was made and nothing was found; rung is L0. ungraded: the node exists so the gap is visible, but nobody has graded it yet; rung is absent."
      },
      "rung": {
       "$ref": "common.schema.json#/$defs/rung"
      },
      "measured": {
       "$ref": "common.schema.json#/$defs/measured"
      },
      "blocked": {
       "$ref": "common.schema.json#/$defs/blocked"
      },
      "note": {
       "type": "string",
       "minLength": 20,
       "description": "Why it sits at this rung — a grade without a reason cannot be checked."
      },
      "drift": {
       "type": "string",
       "description": "The distance between what was demonstrated and what is commonly claimed."
      },
      "searchedOn": {
       "$ref": "common.schema.json#/$defs/date",
       "description": "For no-evidence-located: when the search was made."
      }
     },
     "allOf": [
      {
       "if": {
        "properties": {
         "basis": {
          "enum": [
           "claims",
           "standard-of-care"
          ]
         }
        }
       },
       "then": {
        "required": [
         "rung",
         "measured",
         "blocked"
        ]
       }
      },
      {
       "if": {
        "properties": {
         "basis": {
          "const": "no-evidence-located"
         }
        }
       },
       "then": {
        "required": [
         "rung",
         "searchedOn"
        ],
        "properties": {
         "rung": {
          "const": "L0"
         }
        }
       }
      },
      {
       "if": {
        "properties": {
         "basis": {
          "const": "ungraded"
         }
        }
       },
       "then": {
        "not": {
         "required": [
          "rung"
         ]
        }
       }
      }
     ]
    },
    "requires": {
     "type": "array",
     "items": {
      "$ref": "common.schema.json#/$defs/requirementGroup"
     }
    },
    "blockedBy": {
     "$ref": "common.schema.json#/$defs/idList",
     "description": "Question ids that gate the next rung."
    },
    "informationLimited": {
     "type": "boolean",
     "description": "True when the target state cannot be inferred from surviving information (see ontology/repair-primitives.json boundary)."
    },
    "wouldMove": {
     "type": "string",
     "description": "The specific missing demonstration that would raise the rung."
    },
    "aliases": {
     "type": "array",
     "items": {
      "type": "string"
     }
    },
    "provenance": {
     "$ref": "common.schema.json#/$defs/provenance"
    },
    "review": {
     "$ref": "common.schema.json#/$defs/review"
    },
    "derived": {
     "type": "boolean",
     "description": "True for the grid capabilities the build derives from records/cells (one per node x class). Never stored as a file."
    }
   }
  },
  "claim.schema.json": {
   "$schema": "https://json-schema.org/draft/2020-12/schema",
   "$id": "https://humanrepairmap.com/schema/claim.schema.json",
   "title": "Claim",
   "description": "The unit of knowledge: one statement, the context it was shown in, what was measured, the evidence it rests on, and where every piece came from. A paper is not a claim; a paper is where claims live. Observation (measurement) and interpretation (statement, supports) are separate fields so the observation survives a later change of interpretation.",
   "type": "object",
   "required": [
    "id",
    "type",
    "statement",
    "context",
    "measurement",
    "evidence",
    "rung",
    "grounding",
    "provenance",
    "review"
   ],
   "additionalProperties": false,
   "properties": {
    "id": {
     "$ref": "common.schema.json#/$defs/id"
    },
    "type": {
     "const": "claim"
    },
    "statement": {
     "type": "string",
     "minLength": 20,
     "maxLength": 400,
     "description": "One sentence. Grade claims, never groups or companies. Absence is 'no independent evidence located as of <date>', never 'false'."
    },
    "triple": {
     "type": "object",
     "description": "Optional structured form: subject–predicate–object with external ids where they exist.",
     "properties": {
      "subject": {
       "type": "string"
      },
      "predicate": {
       "type": "string"
      },
      "object": {
       "type": "string"
      }
     }
    },
    "context": {
     "type": "object",
     "required": [
      "species"
     ],
     "properties": {
      "species": {
       "type": "string",
       "description": "NCBITaxon id or 'human'/'mouse'/... ; 'multiple' when the claim spans species and the evidence items say which."
      },
      "strain": {
       "type": "string"
      },
      "sex": {
       "type": "string"
      },
      "age": {
       "type": "string"
      },
      "model": {
       "type": "string",
       "description": "Injury or disease model: full-thickness excisional wound, diabetic foot ulcer, ..."
      },
      "tissue": {
       "type": "string"
      },
      "cellType": {
       "type": "string"
      },
      "intervention": {
       "type": "string"
      },
      "dose": {
       "type": "string"
      },
      "route": {
       "type": "string"
      },
      "timing": {
       "type": "string"
      },
      "comparator": {
       "type": "string"
      }
     }
    },
    "measurement": {
     "type": "object",
     "required": [
      "measured",
      "endpoint"
     ],
     "properties": {
      "measured": {
       "$ref": "common.schema.json#/$defs/measured"
      },
      "assay": {
       "type": "string"
      },
      "endpoint": {
       "type": "string"
      },
      "effect": {
       "type": "string",
       "description": "Direction and magnitude as reported, with units. Never a number the source does not state."
      },
      "uncertainty": {
       "type": "string"
      },
      "followUp": {
       "type": "string"
      }
     }
    },
    "evidence": {
     "type": "array",
     "minItems": 1,
     "items": {
      "type": "object",
      "required": [
       "source",
       "design"
      ],
      "additionalProperties": false,
      "properties": {
       "source": {
        "$ref": "common.schema.json#/$defs/id"
       },
       "locator": {
        "type": "string",
        "description": "Figure, table, page or section. Required before a record can be reviewed."
       },
       "quote": {
        "type": "string",
        "description": "Exact passage, when available. A quote a human can check in ten seconds is the whole point of the verification packet."
       },
       "design": {
        "type": "string",
        "enum": [
         "rct",
         "controlled-trial",
         "cohort",
         "case-series",
         "case-report",
         "meta-analysis",
         "animal-controlled",
         "animal-observational",
         "in-vitro",
         "observational-human",
         "regulatory-decision",
         "registry-entry",
         "review",
         "abstract"
        ]
       },
       "n": {
        "type": "string"
       },
       "controls": {
        "type": "string"
       },
       "blinding": {
        "type": "string"
       },
       "randomisation": {
        "type": "string"
       },
       "note": {
        "type": "string"
       }
      }
     }
    },
    "rung": {
     "$ref": "common.schema.json#/$defs/rung"
    },
    "grounding": {
     "$ref": "common.schema.json#/$defs/grounding"
    },
    "replication": {
     "type": "object",
     "properties": {
      "independentGroups": {
       "type": "integer",
       "minimum": 0
      },
      "note": {
       "type": "string",
       "description": "Must say plainly when replication does NOT hold."
      }
     }
    },
    "status": {
     "type": "object",
     "properties": {
      "peerReviewed": {
       "type": "boolean"
      },
      "preprint": {
       "type": "boolean"
      },
      "retracted": {
       "type": "boolean"
      },
      "contradicted": {
       "type": "boolean"
      }
     }
    },
    "supports": {
     "$ref": "common.schema.json#/$defs/idList",
     "description": "Capabilities or goals this claim is evidence FOR."
    },
    "contradicts": {
     "$ref": "common.schema.json#/$defs/idList",
     "description": "Claims or capabilities this claim is evidence AGAINST (including null results)."
    },
    "replicates": {
     "$ref": "common.schema.json#/$defs/idList"
    },
    "drift": {
     "type": "string",
     "description": "Demonstrated vs commonly claimed."
    },
    "wouldMove": {
     "type": "string"
    },
    "limitations": {
     "type": "array",
     "items": {
      "type": "string"
     }
    },
    "provenance": {
     "$ref": "common.schema.json#/$defs/provenance"
    },
    "review": {
     "$ref": "common.schema.json#/$defs/review"
    }
   }
  },
  "common.schema.json": {
   "$schema": "https://json-schema.org/draft/2020-12/schema",
   "$id": "https://humanrepairmap.com/schema/common.schema.json",
   "title": "Human Repair Graph — shared definitions",
   "description": "Definitions every record type reuses: identifiers, the evidence ladder, provenance and review. Records are validated by scripts/build.mjs against these schemas; the schemas are also served at /api/schema so a client can validate what it is about to propose.",
   "$defs": {
    "id": {
     "type": "string",
     "pattern": "^hrm:(goal|capability|question|claim|experiment|source|cell|route|prediction)/[a-z0-9]+(-[a-z0-9]+)*(--[a-z0-9]+(-[a-z0-9]+)*)?$",
     "description": "hrm:<type>/<slug>. Never renamed; see ontology/mappings.json."
    },
    "idList": {
     "type": "array",
     "items": {
      "$ref": "#/$defs/id"
     },
     "uniqueItems": true
    },
    "rung": {
     "type": "string",
     "enum": [
      "L0",
      "L1",
      "L2",
      "L3",
      "L4",
      "L5"
     ],
     "description": "L0 proposed · L1 in a dish · L2 in a rodent · L3 in a large animal · L4 in humans, once · L5 in humans, independently. See records/rubrics.json."
    },
    "grounding": {
     "type": "string",
     "enum": [
      "G0",
      "G1",
      "G2",
      "G3",
      "G4"
     ],
     "description": "G0 assertion (cannot enter the map) · G1 cited text · G2 structured record · G3 primary data · G4 instrument-signed."
    },
    "measured": {
     "type": "string",
     "enum": [
      "function",
      "biomarker",
      "opening",
      "transduction",
      "access",
      "structure",
      "none",
      "unspecified"
     ],
     "description": "What actually changed: a life (function), a surrogate number (biomarker), a barrier opened, cells transduced, a compartment accessed, an anatomical structure formed, or nothing demonstrated. unspecified is reserved for grid capabilities derived from v0.2 cell records, which did not record it."
    },
    "blocked": {
     "type": "string",
     "enum": [
      "science",
      "framework",
      "none"
     ]
    },
    "capabilityClass": {
     "type": "string",
     "enum": [
      "see",
      "model",
      "reach",
      "edit",
      "verify",
      "control"
     ]
    },
    "primitive": {
     "type": "string",
     "enum": [
      "stop",
      "remove",
      "repair",
      "replace",
      "regenerate",
      "reconnect",
      "recalibrate",
      "preserve"
     ]
    },
    "projection": {
     "type": "string",
     "enum": [
      "universal-repair",
      "rejuvenation"
     ]
    },
    "date": {
     "type": "string",
     "pattern": "^\\d{4}-\\d{2}-\\d{2}$"
    },
    "requirementGroup": {
     "type": "object",
     "description": "Exactly one of all/any. {all:[...]} = every member needed; {any:[...]} = one suffices. Groups on a record are ANDed.",
     "oneOf": [
      {
       "required": [
        "all"
       ],
       "properties": {
        "all": {
         "$ref": "#/$defs/idList",
         "minItems": 1
        },
        "note": {
         "type": "string"
        }
       },
       "additionalProperties": false
      },
      {
       "required": [
        "any"
       ],
       "properties": {
        "any": {
         "$ref": "#/$defs/idList",
         "minItems": 2
        },
        "note": {
         "type": "string"
        }
       },
       "additionalProperties": false
      }
     ]
    },
    "actor": {
     "type": "object",
     "required": [
      "type",
      "name"
     ],
     "properties": {
      "type": {
       "type": "string",
       "enum": [
        "human",
        "ai",
        "import"
       ]
      },
      "name": {
       "type": "string",
       "minLength": 1
      },
      "model": {
       "type": "string",
       "description": "Required when type is ai: the model id, e.g. claude-fable-5-1."
      },
      "version": {
       "type": "string"
      },
      "orcid": {
       "type": "string",
       "pattern": "^\\d{4}-\\d{4}-\\d{4}-\\d{3}[0-9X]$"
      },
      "session": {
       "type": "string",
       "description": "Session or run identifier so a batch of proposals can be traced and, if needed, withdrawn together."
      }
     },
     "if": {
      "properties": {
       "type": {
        "const": "ai"
       }
      }
     },
     "then": {
      "required": [
       "model"
      ]
     }
    },
    "provenance": {
     "type": "object",
     "required": [
      "proposedBy",
      "method",
      "date"
     ],
     "properties": {
      "proposedBy": {
       "$ref": "#/$defs/actor"
      },
      "method": {
       "type": "string",
       "description": "How it was produced: 'manual reasoning from the cited sources', 'derived from records/cells by build.mjs', 'extracted by <model> from <source> with schema v0.3', ..."
      },
      "date": {
       "$ref": "#/$defs/date"
      },
      "evidenceAccessed": {
       "$ref": "#/$defs/idList",
       "description": "Source ids the proposer actually consulted."
      },
      "extraction": {
       "type": "object",
       "description": "Present when a model extracted the record from a document.",
       "properties": {
        "model": {
         "type": "string"
        },
        "schemaVersion": {
         "type": "string"
        },
        "prompt": {
         "type": "string"
        },
        "timestamp": {
         "type": "string"
        }
       }
      }
     }
    },
    "review": {
     "type": "object",
     "required": [
      "state"
     ],
     "properties": {
      "state": {
       "type": "string",
       "enum": [
        "ai-proposed",
        "submitted",
        "in-review",
        "reviewed",
        "disputed",
        "superseded"
       ]
      },
      "reviewedBy": {
       "type": "string",
       "description": "A named human. Required when state is reviewed."
      },
      "date": {
       "$ref": "#/$defs/date"
      },
      "checks": {
       "type": "array",
       "items": {
        "type": "object",
        "required": [
         "id",
         "by",
         "date"
        ],
        "properties": {
         "id": {
          "type": "string",
          "enum": [
           "source-resolved",
           "cross-checked",
           "human-opened-source",
           "independently-replicated"
          ]
         },
         "by": {
          "type": "string"
         },
         "date": {
          "$ref": "#/$defs/date"
         },
         "note": {
          "type": "string"
         }
        }
       }
      },
      "history": {
       "type": "array",
       "items": {
        "type": "object",
        "required": [
         "from",
         "to",
         "by",
         "date"
        ],
        "properties": {
         "from": {
          "type": "string"
         },
         "to": {
          "type": "string"
         },
         "by": {
          "type": "string"
         },
         "date": {
          "$ref": "#/$defs/date"
         },
         "note": {
          "type": "string"
         }
        }
       }
      },
      "supersededBy": {
       "$ref": "#/$defs/id"
      }
     },
     "if": {
      "properties": {
       "state": {
        "const": "reviewed"
       }
      }
     },
     "then": {
      "required": [
       "reviewedBy"
      ]
     }
    }
   }
  },
  "experiment.schema.json": {
   "$schema": "https://json-schema.org/draft/2020-12/schema",
   "$id": "https://humanrepairmap.com/schema/experiment.schema.json",
   "title": "Experiment",
   "description": "A candidate or completed study that TESTS one or more questions. Feasibility is expressed in classes (low/medium/high; weeks/months/years) because a dollar figure the map cannot source would be exactly the kind of confident number it refuses to print elsewhere.",
   "type": "object",
   "required": [
    "id",
    "type",
    "name",
    "tests",
    "design",
    "status",
    "provenance",
    "review"
   ],
   "additionalProperties": false,
   "properties": {
    "id": {
     "$ref": "common.schema.json#/$defs/id"
    },
    "type": {
     "const": "experiment"
    },
    "name": {
     "type": "string",
     "minLength": 5,
     "maxLength": 200
    },
    "tests": {
     "$ref": "common.schema.json#/$defs/idList",
     "description": "Question ids. At least one."
    },
    "design": {
     "type": "object",
     "required": [
      "species",
      "intervention",
      "readout"
     ],
     "properties": {
      "species": {
       "type": "string"
      },
      "model": {
       "type": "string"
      },
      "intervention": {
       "type": "string"
      },
      "comparator": {
       "type": "string"
      },
      "readout": {
       "type": "string",
       "description": "The measurement that discriminates the hypotheses."
      },
      "duration": {
       "type": "string"
      },
      "n": {
       "type": "string"
      }
     }
    },
    "discriminates": {
     "type": "string",
     "description": "Which hypothesis each outcome would favour. An experiment whose every outcome is compatible with every hypothesis is not one."
    },
    "feasibility": {
     "type": "object",
     "properties": {
      "costClass": {
       "type": "string",
       "enum": [
        "low",
        "medium",
        "high"
       ]
      },
      "durationClass": {
       "type": "string",
       "enum": [
        "weeks",
        "months",
        "years"
       ]
      },
      "requires": {
       "type": "array",
       "items": {
        "type": "string"
       },
       "description": "Capabilities, models, equipment or approvals needed."
      },
      "ethics": {
       "type": "string"
      }
     }
    },
    "status": {
     "type": "string",
     "enum": [
      "proposed",
      "registered",
      "running",
      "completed",
      "abandoned"
     ]
    },
    "registration": {
     "type": "string",
     "description": "NCT id, protocols.io DOI, preregistration URL."
    },
    "results": {
     "$ref": "common.schema.json#/$defs/idList",
     "description": "Claim ids produced by this experiment, including null results."
    },
    "provenance": {
     "$ref": "common.schema.json#/$defs/provenance"
    },
    "review": {
     "$ref": "common.schema.json#/$defs/review"
    }
   }
  },
  "goal.schema.json": {
   "$schema": "https://json-schema.org/draft/2020-12/schema",
   "$id": "https://humanrepairmap.com/schema/goal.schema.json",
   "title": "Goal",
   "description": "A repair outcome stated from the person's side: 'scarless functional repair of adult skin after full-thickness injury'. Goals decompose (requires) into sub-goals and capabilities with AND/OR groups. The two public maps are projections of the goal tree; a goal may sit in both.",
   "type": "object",
   "required": [
    "id",
    "type",
    "name",
    "description",
    "projections",
    "provenance",
    "review"
   ],
   "additionalProperties": false,
   "properties": {
    "id": {
     "$ref": "common.schema.json#/$defs/id"
    },
    "type": {
     "const": "goal"
    },
    "name": {
     "type": "string",
     "minLength": 3,
     "maxLength": 160
    },
    "description": {
     "type": "string",
     "minLength": 20
    },
    "projections": {
     "type": "array",
     "items": {
      "$ref": "common.schema.json#/$defs/projection"
     },
     "minItems": 1,
     "uniqueItems": true
    },
    "parent": {
     "$ref": "common.schema.json#/$defs/id",
     "description": "The goal this one is part of, for tree rendering. Dependency is carried by requires, not by parent."
    },
    "requires": {
     "type": "array",
     "items": {
      "$ref": "common.schema.json#/$defs/requirementGroup"
     }
    },
    "blockedBy": {
     "$ref": "common.schema.json#/$defs/idList"
    },
    "testSuite": {
     "type": "array",
     "description": "Concrete scenarios a general capability must pass to count as general for this goal ('small skin wound', 'compound fracture', ...). A checklist, not a grade.",
     "items": {
      "type": "object",
      "required": [
       "scenario"
      ],
      "properties": {
       "scenario": {
        "type": "string"
       },
       "state": {
        "type": "string",
        "enum": [
         "routine",
         "partial",
         "unsolved"
        ]
       },
       "note": {
        "type": "string"
       }
      }
     }
    },
    "existenceProof": {
     "type": "string",
     "description": "Where nature or a narrow clinical case already does this (fetal skin, spiny mouse, oral mucosa) — the reason the goal is not known to be impossible."
    },
    "informationLimited": {
     "type": "boolean"
    },
    "provenance": {
     "$ref": "common.schema.json#/$defs/provenance"
    },
    "review": {
     "$ref": "common.schema.json#/$defs/review"
    }
   }
  },
  "prediction.schema.json": {
   "$schema": "https://json-schema.org/draft/2020-12/schema",
   "$id": "https://humanrepairmap.com/schema/prediction.schema.json",
   "title": "Prediction",
   "description": "A locked forecast about a question, claim or capability, made by a named human or a named model version BEFORE the outcome is known, and resolved later against reality. This is how the map becomes a prospective, contamination-free benchmark for scientific reasoning: the world produces the test set. Registered through POST /api/predictions or the MCP tool register_prediction; the registration is hash-chained in the public event log and cannot be edited afterwards.",
   "type": "object",
   "required": [
    "subject",
    "statement",
    "probability",
    "resolutionCriteria",
    "horizon",
    "predictor"
   ],
   "additionalProperties": false,
   "properties": {
    "id": {
     "$ref": "common.schema.json#/$defs/id"
    },
    "type": {
     "const": "prediction"
    },
    "subject": {
     "$ref": "common.schema.json#/$defs/id",
     "description": "The question, claim or capability the forecast is about."
    },
    "statement": {
     "type": "string",
     "minLength": 15,
     "maxLength": 600,
     "description": "What will be observed, stated so that a stranger can later say yes or no."
    },
    "probability": {
     "type": "number",
     "minimum": 0,
     "maximum": 1
    },
    "resolutionCriteria": {
     "type": "string",
     "minLength": 15,
     "description": "Exactly what evidence counts as resolving it true or false. Vague criteria make the prediction void, not right."
    },
    "horizon": {
     "$ref": "common.schema.json#/$defs/date",
     "description": "Date by which it should be resolvable."
    },
    "predictor": {
     "$ref": "common.schema.json#/$defs/actor"
    },
    "evidenceAccessed": {
     "$ref": "common.schema.json#/$defs/idList",
     "description": "What the predictor consulted. A model should list the node ids it read."
    },
    "reasoning": {
     "type": "string",
     "maxLength": 4000,
     "description": "Structured reasoning, kept with the prediction so that calibration can later be studied per method, not just per model."
    },
    "graphSnapshot": {
     "type": "string",
     "description": "The snapshot version the predictor saw (from /api/graph/manifest). Filled by the server."
    },
    "registeredAt": {
     "type": "string",
     "description": "Server-assigned ISO timestamp."
    },
    "state": {
     "type": "string",
     "enum": [
      "open",
      "resolved-true",
      "resolved-false",
      "void"
     ]
    },
    "resolution": {
     "type": "object",
     "properties": {
      "by": {
       "type": "string"
      },
      "date": {
       "$ref": "common.schema.json#/$defs/date"
      },
      "outcomeSource": {
       "$ref": "common.schema.json#/$defs/id"
      },
      "note": {
       "type": "string"
      }
     },
     "description": "Only a steward may write this, and only by appending an event."
    }
   }
  },
  "question.schema.json": {
   "$schema": "https://json-schema.org/draft/2020-12/schema",
   "$id": "https://humanrepairmap.com/schema/question.schema.json",
   "title": "Question",
   "description": "An unresolved uncertainty whose answer would change a grade or a dependency. The unit of research prioritisation: every '?' in the map is one of these, and the ranking the API returns is computed from what a question blocks, never from an invented probability.",
   "type": "object",
   "required": [
    "id",
    "type",
    "question",
    "why",
    "blocks",
    "state",
    "provenance",
    "review"
   ],
   "additionalProperties": false,
   "properties": {
    "id": {
     "$ref": "common.schema.json#/$defs/id"
    },
    "type": {
     "const": "question"
    },
    "question": {
     "type": "string",
     "minLength": 15,
     "maxLength": 400
    },
    "why": {
     "type": "string",
     "minLength": 20,
     "description": "What changes if it is answered — which grade moves, which dependency resolves."
    },
    "blocks": {
     "$ref": "common.schema.json#/$defs/idList",
     "description": "Capabilities or goals gated by this question. Drives the ranking."
    },
    "hypotheses": {
     "type": "array",
     "items": {
      "type": "string"
     },
     "description": "The live competing answers, so an experiment can be judged on whether it discriminates between them."
    },
    "knownUnknowns": {
     "type": "array",
     "items": {
      "type": "string"
     }
    },
    "whatWouldResolve": {
     "type": "string",
     "description": "The observation that would settle it — stated so a reader can recognise it when it appears."
    },
    "state": {
     "type": "string",
     "enum": [
      "open",
      "resolved",
      "superseded"
     ]
    },
    "resolvedBy": {
     "$ref": "common.schema.json#/$defs/idList",
     "description": "Claim ids. Non-empty only when state is resolved."
    },
    "projections": {
     "type": "array",
     "items": {
      "$ref": "common.schema.json#/$defs/projection"
     },
     "uniqueItems": true
    },
    "provenance": {
     "$ref": "common.schema.json#/$defs/provenance"
    },
    "review": {
     "$ref": "common.schema.json#/$defs/review"
    }
   }
  },
  "source.schema.json": {
   "$schema": "https://json-schema.org/draft/2020-12/schema",
   "$id": "https://humanrepairmap.com/schema/source.schema.json",
   "title": "Source",
   "description": "Where a claim's evidence lives. Two separate facts are recorded and must never be conflated: resolution (a machine confirmed the source exists and its metadata matches — scripts/resolve-sources.mjs) and humanOpened (a named person read it). Resolved is not reviewed.",
   "type": "object",
   "required": [
    "id",
    "type",
    "citation",
    "kind",
    "year",
    "resolution",
    "provenance"
   ],
   "additionalProperties": false,
   "properties": {
    "id": {
     "$ref": "common.schema.json#/$defs/id"
    },
    "type": {
     "const": "source"
    },
    "citation": {
     "type": "string",
     "minLength": 10,
     "description": "Human-readable: first author et al., journal, year."
    },
    "title": {
     "type": "string"
    },
    "authors": {
     "type": "string"
    },
    "venue": {
     "type": "string"
    },
    "year": {
     "type": "integer",
     "minimum": 1800,
     "maximum": 2100
    },
    "kind": {
     "type": "string",
     "enum": [
      "article",
      "preprint",
      "abstract",
      "regulatory",
      "registry",
      "dataset",
      "protocol",
      "book",
      "letter",
      "report",
      "web"
     ]
    },
    "doi": {
     "type": "string",
     "pattern": "^10\\.\\d{4,9}/\\S+$"
    },
    "pmid": {
     "type": "string",
     "pattern": "^\\d{1,9}$"
    },
    "pmcid": {
     "type": "string",
     "pattern": "^PMC\\d+$"
    },
    "nct": {
     "type": "string",
     "pattern": "^NCT\\d{8}$"
    },
    "url": {
     "type": "string",
     "pattern": "^https?://"
    },
    "license": {
     "type": "string"
    },
    "openAccess": {
     "type": "boolean"
    },
    "resolution": {
     "type": "object",
     "required": [
      "resolved"
     ],
     "additionalProperties": false,
     "properties": {
      "resolved": {
       "type": "boolean",
       "description": "A machine located the record and its metadata matched (title/venue/year). False until scripts/resolve-sources.mjs has run for it."
      },
      "checkedOn": {
       "$ref": "common.schema.json#/$defs/date"
      },
      "via": {
       "type": "string",
       "enum": [
        "crossref",
        "pubmed",
        "clinicaltrials",
        "manual",
        "none"
       ]
      },
      "metadataMatches": {
       "type": "boolean"
      },
      "resolvedTitle": {
       "type": "string"
      },
      "note": {
       "type": "string"
      }
     }
    },
    "humanOpened": {
     "type": "object",
     "required": [
      "by",
      "date"
     ],
     "properties": {
      "by": {
       "type": "string"
      },
      "date": {
       "$ref": "common.schema.json#/$defs/date"
      },
      "note": {
       "type": "string"
      }
     },
     "description": "Only a named human may write this."
    },
    "note": {
     "type": "string"
    },
    "provenance": {
     "$ref": "common.schema.json#/$defs/provenance"
    }
   }
  }
 },
 "nodes": [
  {
   "type": "capability",
   "id": "hrm:capability/acute-wound-infection-control",
   "name": "Prevent and treat acute wound infection",
   "class": "control",
   "primitive": "remove",
   "projections": [
    "universal-repair"
   ],
   "description": "Debride contaminated tissue and eliminate planktonic pathogens from an acute wound so healing can proceed.",
   "target": {
    "node": "hrm:cell/microbiome"
   },
   "grade": {
    "basis": "standard-of-care",
    "rung": "L5",
    "measured": "function",
    "blocked": "none",
    "note": "Surgical debridement, irrigation and systemic or topical antimicrobials are routine and effective for acute wounds. Antimicrobial resistance erodes this capability over time and is not graded here."
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-contamination-control"
    ]
   }
  },
  {
   "id": "hrm:capability/adipocyte--edit",
   "type": "capability",
   "derived": true,
   "name": "Adipocyte: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Adipocyte.",
   "target": {
    "node": "hrm:cell/adipocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Incretin drugs change mass by changing behaviour and metabolism, not by editing cells."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/adipocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/adipocyte--model",
   "type": "capability",
   "derived": true,
   "name": "Adipocyte: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Adipocyte.",
   "target": {
    "node": "hrm:cell/adipocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Healthy adiposity varies enormously between individuals."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/adipocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/adipocyte--reach",
   "type": "capability",
   "derived": true,
   "name": "Adipocyte: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Adipocyte.",
   "target": {
    "node": "hrm:cell/adipocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Accessible by volume but not specifically targetable."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/adipocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/adipocyte--see",
   "type": "capability",
   "derived": true,
   "name": "Adipocyte: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Adipocyte.",
   "target": {
    "node": "hrm:cell/adipocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "MRI and DEXA quantify fat depots precisely and non-invasively."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/adipocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/adipocyte--verify",
   "type": "capability",
   "derived": true,
   "name": "Adipocyte: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Adipocyte.",
   "target": {
    "node": "hrm:cell/adipocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Mass and distribution are easy to measure."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/adipocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/alveolar-epithelium--edit",
   "type": "capability",
   "derived": true,
   "name": "Alveolar epithelium: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Alveolar epithelium.",
   "target": {
    "node": "hrm:cell/alveolar-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Inhaled mRNA and gene editing for CF are in early trials. Modulators treat protein, not cells."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/alveolar-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/alveolar-epithelium--model",
   "type": "capability",
   "derived": true,
   "name": "Alveolar epithelium: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Alveolar epithelium.",
   "target": {
    "node": "hrm:cell/alveolar-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Alveolar architecture, once destroyed, is not re-formed."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/alveolar-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/alveolar-epithelium--reach",
   "type": "capability",
   "derived": true,
   "name": "Alveolar epithelium: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Alveolar epithelium.",
   "target": {
    "node": "hrm:cell/alveolar-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Inhalation delivers to airway surface; alveolar and basal cell targeting is inefficient."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/alveolar-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/alveolar-epithelium--see",
   "type": "capability",
   "derived": true,
   "name": "Alveolar epithelium: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Alveolar epithelium.",
   "target": {
    "node": "hrm:cell/alveolar-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "CT shows architecture; bronchoscopy samples focally. No cell-state map."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/alveolar-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/alveolar-epithelium--verify",
   "type": "capability",
   "derived": true,
   "name": "Alveolar epithelium: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Alveolar epithelium.",
   "target": {
    "node": "hrm:cell/alveolar-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Spirometry is a good functional readout."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/alveolar-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
   "name": "Build appendage-bearing human skin from pluripotent stem cells",
   "class": "edit",
   "primitive": "replace",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Generate, from human pluripotent stem cells, a skin construct with stratified epidermis, dermis, pigmented hair follicles, sebaceous glands and sensory neurons that forms planar hair-bearing skin when grafted.",
   "target": {
    "node": "hrm:cell/tissue-architecture"
   },
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "structure",
    "blocked": "science",
    "note": "Human pluripotent stem-cell skin organoids (4–5 months in culture) form epidermis, fat-rich dermis, pigmented hair follicles with sebaceous glands and Merkel-targeting sensory neurons, and form planar hair-bearing skin when grafted onto nude mice (Lee 2020). Human cells, mouse host, one group. Nothing grafted into a person."
   },
   "blockedBy": [
    "hrm:question/organised-microvasculature-in-thick-regenerated-tissue",
    "hrm:question/pluripotent-derived-skin-engrafts-in-humans"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/lee-2020-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/established-scar-repair",
     "hrm:goal/skin-structural-reconstruction"
    ],
    "blockedBy": [
     "hrm:question/pluripotent-derived-skin-engrafts-in-humans",
     "hrm:question/organised-microvasculature-in-thick-regenerated-tissue"
    ],
    "supportedBy": [
     "hrm:claim/hpsc-skin-organoids-form-hair-bearing-skin-in-mice"
    ]
   }
  },
  {
   "id": "hrm:capability/beta-cell--edit",
   "type": "capability",
   "derived": true,
   "name": "Pancreatic islet β-cell: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Pancreatic islet β-cell.",
   "target": {
    "node": "hrm:cell/beta-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Stem-cell-derived islets produced insulin independence in early trials, but require immunosuppression."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/beta-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/beta-cell--model",
   "type": "capability",
   "derived": true,
   "name": "Pancreatic islet β-cell: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Pancreatic islet β-cell.",
   "target": {
    "node": "hrm:cell/beta-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Glucose control gives a clear functional target."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/beta-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/beta-cell--reach",
   "type": "capability",
   "derived": true,
   "name": "Pancreatic islet β-cell: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Pancreatic islet β-cell.",
   "target": {
    "node": "hrm:cell/beta-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Pancreas is deep, diffuse and enzymatically hostile; islets are a tiny fraction of tissue."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/beta-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/beta-cell--see",
   "type": "capability",
   "derived": true,
   "name": "Pancreatic islet β-cell: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Pancreatic islet β-cell.",
   "target": {
    "node": "hrm:cell/beta-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "THE binding gap: there is no clinical way to measure β-cell mass in a living person."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/beta-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/beta-cell--verify",
   "type": "capability",
   "derived": true,
   "name": "Pancreatic islet β-cell: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Pancreatic islet β-cell.",
   "target": {
    "node": "hrm:cell/beta-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "C-peptide and continuous glucose monitoring are good functional readouts."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/beta-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/bone-cell--edit",
   "type": "capability",
   "derived": true,
   "name": "Osteoblast / osteoclast: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Osteoblast / osteoclast.",
   "target": {
    "node": "hrm:cell/bone-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Pharmacological modulation, not cell repair or replacement."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/bone-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/bone-cell--model",
   "type": "capability",
   "derived": true,
   "name": "Osteoblast / osteoclast: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Osteoblast / osteoclast.",
   "target": {
    "node": "hrm:cell/bone-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Bone remodelling balance is well understood."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/bone-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/bone-cell--reach",
   "type": "capability",
   "derived": true,
   "name": "Osteoblast / osteoclast: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Osteoblast / osteoclast.",
   "target": {
    "node": "hrm:cell/bone-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Bisphosphonates and denosumab reach and modulate these cells effectively."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/bone-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/bone-cell--see",
   "type": "capability",
   "derived": true,
   "name": "Osteoblast / osteoclast: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Osteoblast / osteoclast.",
   "target": {
    "node": "hrm:cell/bone-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "DEXA measures density, not cell activity; turnover markers are indirect."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/bone-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/bone-cell--verify",
   "type": "capability",
   "derived": true,
   "name": "Osteoblast / osteoclast: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Osteoblast / osteoclast.",
   "target": {
    "node": "hrm:cell/bone-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "DEXA and fracture incidence are solid endpoints."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/bone-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/cancer-risk-control-under-rejuvenation",
   "name": "Keep cancer risk acceptable while rejuvenating tissue",
   "class": "control",
   "primitive": "preserve",
   "projections": [
    "rejuvenation"
   ],
   "description": "Rejuvenation makes cells more plastic and proliferative — the territory cancer exploits. Bound that risk in aged humans, over repeated treatment, with a stopping rule.",
   "grade": {
    "basis": "ungraded",
    "note": "No grade: the human evidence does not exist and the seed did not grade the mouse tumorigenicity literature. The node exists because the goal cannot be reached without it."
   },
   "blockedBy": [
    "hrm:question/cancer-risk-of-repeated-partial-reprogramming"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/systemic-rejuvenation"
    ],
    "blockedBy": [
     "hrm:question/cancer-risk-of-repeated-partial-reprogramming"
    ]
   }
  },
  {
   "id": "hrm:capability/cardiomyocyte--edit",
   "type": "capability",
   "derived": true,
   "name": "Cardiomyocyte: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Cardiomyocyte.",
   "target": {
    "node": "hrm:cell/cardiomyocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "No approved cardiomyocyte-directed therapy. Scar replaces muscle faster than regeneration."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cardiomyocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cardiomyocyte--model",
   "type": "capability",
   "derived": true,
   "name": "Cardiomyocyte: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Cardiomyocyte.",
   "target": {
    "node": "hrm:cell/cardiomyocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Zebrafish and neonatal mice regenerate heart muscle, so a target state exists — not in adult humans."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cardiomyocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cardiomyocyte--reach",
   "type": "capability",
   "derived": true,
   "name": "Cardiomyocyte: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Cardiomyocyte.",
   "target": {
    "node": "hrm:cell/cardiomyocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "AAV9 has useful cardiac tropism; trials in Danon disease and cardiomyopathy are running."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cardiomyocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cardiomyocyte--see",
   "type": "capability",
   "derived": true,
   "name": "Cardiomyocyte: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Cardiomyocyte.",
   "target": {
    "node": "hrm:cell/cardiomyocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Echo and MRI measure function; troponin reports death. Cell state is invisible in vivo."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cardiomyocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cardiomyocyte--verify",
   "type": "capability",
   "derived": true,
   "name": "Cardiomyocyte: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Cardiomyocyte.",
   "target": {
    "node": "hrm:cell/cardiomyocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Ejection fraction and imaging; no cell-level confirmation."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cardiomyocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/cell-identity-retention-under-partial-reprogramming",
   "name": "Rejuvenate cells while they keep their identity",
   "class": "model",
   "primitive": "preserve",
   "projections": [
    "rejuvenation"
   ],
   "description": "Drive a cell's epigenetic state younger without pushing it toward pluripotency: the cell stays a retinal ganglion cell, a hepatocyte, a neuron with its connections.",
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "structure",
    "blocked": "science",
    "note": "Short cyclic OSKM in mice ameliorated aging hallmarks without teratoma formation, i.e. without full dedifferentiation (Ocampo 2016); OSK without c-Myc in retinal ganglion cells restored function with identity retained (Lu 2020). Mouse; the safe expression window in humans is unknown."
   },
   "blockedBy": [
    "hrm:question/partial-reprogramming-human-safety"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/ocampo-2016-cell",
     "hrm:source/lu-2020-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/systemic-rejuvenation"
    ],
    "blockedBy": [
     "hrm:question/partial-reprogramming-human-safety"
    ],
    "supportedBy": [
     "hrm:claim/cyclic-partial-reprogramming-ameliorates-aging-in-mice",
     "hrm:claim/osk-reprogramming-restores-vision-in-mice"
    ]
   }
  },
  {
   "id": "hrm:capability/chondrocyte--edit",
   "type": "capability",
   "derived": true,
   "name": "Chondrocyte (articular cartilage): edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Chondrocyte (articular cartilage).",
   "target": {
    "node": "hrm:cell/chondrocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "MACI is approved but yields mechanically inferior fibrocartilage, not hyaline."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/chondrocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/chondrocyte--model",
   "type": "capability",
   "derived": true,
   "name": "Chondrocyte (articular cartilage): model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Chondrocyte (articular cartilage).",
   "target": {
    "node": "hrm:cell/chondrocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Hyaline cartilage is a clear target that repair never produces."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/chondrocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/chondrocyte--reach",
   "type": "capability",
   "derived": true,
   "name": "Chondrocyte (articular cartilage): reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Chondrocyte (articular cartilage).",
   "target": {
    "node": "hrm:cell/chondrocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Avascular: no blood supply to deliver through. Intra-articular injection is the only route."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/chondrocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/chondrocyte--see",
   "type": "capability",
   "derived": true,
   "name": "Chondrocyte (articular cartilage): see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Chondrocyte (articular cartilage).",
   "target": {
    "node": "hrm:cell/chondrocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "MRI images cartilage thickness and defects well."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/chondrocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/chondrocyte--verify",
   "type": "capability",
   "derived": true,
   "name": "Chondrocyte (articular cartilage): verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Chondrocyte (articular cartilage).",
   "target": {
    "node": "hrm:cell/chondrocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "MRI and function scores."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/chondrocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/chronic-wound-biofilm-eradication",
   "name": "Eradicate established biofilm in a chronic wound",
   "class": "control",
   "primitive": "remove",
   "projections": [
    "universal-repair"
   ],
   "description": "Reliably clear a mature polymicrobial biofilm from a chronic wound bed so that a stalled wound can progress to closure.",
   "target": {
    "node": "hrm:cell/microbiome"
   },
   "grade": {
    "basis": "ungraded",
    "note": "Placed so the gap is visible. The literature on biofilm-directed therapy in chronic wounds was not searched in this seed; grading it is the first open task on this node."
   },
   "blockedBy": [
    "hrm:question/reliable-biofilm-eradication-in-chronic-wounds"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-contamination-control"
    ],
    "blockedBy": [
     "hrm:question/reliable-biofilm-eradication-in-chronic-wounds"
    ]
   }
  },
  {
   "id": "hrm:capability/cns-neuron--edit",
   "type": "capability",
   "derived": true,
   "name": "Central neuron: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Central neuron.",
   "target": {
    "node": "hrm:cell/cns-neuron"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Nusinersen treats a spinal motor-neuron disease. No neuron has been replaced in a human."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cns-neuron.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cns-neuron--model",
   "type": "capability",
   "derived": true,
   "name": "Central neuron: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Central neuron.",
   "target": {
    "node": "hrm:cell/cns-neuron"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "The substrate is identity — a healthy target state cannot be specified without specifying the person."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cns-neuron.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cns-neuron--reach",
   "type": "capability",
   "derived": true,
   "name": "Central neuron: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Central neuron.",
   "target": {
    "node": "hrm:cell/cns-neuron"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Intrathecal delivery reaches spinal cord; nothing reaches brain broadly. See the CNS delivery module."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cns-neuron.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/systemic-rejuvenation"
    ],
    "supportedBy": [
     "hrm:route/aav9",
     "hrm:route/bihtfr1",
     "hrm:route/brineura",
     "hrm:route/capsid",
     "hrm:route/cart",
     "hrm:route/ced",
     "hrm:route/denali",
     "hrm:route/exosomes",
     "hrm:route/fus",
     "hrm:route/intranasal",
     "hrm:route/jcr",
     "hrm:route/kebilidi",
     "hrm:route/lnp",
     "hrm:route/nusinersen",
     "hrm:route/roche",
     "hrm:route/tofersen"
    ]
   }
  },
  {
   "id": "hrm:capability/cns-neuron--see",
   "type": "capability",
   "derived": true,
   "name": "Central neuron: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Central neuron.",
   "target": {
    "node": "hrm:cell/cns-neuron"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Imaging and CSF markers are indirect. No single-cell state in a living brain."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cns-neuron.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cns-neuron--verify",
   "type": "capability",
   "derived": true,
   "name": "Central neuron: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Central neuron.",
   "target": {
    "node": "hrm:cell/cns-neuron"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Clinical scores and biomarkers; no direct confirmation of cell-level change."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cns-neuron.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cochlear-hair-cell--edit",
   "type": "capability",
   "derived": true,
   "name": "Cochlear hair cell: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Cochlear hair cell.",
   "target": {
    "node": "hrm:cell/cochlear-hair-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "OTOF gene therapy restored hearing in congenitally deaf children, 2024 trials. One genotype."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cochlear-hair-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cochlear-hair-cell--model",
   "type": "capability",
   "derived": true,
   "name": "Cochlear hair cell: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Cochlear hair cell.",
   "target": {
    "node": "hrm:cell/cochlear-hair-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Avian regeneration shows the target state exists biologically."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cochlear-hair-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cochlear-hair-cell--reach",
   "type": "capability",
   "derived": true,
   "name": "Cochlear hair cell: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Cochlear hair cell.",
   "target": {
    "node": "hrm:cell/cochlear-hair-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Intracochlear injection works but the cochlea is small, fluid-filled and easily damaged."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cochlear-hair-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cochlear-hair-cell--see",
   "type": "capability",
   "derived": true,
   "name": "Cochlear hair cell: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Cochlear hair cell.",
   "target": {
    "node": "hrm:cell/cochlear-hair-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Audiometry measures function, not cells. No way to image hair cells in a living human."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cochlear-hair-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/cochlear-hair-cell--verify",
   "type": "capability",
   "derived": true,
   "name": "Cochlear hair cell: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Cochlear hair cell.",
   "target": {
    "node": "hrm:cell/cochlear-hair-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Audiometry is precise and repeatable."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/cochlear-hair-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/corneal-epithelium--edit",
   "type": "capability",
   "derived": true,
   "name": "Corneal epithelium / limbal stem cell: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Corneal epithelium / limbal stem cell.",
   "target": {
    "node": "hrm:cell/corneal-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Holoclar, autologous limbal stem cells, EU 2015 — genuine tissue restoration."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/corneal-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/corneal-epithelium--model",
   "type": "capability",
   "derived": true,
   "name": "Corneal epithelium / limbal stem cell: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Corneal epithelium / limbal stem cell.",
   "target": {
    "node": "hrm:cell/corneal-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "A clear cornea is an unambiguous target state."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/corneal-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/corneal-epithelium--reach",
   "type": "capability",
   "derived": true,
   "name": "Corneal epithelium / limbal stem cell: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Corneal epithelium / limbal stem cell.",
   "target": {
    "node": "hrm:cell/corneal-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Surgically accessible; grafts placed directly."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/corneal-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/corneal-epithelium--see",
   "type": "capability",
   "derived": true,
   "name": "Corneal epithelium / limbal stem cell: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Corneal epithelium / limbal stem cell.",
   "target": {
    "node": "hrm:cell/corneal-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Slit lamp and OCT image it directly and non-invasively."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/corneal-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/corneal-epithelium--verify",
   "type": "capability",
   "derived": true,
   "name": "Corneal epithelium / limbal stem cell: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Corneal epithelium / limbal stem cell.",
   "target": {
    "node": "hrm:cell/corneal-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Corneal clarity and visual acuity."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/corneal-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/cutaneous-sensory-reinnervation",
   "name": "Restore sensory innervation of regenerated skin",
   "class": "edit",
   "primitive": "reconnect",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Regenerated or grafted skin regains touch, temperature and pain sensation comparable to uninjured skin, with nerve fibres reaching Merkel cells and follicles.",
   "target": {
    "node": "hrm:cell/peripheral-neuron"
   },
   "grade": {
    "basis": "claims",
    "rung": "L1",
    "measured": "structure",
    "blocked": "science",
    "note": "In a human tissue-engineered skin model, neurotrophic factors enhanced angiogenesis, coupling innervation to vascular growth in vitro (Blais 2013). Skin organoids form sensory nerve bundles targeting Merkel cells in culture (Lee 2020). Clinical experience that sensation in grafted skin recovers partially and slowly is common knowledge but is not sourced here, so it does not raise the rung."
   },
   "blockedBy": [
    "hrm:question/regenerated-skin-sensory-reinnervation"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/blais-2013-tissueeng",
     "hrm:source/lee-2020-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/established-scar-repair",
     "hrm:goal/skin-structural-reconstruction"
    ],
    "blockedBy": [
     "hrm:question/regenerated-skin-sensory-reinnervation"
    ],
    "supportedBy": [
     "hrm:claim/hpsc-skin-organoids-form-hair-bearing-skin-in-mice",
     "hrm:claim/neurotrophins-enhance-angiogenesis-in-engineered-skin"
    ]
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/dermal-adipocyte-regeneration",
   "name": "Regenerate dermal adipocytes in a healing wound",
   "class": "edit",
   "primitive": "regenerate",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Restore the dermal fat layer in a healed wound, including by converting scar-forming myofibroblasts back into adipocytes.",
   "target": {
    "node": "hrm:cell/adipocyte"
   },
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "structure",
    "blocked": "science",
    "note": "Myofibroblasts convert to adipocytes during wound-induced hair neogenesis in mice, dependent on follicle-derived BMP signalling (Plikus 2017). One group, mouse."
   },
   "blockedBy": [
    "hrm:question/dermal-adipocyte-regeneration-in-human-wounds"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/plikus-2017-science"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-structural-reconstruction"
    ],
    "blockedBy": [
     "hrm:question/dermal-adipocyte-regeneration-in-human-wounds"
    ],
    "supportedBy": [
     "hrm:claim/myofibroblasts-regenerate-adipocytes-in-mouse-wounds"
    ]
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/dermal-architecture-regeneration-without-scar",
   "name": "Regenerate dermis with appendages and no scar after full-thickness injury",
   "class": "edit",
   "primitive": "regenerate",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "After a full-thickness wound, produce new dermis whose collagen organisation, appendages and mechanical strength match uninjured skin, instead of a fibrotic scar.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "structure",
    "blocked": "science",
    "note": "In mice, blocking mechanotransduction (verteporfin, a YAP inhibitor, or fibroblast-specific YAP knockout) prevented Engrailed-1 activation and yielded wound regeneration with recovery of appendages, ultrastructure and mechanical strength (Mascharak 2021; one group). The default adult outcome in humans is scar (Gurtner 2008; Eming 2014). No large-animal or human evidence located.",
    "drift": "Covered as 'scarless healing drug found'; the demonstration is mouse dorsal skin, splinted, one laboratory."
   },
   "blockedBy": [
    "hrm:question/en1-inhibition-translates-to-human-skin"
   ],
   "wouldMove": "The same regenerative outcome (appendages plus native ultrastructure) in porcine or human skin, from an unaffiliated group.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/mascharak-2021-science",
     "hrm:source/gurtner-2008-nature",
     "hrm:source/eming-2014-scitranslmed"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-structural-reconstruction"
    ],
    "blockedBy": [
     "hrm:question/en1-inhibition-translates-to-human-skin"
    ],
    "contradictedBy": [
     "hrm:claim/adult-mammalian-wounds-heal-by-scar"
    ],
    "supportedBy": [
     "hrm:claim/yap-inhibition-yields-mouse-wound-regeneration"
    ]
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/dermal-substitute-for-chronic-wound-closure",
   "name": "Close a chronic wound with a bioengineered skin substitute",
   "class": "edit",
   "primitive": "replace",
   "projections": [
    "universal-repair"
   ],
   "description": "Apply a living, cell-containing bioengineered construct to a chronic ulcer and raise the rate of complete closure over standard care.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "function",
    "blocked": "none",
    "note": "Two different living constructs from two unaffiliated sponsors each raised complete closure of diabetic foot ulcers at 12 weeks in randomised multicentre trials: Graftskin 56% vs 38% (n=208, Veves 2001) and Dermagraft 30% vs 18% (n=314, Marston 2003). The constructs act as temporary biologic dressings that stimulate closure; they do not persist as the patient's dermis and regenerate no appendages.",
    "drift": "Marketed as 'skin equivalents'; what is proven is faster closure of ulcers, not equivalent skin."
   },
   "blockedBy": [
    "hrm:question/skin-substitutes-improve-scar-quality-not-just-closure"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/veves-2001-diabetescare",
     "hrm:source/marston-2003-diabetescare"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blockedBy": [
     "hrm:question/skin-substitutes-improve-scar-quality-not-just-closure"
    ],
    "supportedBy": [
     "hrm:claim/dermagraft-raises-diabetic-ulcer-closure",
     "hrm:claim/graftskin-raises-diabetic-ulcer-closure"
    ]
   }
  },
  {
   "id": "hrm:capability/endocrine-cell--edit",
   "type": "capability",
   "derived": true,
   "name": "Thyroid / adrenal endocrine cell: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Thyroid / adrenal endocrine cell.",
   "target": {
    "node": "hrm:cell/endocrine-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L1",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Nobody repairs these cells. Hormone replacement substitutes the output — permanently."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/endocrine-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/endocrine-cell--model",
   "type": "capability",
   "derived": true,
   "name": "Thyroid / adrenal endocrine cell: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Thyroid / adrenal endocrine cell.",
   "target": {
    "node": "hrm:cell/endocrine-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Target hormone ranges are well established."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/endocrine-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/endocrine-cell--reach",
   "type": "capability",
   "derived": true,
   "name": "Thyroid / adrenal endocrine cell: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Thyroid / adrenal endocrine cell.",
   "target": {
    "node": "hrm:cell/endocrine-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Small, deep, diffuse. Not specifically reachable."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/endocrine-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/endocrine-cell--see",
   "type": "capability",
   "derived": true,
   "name": "Thyroid / adrenal endocrine cell: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Thyroid / adrenal endocrine cell.",
   "target": {
    "node": "hrm:cell/endocrine-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Circulating hormone levels are near-ideal functional proxies."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/endocrine-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/endocrine-cell--verify",
   "type": "capability",
   "derived": true,
   "name": "Thyroid / adrenal endocrine cell: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Thyroid / adrenal endocrine cell.",
   "target": {
    "node": "hrm:cell/endocrine-cell"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Hormone assays are precise and cheap."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/endocrine-cell.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/endothelium--edit",
   "type": "capability",
   "derived": true,
   "name": "Vascular endothelium: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Vascular endothelium.",
   "target": {
    "node": "hrm:cell/endothelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "No endothelium-directed cell therapy. Risk factors are managed instead."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/endothelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/endothelium--model",
   "type": "capability",
   "derived": true,
   "name": "Vascular endothelium: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Vascular endothelium.",
   "target": {
    "node": "hrm:cell/endothelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Healthy endothelial phenotype is defined by behaviour, not a measurable set-point."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/endothelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/endothelium--reach",
   "type": "capability",
   "derived": true,
   "name": "Vascular endothelium: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Vascular endothelium.",
   "target": {
    "node": "hrm:cell/endothelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "The first cells anything intravenous touches."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/endothelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/endothelium--see",
   "type": "capability",
   "derived": true,
   "name": "Vascular endothelium: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Vascular endothelium.",
   "target": {
    "node": "hrm:cell/endothelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Function assessed indirectly by flow-mediated dilation; cell state inaccessible."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/endothelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/endothelium--verify",
   "type": "capability",
   "derived": true,
   "name": "Vascular endothelium: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Vascular endothelium.",
   "target": {
    "node": "hrm:cell/endothelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Functional proxies only."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/endothelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/epidermis-gene-corrected-stem-cell-replacement",
   "name": "Regenerate an entire epidermis from gene-corrected autologous stem cells",
   "class": "edit",
   "primitive": "repair",
   "projections": [
    "universal-repair"
   ],
   "description": "Correct a causal mutation in a patient's epidermal stem cells ex vivo and regenerate a durable, self-renewing, functional epidermis from them.",
   "target": {
    "node": "hrm:cell/keratinocyte"
   },
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "function",
    "blocked": "framework",
    "note": "Two patients with junctional epidermolysis bullosa (an adult, Mavilio 2006; a child with ~80% body surface regenerated, Hirsch 2017), both treated by the same group (De Luca, Modena). The biology has worked twice in one group; the rung stays L4 because no unaffiliated group has reproduced it. What stands between it and patients is manufacturing, regulatory path and disease rarity, with long-term integration-site safety an open scientific question.",
    "drift": "Reported as 'entire skin regenerated'; the regenerated organ is the epidermis, on a patient whose dermis was intact."
   },
   "blockedBy": [
    "hrm:question/gene-corrected-epidermal-graft-long-term-safety"
   ],
   "wouldMove": "An independent centre reproducing durable engraftment in a second inherited skin disease, with integration-site surveillance beyond five years.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/mavilio-2006-natmed",
     "hrm:source/hirsch-2017-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-structural-reconstruction"
    ],
    "blockedBy": [
     "hrm:question/gene-corrected-epidermal-graft-long-term-safety"
    ],
    "supportedBy": [
     "hrm:claim/transgenic-epidermal-stem-cells-regenerate-functional-epidermis-jeb"
    ]
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/epidermis-replacement-cultured-autograft",
   "name": "Replace lost epidermis with cultured autologous keratinocytes",
   "class": "edit",
   "primitive": "replace",
   "projections": [
    "universal-repair"
   ],
   "description": "Grow a patient's own keratinocytes into sheets and use them to permanently cover a large full-thickness skin loss.",
   "target": {
    "node": "hrm:cell/keratinocyte"
   },
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "function",
    "blocked": "none",
    "note": "Permanent coverage of large burns with cultured epithelial autografts was reported in 1984 (Gallico) and has since been used and followed long-term at unaffiliated centres (Sood 2000; reviewed in Sun 2014). The graft is epidermis only: no dermis, appendages or normal sensation, and the result is fragile skin.",
    "drift": "'Lab-grown skin' in headlines; what is grown is a thin epidermal sheet."
   },
   "wouldMove": "This capability is at the top rung for what it does; the missing capabilities are the dermal ones below it.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/gallico-1984-nejm",
     "hrm:source/sood-2000-jbcr",
     "hrm:source/sun-2014-science"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-structural-reconstruction"
    ],
    "supportedBy": [
     "hrm:claim/cultured-epithelial-autografts-permanently-cover-large-burns"
    ]
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/established-dermal-scar-reversal",
   "name": "Remodel an established scar into native dermis",
   "class": "edit",
   "primitive": "remove",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Convert a mature fibrotic dermal scar back into dermis with native matrix organisation and appendages — reversal, not prevention.",
   "target": {
    "node": "hrm:cell/extracellular-matrix"
   },
   "grade": {
    "basis": "claims",
    "rung": "L0",
    "measured": "none",
    "blocked": "science",
    "note": "No therapy reverses established fibrosis in any organ; approved antifibrotics slow progression (Henderson 2020, review). For dermal scar specifically, no reversal demonstration was located. The rung is L0 on the strength of a contradicting review, not an absence of search."
   },
   "blockedBy": [
    "hrm:question/established-scar-remodelling-to-native-architecture"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/henderson-2020-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/established-scar-repair"
    ],
    "blockedBy": [
     "hrm:question/established-scar-remodelling-to-native-architecture"
    ],
    "contradictedBy": [
     "hrm:claim/no-therapy-reverses-established-fibrosis"
    ]
   }
  },
  {
   "id": "hrm:capability/extracellular-matrix--edit",
   "type": "capability",
   "derived": true,
   "name": "Extracellular matrix: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Extracellular matrix (not a cell).",
   "target": {
    "node": "hrm:cell/extracellular-matrix"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L1",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Crosslink breakers have repeatedly failed. Elastin is not replaced after development."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/extracellular-matrix.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/extracellular-matrix--model",
   "type": "capability",
   "derived": true,
   "name": "Extracellular matrix: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Extracellular matrix (not a cell).",
   "target": {
    "node": "hrm:cell/extracellular-matrix"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "No specification exists for healthy matrix composition by tissue and age."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/extracellular-matrix.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/extracellular-matrix--reach",
   "type": "capability",
   "derived": true,
   "name": "Extracellular matrix: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Extracellular matrix (not a cell).",
   "target": {
    "node": "hrm:cell/extracellular-matrix"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Acellular and secreted — there is no cell to target for most of it."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/extracellular-matrix.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/extracellular-matrix--see",
   "type": "capability",
   "derived": true,
   "name": "Extracellular matrix: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Extracellular matrix (not a cell).",
   "target": {
    "node": "hrm:cell/extracellular-matrix"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Histology on biopsy; almost nothing in a living person."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/extracellular-matrix.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/extracellular-matrix--verify",
   "type": "capability",
   "derived": true,
   "name": "Extracellular matrix: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Extracellular matrix (not a cell).",
   "target": {
    "node": "hrm:cell/extracellular-matrix"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Barely measurable in vivo."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/extracellular-matrix.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/fetal-scarless-healing-target-state",
   "name": "Human skin that heals without scar exists (early-gestation fetus)",
   "class": "model",
   "primitive": "regenerate",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Know a human skin state in which full-thickness wounds heal by regeneration rather than scar, and what distinguishes it from adult skin.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "structure",
    "blocked": "science",
    "note": "Early-gestation fetal skin, human and animal, heals full-thickness wounds without scar; the transition to scarring healing occurs in late gestation, and the differences in inflammation, growth-factor profile and matrix are catalogued (Larson 2010, review). Review-level citation: primary human fetal-surgery series are not attached here. This is an observation about a state, not an intervention in adults."
   },
   "blockedBy": [
    "hrm:question/fetal-conditions-reproducible-in-adult-skin"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/larson-2010-prs"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-biological-control"
    ],
    "blockedBy": [
     "hrm:question/fetal-conditions-reproducible-in-adult-skin"
    ],
    "supportedBy": [
     "hrm:claim/fetal-skin-heals-without-scar"
    ]
   }
  },
  {
   "id": "hrm:capability/fibroblast--edit",
   "type": "capability",
   "derived": true,
   "name": "Fibroblast: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Fibroblast.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Two antifibrotics slow lung fibrosis. No therapy reverses established scar in any organ."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/fibroblast.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/fibroblast--model",
   "type": "capability",
   "derived": true,
   "name": "Fibroblast: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Fibroblast.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "The gap: nobody can specify a healthy fibroblast set-point, only pathological activation."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/fibroblast.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/fibroblast--reach",
   "type": "capability",
   "derived": true,
   "name": "Fibroblast: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Fibroblast.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Ubiquitous and non-specific, which makes selective targeting hard."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/fibroblast.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/fibroblast--see",
   "type": "capability",
   "derived": true,
   "name": "Fibroblast: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Fibroblast.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Activated states identifiable in biopsy; no in vivo readout."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/fibroblast.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/fibroblast--verify",
   "type": "capability",
   "derived": true,
   "name": "Fibroblast: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Fibroblast.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Fibrosis regression is barely measurable in vivo."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/fibroblast.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/fibroblast-state-sensing-in-living-wound",
   "name": "Measure fibroblast state in a living human wound",
   "class": "see",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Read, non-destructively and repeatedly, whether the fibroblasts in a human wound are on a fibrotic or regenerative trajectory, early enough to intervene.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "grade": {
    "basis": "ungraded",
    "note": "Lineage tracing answers this in mice by construction (Rinkevich 2015; Mascharak 2021); nothing equivalent exists for a living human wound short of biopsy. Not graded because the seed did not search intravital or liquid-biopsy approaches."
   },
   "blockedBy": [
    "hrm:question/nondestructive-fibroblast-state-readout-in-human-wounds"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-functional-restoration"
    ],
    "blockedBy": [
     "hrm:question/nondestructive-fibroblast-state-readout-in-human-wounds"
    ]
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/fibrogenic-fibroblast-lineage-control",
   "name": "Control the fibroblast lineage that produces scar",
   "class": "edit",
   "primitive": "recalibrate",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Identify the fibroblast population responsible for fibrotic deposition and prevent its activation or convert it, so that the regenerative population heals the wound.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "structure",
    "blocked": "science",
    "note": "Distinct dermal fibroblast lineages determine dermal architecture (Driskell 2013); the Engrailed-1 lineage carries intrinsic fibrogenic potential and produces the bulk of scar (Rinkevich 2015); tension drives Engrailed-1 activation and blocking it yields regeneration (Mascharak 2021). Three papers, two overlapping groups, all mouse. Human fibroblast heterogeneity is described but not controlled."
   },
   "blockedBy": [
    "hrm:question/en1-inhibition-translates-to-human-skin",
    "hrm:question/what-limits-regeneration-in-mus-and-human"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/driskell-2013-nature",
     "hrm:source/rinkevich-2015-science",
     "hrm:source/mascharak-2021-science"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-biological-control"
    ],
    "blockedBy": [
     "hrm:question/en1-inhibition-translates-to-human-skin",
     "hrm:question/what-limits-regeneration-in-mus-and-human"
    ],
    "supportedBy": [
     "hrm:claim/en1-lineage-fibroblasts-produce-scar",
     "hrm:claim/yap-inhibition-yields-mouse-wound-regeneration"
    ]
   }
  },
  {
   "id": "hrm:capability/germline--edit",
   "type": "capability",
   "derived": true,
   "name": "Germline (oocyte / spermatogonium): edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Germline (oocyte / spermatogonium).",
   "target": {
    "node": "hrm:cell/germline"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L1",
    "measured": "unspecified",
    "blocked": "framework",
    "note": "Technically demonstrated. Heritable human editing is prohibited nearly everywhere — the clearest framework-blocked row on this map."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/germline.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/germline--model",
   "type": "capability",
   "derived": true,
   "name": "Germline (oocyte / spermatogonium): model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Germline (oocyte / spermatogonium).",
   "target": {
    "node": "hrm:cell/germline"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Euploidy is a clear target; the oocyte ageing mechanism is not solved."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/germline.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/germline--reach",
   "type": "capability",
   "derived": true,
   "name": "Germline (oocyte / spermatogonium): reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Germline (oocyte / spermatogonium).",
   "target": {
    "node": "hrm:cell/germline"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Ex vivo access is routine in IVF."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/germline.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/germline--see",
   "type": "capability",
   "derived": true,
   "name": "Germline (oocyte / spermatogonium): see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Germline (oocyte / spermatogonium).",
   "target": {
    "node": "hrm:cell/germline"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Accessible and assessable through assisted reproduction."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/germline.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/germline--verify",
   "type": "capability",
   "derived": true,
   "name": "Germline (oocyte / spermatogonium): verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Germline (oocyte / spermatogonium).",
   "target": {
    "node": "hrm:cell/germline"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "framework",
    "note": "Verification would require following a person across a lifetime, which the prohibition forecloses."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/germline.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/glia--edit",
   "type": "capability",
   "derived": true,
   "name": "Glia (astrocyte, oligodendrocyte, microglia): edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Glia (astrocyte, oligodendrocyte, microglia).",
   "target": {
    "node": "hrm:cell/glia"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Remyelination remains unachieved in humans despite decades of trials."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/glia.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/glia--model",
   "type": "capability",
   "derived": true,
   "name": "Glia (astrocyte, oligodendrocyte, microglia): model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Glia (astrocyte, oligodendrocyte, microglia).",
   "target": {
    "node": "hrm:cell/glia"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Reactive gliosis is protective and obstructive at once. No agreed healthy target."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/glia.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/glia--reach",
   "type": "capability",
   "derived": true,
   "name": "Glia (astrocyte, oligodendrocyte, microglia): reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Glia (astrocyte, oligodendrocyte, microglia).",
   "target": {
    "node": "hrm:cell/glia"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Same barrier problem as neurons, with less cell-type specificity."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/glia.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/glia--see",
   "type": "capability",
   "derived": true,
   "name": "Glia (astrocyte, oligodendrocyte, microglia): see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Glia (astrocyte, oligodendrocyte, microglia).",
   "target": {
    "node": "hrm:cell/glia"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "PET ligands report microglial activation coarsely; astrocyte state is inaccessible."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/glia.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/glia--verify",
   "type": "capability",
   "derived": true,
   "name": "Glia (astrocyte, oligodendrocyte, microglia): verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Glia (astrocyte, oligodendrocyte, microglia).",
   "target": {
    "node": "hrm:cell/glia"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Imaging proxies only."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/glia.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/gut-epithelium--edit",
   "type": "capability",
   "derived": true,
   "name": "Intestinal epithelium: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Intestinal epithelium.",
   "target": {
    "node": "hrm:cell/gut-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "No approved cell-directed therapy; immunosuppression treats the driver instead."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/gut-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/gut-epithelium--model",
   "type": "capability",
   "derived": true,
   "name": "Intestinal epithelium: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Intestinal epithelium.",
   "target": {
    "node": "hrm:cell/gut-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Continuous renewal from a defined stem compartment."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/gut-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/gut-epithelium--reach",
   "type": "capability",
   "derived": true,
   "name": "Intestinal epithelium: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Intestinal epithelium.",
   "target": {
    "node": "hrm:cell/gut-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Oral delivery reaches the lumen; targeting epithelial cells specifically is unsolved."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/gut-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/gut-epithelium--see",
   "type": "capability",
   "derived": true,
   "name": "Intestinal epithelium: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Intestinal epithelium.",
   "target": {
    "node": "hrm:cell/gut-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Endoscopy and biopsy are routine and direct."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/gut-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/gut-epithelium--verify",
   "type": "capability",
   "derived": true,
   "name": "Intestinal epithelium: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Intestinal epithelium.",
   "target": {
    "node": "hrm:cell/gut-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Endoscopic healing is a validated endpoint."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/gut-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/hair-follicle-neogenesis-after-wounding",
   "name": "Regenerate new hair follicles in a healed wound",
   "class": "edit",
   "primitive": "regenerate",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "After a large full-thickness wound, new hair follicles form de novo in the healed skin, as in embryonic development.",
   "target": {
    "node": "hrm:cell/keratinocyte"
   },
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "structure",
    "blocked": "science",
    "note": "Wound-induced hair neogenesis occurs in adult mice after large excisional wounds and is Wnt-dependent (Ito 2007); the neogenic follicles then drive myofibroblast-to-adipocyte conversion (Plikus 2017). No report of de novo follicle neogenesis in adult human wounds located.",
    "drift": "'Mice regrow hair after wounding' is often generalised to humans; the human observation is absent."
   },
   "blockedBy": [
    "hrm:question/wound-induced-hair-neogenesis-in-human-skin"
   ],
   "wouldMove": "Documented follicle neogenesis (not follicle survival) in an adult human wound, by any group.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/ito-2007-nature",
     "hrm:source/plikus-2017-science"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/established-scar-repair",
     "hrm:goal/skin-structural-reconstruction"
    ],
    "blockedBy": [
     "hrm:question/wound-induced-hair-neogenesis-in-human-skin"
    ],
    "supportedBy": [
     "hrm:claim/myofibroblasts-regenerate-adipocytes-in-mouse-wounds",
     "hrm:claim/wound-induced-hair-neogenesis-in-adult-mice"
    ]
   }
  },
  {
   "id": "hrm:capability/hepatocyte--edit",
   "type": "capability",
   "derived": true,
   "name": "Hepatocyte: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Hepatocyte.",
   "target": {
    "node": "hrm:cell/hepatocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "In vivo CRISPR: NTLA-2001 for ATTR amyloidosis; base editing for PCSK9 in trials."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/hepatocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/hepatocyte--model",
   "type": "capability",
   "derived": true,
   "name": "Hepatocyte: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Hepatocyte.",
   "target": {
    "node": "hrm:cell/hepatocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Regeneration is well characterised; the healthy set-point for a diseased liver is less clear."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/hepatocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/hepatocyte--reach",
   "type": "capability",
   "derived": true,
   "name": "Hepatocyte: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Hepatocyte.",
   "target": {
    "node": "hrm:cell/hepatocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "The solved delivery problem. Lipid nanoparticles land in liver by default — patisiran approved 2018."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/hepatocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/hepatocyte--see",
   "type": "capability",
   "derived": true,
   "name": "Hepatocyte: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Hepatocyte.",
   "target": {
    "node": "hrm:cell/hepatocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Biopsy, elastography and serum enzymes are routine clinical practice."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/hepatocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/hepatocyte--verify",
   "type": "capability",
   "derived": true,
   "name": "Hepatocyte: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Hepatocyte.",
   "target": {
    "node": "hrm:cell/hepatocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Circulating protein levels give a direct, repeatable readout."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/hepatocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/hsc--edit",
   "type": "capability",
   "derived": true,
   "name": "Haematopoietic stem cell: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Haematopoietic stem cell.",
   "target": {
    "node": "hrm:cell/hsc"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Casgevy, ex vivo CRISPR for sickle cell disease, FDA 2023."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/hsc.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/hsc--model",
   "type": "capability",
   "derived": true,
   "name": "Haematopoietic stem cell: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Haematopoietic stem cell.",
   "target": {
    "node": "hrm:cell/hsc"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Lineage output is well defined and measurable."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/hsc.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/hsc--reach",
   "type": "capability",
   "derived": true,
   "name": "Haematopoietic stem cell: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Haematopoietic stem cell.",
   "target": {
    "node": "hrm:cell/hsc"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Ex vivo only: harvest, edit outside the body, reinfuse. In vivo HSC targeting is unsolved."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/hsc.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/hsc--see",
   "type": "capability",
   "derived": true,
   "name": "Haematopoietic stem cell: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Haematopoietic stem cell.",
   "target": {
    "node": "hrm:cell/hsc"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Marrow aspirate and flow cytometry are standard."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/hsc.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/hsc--verify",
   "type": "capability",
   "derived": true,
   "name": "Haematopoietic stem cell: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Haematopoietic stem cell.",
   "target": {
    "node": "hrm:cell/hsc"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Chimerism and haemoglobin fractions are directly measurable."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/hsc.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/immune-memory--edit",
   "type": "capability",
   "derived": true,
   "name": "Immune memory: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Immune memory (not a cell).",
   "target": {
    "node": "hrm:cell/immune-memory"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Allergen immunotherapy retrains it slowly. Autoimmune tolerance induction remains unreliable."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/immune-memory.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/immune-memory--model",
   "type": "capability",
   "derived": true,
   "name": "Immune memory: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Immune memory (not a cell).",
   "target": {
    "node": "hrm:cell/immune-memory"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "No specification of a healthy repertoire beyond statistical description."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/immune-memory.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/immune-memory--reach",
   "type": "capability",
   "derived": true,
   "name": "Immune memory: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Immune memory (not a cell).",
   "target": {
    "node": "hrm:cell/immune-memory"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Distributed across the body with no single location to target."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/immune-memory.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/immune-memory--see",
   "type": "capability",
   "derived": true,
   "name": "Immune memory: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Immune memory (not a cell).",
   "target": {
    "node": "hrm:cell/immune-memory"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Repertoire sequencing reads the whole memory from a blood draw — unusually good visibility."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/immune-memory.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/immune-memory--verify",
   "type": "capability",
   "derived": true,
   "name": "Immune memory: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Immune memory (not a cell).",
   "target": {
    "node": "hrm:cell/immune-memory"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Repertoire shifts measurable; clinical meaning uncertain."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/immune-memory.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/inflammation-phase-control-for-regeneration",
   "name": "Steer the inflammatory phase toward regeneration",
   "class": "edit",
   "primitive": "recalibrate",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Modulate the immune response to a wound so that it resolves into regeneration rather than fibrosis, as it does in regenerating mammals.",
   "target": {
    "node": "hrm:cell/immune-memory"
   },
   "grade": {
    "basis": "ungraded",
    "note": "A real node with no grade yet. Spiny-mouse and salamander work implicates the immune response, but the seed did not grade the intervention literature; the comparative question below is where the evidence should be attached first."
   },
   "blockedBy": [
    "hrm:question/what-limits-regeneration-in-mus-and-human"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-biological-control"
    ],
    "blockedBy": [
     "hrm:question/what-limits-regeneration-in-mus-and-human"
    ]
   }
  },
  {
   "id": "hrm:capability/keratinocyte--edit",
   "type": "capability",
   "derived": true,
   "name": "Keratinocyte: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Keratinocyte.",
   "target": {
    "node": "hrm:cell/keratinocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Vyjuvek, topical HSV-1 vector for dystrophic epidermolysis bullosa, FDA 2023."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/keratinocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/keratinocyte--model",
   "type": "capability",
   "derived": true,
   "name": "Keratinocyte: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Keratinocyte.",
   "target": {
    "node": "hrm:cell/keratinocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Healthy epidermis is unambiguous and continuously renewed."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/keratinocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/keratinocyte--reach",
   "type": "capability",
   "derived": true,
   "name": "Keratinocyte: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Keratinocyte.",
   "target": {
    "node": "hrm:cell/keratinocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Topical. Vyjuvek is a gel applied to the wound."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/keratinocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/keratinocyte--see",
   "type": "capability",
   "derived": true,
   "name": "Keratinocyte: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Keratinocyte.",
   "target": {
    "node": "hrm:cell/keratinocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Directly visible and biopsy is trivial."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/keratinocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/keratinocyte--verify",
   "type": "capability",
   "derived": true,
   "name": "Keratinocyte: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Keratinocyte.",
   "target": {
    "node": "hrm:cell/keratinocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Wound closure is observed by eye."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/keratinocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery",
   "name": "Deliver a therapeutic gene to keratinocytes in situ by topical application",
   "class": "reach",
   "primitive": "repair",
   "projections": [
    "universal-repair"
   ],
   "description": "Get a functional gene into the keratinocytes of a living wound by applying a vector to the skin surface, repeatedly, without surgery or cell culture.",
   "target": {
    "node": "hrm:cell/keratinocyte"
   },
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "function",
    "blocked": "none",
    "note": "Beremagene geperpavec (HSV-1 vector carrying COL7A1) closed 67% of treated versus 22% of placebo wounds at six months in a 31-patient intrapatient-randomised phase 3 (Guide 2022) and was approved by the FDA in May 2023. Single sponsor, one disease, one gene. Not blocked: the next rung is an independent trial, which nothing prevents.",
    "drift": "'Topical gene therapy' reads as general; it is one gene in one rare disease, and the vector does not persist, so dosing is weekly for life."
   },
   "blockedBy": [
    "hrm:question/topical-gene-delivery-generalises-beyond-eb"
   ],
   "wouldMove": "An unaffiliated group achieving durable expression with the same platform in a second indication or a second gene.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/guide-2022-nejm",
     "hrm:source/fda-2023-vyjuvek"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-structural-reconstruction"
    ],
    "blockedBy": [
     "hrm:question/topical-gene-delivery-generalises-beyond-eb"
    ],
    "supportedBy": [
     "hrm:claim/b-vec-topical-gene-therapy-closes-deb-wounds",
     "hrm:claim/fda-approved-b-vec-2023"
    ]
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/mammalian-scar-free-regeneration-target-state",
   "name": "An adult mammal that regenerates skin without scar (existence proof)",
   "class": "model",
   "primitive": "regenerate",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Know that scar-free regeneration of adult mammalian skin, with follicles, glands, dermis, nerves and vessels, is biologically possible — and have a living model in which to find out how.",
   "target": {
    "node": "hrm:cell/tissue-architecture"
   },
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "structure",
    "blocked": "science",
    "note": "African spiny mice (Acomys) regenerate full-thickness dorsal skin and 4 mm ear punches with hair follicles, sebaceous glands, dermis, cartilage, muscle and nerve, where C57BL/6 mice scar (Seifert 2012; Brant 2016; Maden 2018; Gawriluk 2016 — overlapping authorship — and Matias Santos 2016, an unaffiliated group). Acomys is a rodent, so this is L2 by the ladder's letter; it is an existence proof, not an intervention."
   },
   "blockedBy": [
    "hrm:question/what-limits-regeneration-in-mus-and-human"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/seifert-2012-nature",
     "hrm:source/brant-2016-wrr",
     "hrm:source/maden-2018-burns",
     "hrm:source/gawriluk-2016-natcommun",
     "hrm:source/matias-santos-2016-regeneration"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-biological-control"
    ],
    "blockedBy": [
     "hrm:question/what-limits-regeneration-in-mus-and-human"
    ],
    "supportedBy": [
     "hrm:claim/acomys-ear-regeneration-independent-replication",
     "hrm:claim/acomys-regenerates-full-thickness-skin-without-scar"
    ]
   }
  },
  {
   "id": "hrm:capability/melanocyte--edit",
   "type": "capability",
   "derived": true,
   "name": "Melanocyte: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Melanocyte.",
   "target": {
    "node": "hrm:cell/melanocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "JAK inhibitors modulate the autoimmune driver; melanocytes are not repaired or replaced."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/melanocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-structural-reconstruction"
    ]
   }
  },
  {
   "id": "hrm:capability/melanocyte--model",
   "type": "capability",
   "derived": true,
   "name": "Melanocyte: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Melanocyte.",
   "target": {
    "node": "hrm:cell/melanocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Repigmentation is an unambiguous target."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/melanocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/melanocyte--reach",
   "type": "capability",
   "derived": true,
   "name": "Melanocyte: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Melanocyte.",
   "target": {
    "node": "hrm:cell/melanocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Topical and intralesional access is straightforward."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/melanocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/melanocyte--see",
   "type": "capability",
   "derived": true,
   "name": "Melanocyte: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Melanocyte.",
   "target": {
    "node": "hrm:cell/melanocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Directly visible; dermoscopy and biopsy are routine."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/melanocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/melanocyte--verify",
   "type": "capability",
   "derived": true,
   "name": "Melanocyte: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Melanocyte.",
   "target": {
    "node": "hrm:cell/melanocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Repigmentation is visible and photographable."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/melanocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/microbiome--edit",
   "type": "capability",
   "derived": true,
   "name": "Microbiome: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Microbiome (not a cell).",
   "target": {
    "node": "hrm:cell/microbiome"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Faecal transplant products approved 2022–23 for recurrent C. difficile. Crude but effective."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/microbiome.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/microbiome--model",
   "type": "capability",
   "derived": true,
   "name": "Microbiome: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Microbiome (not a cell).",
   "target": {
    "node": "hrm:cell/microbiome"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Nobody can specify a healthy microbiome; it varies enormously between healthy people."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/microbiome.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/microbiome--reach",
   "type": "capability",
   "derived": true,
   "name": "Microbiome: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Microbiome (not a cell).",
   "target": {
    "node": "hrm:cell/microbiome"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Oral and rectal routes reach it directly."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/microbiome.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/microbiome--see",
   "type": "capability",
   "derived": true,
   "name": "Microbiome: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Microbiome (not a cell).",
   "target": {
    "node": "hrm:cell/microbiome"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Metagenomic sequencing of stool is cheap and comprehensive."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/microbiome.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/microbiome--verify",
   "type": "capability",
   "derived": true,
   "name": "Microbiome: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Microbiome (not a cell).",
   "target": {
    "node": "hrm:cell/microbiome"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Engraftment measurable by sequencing; clinical endpoints clear for C. diff."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/microbiome.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/mineralised-structure--edit",
   "type": "capability",
   "derived": true,
   "name": "Mineralised structure: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Mineralised structure (not a cell).",
   "target": {
    "node": "hrm:cell/mineralised-structure"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Bone remodels and can be pharmacologically shifted. Enamel is never regenerated once lost."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/mineralised-structure.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/mineralised-structure--model",
   "type": "capability",
   "derived": true,
   "name": "Mineralised structure: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Mineralised structure (not a cell).",
   "target": {
    "node": "hrm:cell/mineralised-structure"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Density and microarchitecture targets are established."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/mineralised-structure.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/mineralised-structure--reach",
   "type": "capability",
   "derived": true,
   "name": "Mineralised structure: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Mineralised structure (not a cell).",
   "target": {
    "node": "hrm:cell/mineralised-structure"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Bone-seeking agents localise well."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/mineralised-structure.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/mineralised-structure--see",
   "type": "capability",
   "derived": true,
   "name": "Mineralised structure: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Mineralised structure (not a cell).",
   "target": {
    "node": "hrm:cell/mineralised-structure"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "DEXA and CT quantify mineral directly."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/mineralised-structure.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/mineralised-structure--verify",
   "type": "capability",
   "derived": true,
   "name": "Mineralised structure: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Mineralised structure (not a cell).",
   "target": {
    "node": "hrm:cell/mineralised-structure"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "DEXA and fracture rates."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/mineralised-structure.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/native-ecm-organisation-reconstruction",
   "name": "Reconstruct native extracellular-matrix organisation",
   "class": "edit",
   "primitive": "regenerate",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Lay down dermal collagen and elastin in the basket-weave organisation of uninjured skin rather than the parallel bundles of scar.",
   "target": {
    "node": "hrm:cell/extracellular-matrix"
   },
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "structure",
    "blocked": "science",
    "note": "Mouse only: regeneration of dermal ultrastructure accompanied Engrailed-1 blockade (Mascharak 2021). No independent replication located; no human evidence."
   },
   "blockedBy": [
    "hrm:question/en1-inhibition-translates-to-human-skin"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/mascharak-2021-science"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/established-scar-repair",
     "hrm:goal/skin-structural-reconstruction"
    ],
    "blockedBy": [
     "hrm:question/en1-inhibition-translates-to-human-skin"
    ],
    "supportedBy": [
     "hrm:claim/yap-inhibition-yields-mouse-wound-regeneration"
    ]
   }
  },
  {
   "id": "hrm:capability/nephron-epithelium--edit",
   "type": "capability",
   "derived": true,
   "name": "Nephron epithelium: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Nephron epithelium.",
   "target": {
    "node": "hrm:cell/nephron-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L1",
    "measured": "unspecified",
    "blocked": "science",
    "note": "No approved therapy repairs or replaces nephron cells. Dialysis substitutes function."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/nephron-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/nephron-epithelium--model",
   "type": "capability",
   "derived": true,
   "name": "Nephron epithelium: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Nephron epithelium.",
   "target": {
    "node": "hrm:cell/nephron-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Nephron architecture is a 3-D pattern cells do not re-derive."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/nephron-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/nephron-epithelium--reach",
   "type": "capability",
   "derived": true,
   "name": "Nephron epithelium: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Nephron epithelium.",
   "target": {
    "node": "hrm:cell/nephron-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Filtration means most agents pass through rather than into tubular cells."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/nephron-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/nephron-epithelium--see",
   "type": "capability",
   "derived": true,
   "name": "Nephron epithelium: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Nephron epithelium.",
   "target": {
    "node": "hrm:cell/nephron-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "eGFR reports whole-organ function; biopsy is invasive and focal."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/nephron-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/nephron-epithelium--verify",
   "type": "capability",
   "derived": true,
   "name": "Nephron epithelium: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Nephron epithelium.",
   "target": {
    "node": "hrm:cell/nephron-epithelium"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "eGFR and proteinuria are reliable functional measures."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/nephron-epithelium.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/neural-connectivity--edit",
   "type": "capability",
   "derived": true,
   "name": "Neural connectivity: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Neural connectivity (not a cell).",
   "target": {
    "node": "hrm:cell/neural-connectivity"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L1",
    "measured": "unspecified",
    "blocked": "science",
    "note": "No human wiring has been deliberately restored. Rehabilitation exploits existing plasticity."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/neural-connectivity.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/neural-connectivity--model",
   "type": "capability",
   "derived": true,
   "name": "Neural connectivity: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Neural connectivity (not a cell).",
   "target": {
    "node": "hrm:cell/neural-connectivity"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L1",
    "measured": "unspecified",
    "blocked": "science",
    "note": "The hardest cell on this grid: a healthy connectome is the person, so the target state is the identity."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/neural-connectivity.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/neural-connectivity--reach",
   "type": "capability",
   "derived": true,
   "name": "Neural connectivity: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Neural connectivity (not a cell).",
   "target": {
    "node": "hrm:cell/neural-connectivity"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Deep brain stimulation modulates activity; it does not rewire."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/neural-connectivity.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/neural-connectivity--see",
   "type": "capability",
   "derived": true,
   "name": "Neural connectivity: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Neural connectivity (not a cell).",
   "target": {
    "node": "hrm:cell/neural-connectivity"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Full connectomes exist only post-mortem. Living imaging is orders of magnitude too coarse."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/neural-connectivity.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/neural-connectivity--verify",
   "type": "capability",
   "derived": true,
   "name": "Neural connectivity: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Neural connectivity (not a cell).",
   "target": {
    "node": "hrm:cell/neural-connectivity"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Behaviour is the only readout, and it is confounded."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/neural-connectivity.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/organised-microvascular-network-in-regenerated-dermis",
   "name": "Grow an organised, perfused microvascular network in thick regenerated tissue",
   "class": "edit",
   "primitive": "regenerate",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Induce a hierarchical, perfused capillary network throughout a regenerated or engineered dermis thicker than the diffusion limit, connected to the host circulation with normal geometry and long-term stability.",
   "target": {
    "node": "hrm:cell/endothelium"
   },
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "structure",
    "blocked": "science",
    "note": "Reviews of vascularisation in tissue engineering describe the problem as unsolved beyond roughly the diffusion distance: prevascularisation and angiogenic strategies yield networks in rodents but not organised, stable, clinically usable vasculature in thick constructs (Rouwkema 2016; Laschke 2016). Thin split-thickness grafts revascularise routinely by inosculation; that is a different, solved capability and is what makes skin grafting work at all.",
    "drift": "'Vascularised engineered tissue' usually means capillary sprouting in a small rodent construct."
   },
   "blockedBy": [
    "hrm:question/organised-microvasculature-in-thick-regenerated-tissue"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/rouwkema-2016-trendsbiotech",
     "hrm:source/laschke-2016-biotechadv"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/established-scar-repair",
     "hrm:goal/skin-structural-reconstruction"
    ],
    "blockedBy": [
     "hrm:question/organised-microvasculature-in-thick-regenerated-tissue"
    ],
    "contradictedBy": [
     "hrm:claim/thick-engineered-tissue-vascularisation-unsolved"
    ]
   }
  },
  {
   "id": "hrm:capability/peripheral-neuron--edit",
   "type": "capability",
   "derived": true,
   "name": "Peripheral neuron: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Peripheral neuron.",
   "target": {
    "node": "hrm:cell/peripheral-neuron"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Surgical repair and conduits assist regrowth; no cell-level therapy."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/peripheral-neuron.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/peripheral-neuron--model",
   "type": "capability",
   "derived": true,
   "name": "Peripheral neuron: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Peripheral neuron.",
   "target": {
    "node": "hrm:cell/peripheral-neuron"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Reinnervation of a known target is a clear goal."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/peripheral-neuron.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/peripheral-neuron--reach",
   "type": "capability",
   "derived": true,
   "name": "Peripheral neuron: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Peripheral neuron.",
   "target": {
    "node": "hrm:cell/peripheral-neuron"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Surgically accessible at specific sites; diffuse neuropathy is not addressable."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/peripheral-neuron.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/peripheral-neuron--see",
   "type": "capability",
   "derived": true,
   "name": "Peripheral neuron: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Peripheral neuron.",
   "target": {
    "node": "hrm:cell/peripheral-neuron"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Nerve conduction studies and EMG are routine."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/peripheral-neuron.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/peripheral-neuron--verify",
   "type": "capability",
   "derived": true,
   "name": "Peripheral neuron: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Peripheral neuron.",
   "target": {
    "node": "hrm:cell/peripheral-neuron"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Conduction and function are directly measurable."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/peripheral-neuron.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/pharmacological-scar-reduction-in-humans",
   "name": "Reduce scarring pharmacologically in human wounds",
   "class": "edit",
   "primitive": "recalibrate",
   "projections": [
    "universal-repair"
   ],
   "description": "Administer an agent around the time of wounding that measurably improves the appearance and structure of the resulting human scar.",
   "target": {
    "node": "hrm:cell/fibroblast"
   },
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "structure",
    "blocked": "science",
    "note": "Intradermal avotermin (recombinant TGF-β3) improved scar scores in three double-blind placebo-controlled phase I/II studies in healthy volunteers (Ferguson 2009) and in a phase II surgical trial (McCollum 2011), all sponsor-run (Renovo). The sponsor reported in 2011 that the phase 3 programme failed to meet its endpoints; no peer-reviewed publication of that phase 3 was located as of 2026-09-11. The rung records what was published, the drift records what happened next.",
    "drift": "The most-cited human anti-scarring result did not survive its phase 3, and the failure is barely visible in the literature because it was never published."
   },
   "blockedBy": [
    "hrm:question/why-avotermin-phase-3-failed"
   ],
   "wouldMove": "Any agent improving a validated scar score in a phase 3 by an unaffiliated group, with the trial published whatever its outcome.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/ferguson-2009-lancet",
     "hrm:source/mccollum-2011-bjs"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-biological-control"
    ],
    "blockedBy": [
     "hrm:question/why-avotermin-phase-3-failed"
    ],
    "supportedBy": [
     "hrm:claim/avotermin-improved-scar-appearance-phase-1-2",
     "hrm:claim/avotermin-phase-2-surgical-scar-improvement"
    ]
   }
  },
  {
   "id": "hrm:capability/photoreceptor-rpe--edit",
   "type": "capability",
   "derived": true,
   "name": "Photoreceptor / retinal pigment epithelium: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Photoreceptor / retinal pigment epithelium.",
   "target": {
    "node": "hrm:cell/photoreceptor-rpe"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Luxturna corrects RPE65 in one genotype; broader photoreceptor rescue remains unproven."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/photoreceptor-rpe.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/photoreceptor-rpe--model",
   "type": "capability",
   "derived": true,
   "name": "Photoreceptor / retinal pigment epithelium: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Photoreceptor / retinal pigment epithelium.",
   "target": {
    "node": "hrm:cell/photoreceptor-rpe"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Structure is well mapped; restoring degenerated architecture is not solved."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/photoreceptor-rpe.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/photoreceptor-rpe--reach",
   "type": "capability",
   "derived": true,
   "name": "Photoreceptor / retinal pigment epithelium: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Photoreceptor / retinal pigment epithelium.",
   "target": {
    "node": "hrm:cell/photoreceptor-rpe"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Subretinal injection into a small, immune-privileged, enclosed compartment."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/photoreceptor-rpe.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/photoreceptor-rpe--see",
   "type": "capability",
   "derived": true,
   "name": "Photoreceptor / retinal pigment epithelium: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Photoreceptor / retinal pigment epithelium.",
   "target": {
    "node": "hrm:cell/photoreceptor-rpe"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Adaptive-optics imaging resolves individual cones in a living eye."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/photoreceptor-rpe.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/photoreceptor-rpe--verify",
   "type": "capability",
   "derived": true,
   "name": "Photoreceptor / retinal pigment epithelium: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Photoreceptor / retinal pigment epithelium.",
   "target": {
    "node": "hrm:cell/photoreceptor-rpe"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Visual function and OCT structure both measurable."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/photoreceptor-rpe.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/regeneration-verification-histology-and-scar-scales",
   "name": "Verify a repair outcome by histology and validated scar scales",
   "class": "verify",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Confirm after repair whether native architecture was restored, using biopsy histology and validated observer or patient scar scales, and detect late failure.",
   "grade": {
    "basis": "standard-of-care",
    "rung": "L5",
    "measured": "structure",
    "blocked": "none",
    "note": "Biopsy histology and validated scar scales (POSAS, Vancouver) are the accepted endpoints of the trials cited on this map (Ferguson 2009; McCollum 2011). Verification is destructive or observational and does not confirm cell-level state."
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-functional-restoration"
    ]
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/rejuvenated-state-persistence",
   "name": "Make a rejuvenated state persist, or re-dose safely",
   "class": "verify",
   "primitive": "preserve",
   "projections": [
    "rejuvenation"
   ],
   "description": "After rejuvenation, the tissue stays young for a clinically meaningful time, or can be re-treated without cumulative harm — and the verification exists to know which.",
   "grade": {
    "basis": "ungraded",
    "note": "Not graded. Persistence beyond the treatment window has not been characterised in any human tissue; mouse durations are reported per study and were not collated here."
   },
   "blockedBy": [
    "hrm:question/rejuvenated-state-persistence-and-redosing"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/systemic-rejuvenation"
    ],
    "blockedBy": [
     "hrm:question/rejuvenated-state-persistence-and-redosing"
    ]
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
   "name": "Reset a tissue's epigenetic age in vivo without loss of function",
   "class": "edit",
   "primitive": "repair",
   "projections": [
    "rejuvenation"
   ],
   "description": "Express reprogramming factors transiently in a living tissue so that its DNA-methylation and transcriptional patterns return toward youthful ones and function improves, without dedifferentiation or tumours.",
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "function",
    "blocked": "science",
    "note": "OSK expression in mouse retinal ganglion cells restored youthful methylation and transcriptomes, promoted axon regeneration and reversed vision loss in glaucoma and aged mice (Lu 2020). Cyclic OSKM extended lifespan in progeroid mice and improved injury recovery in aged wild-type mice without teratomas (Ocampo 2016). Two groups, mouse. A sponsor dosed the first human with an OSK therapy in one eye in June 2026 (phase 1, safety primary); that is a running experiment, not evidence.",
    "drift": "Reported as 'age reversal in humans has begun'; what has begun is a phase 1 safety study of one eye."
   },
   "blockedBy": [
    "hrm:question/partial-reprogramming-human-safety"
   ],
   "wouldMove": "A human tissue showing a measurable functional gain with retained cell identity and no proliferative signal, then the same from an unaffiliated group.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/lu-2020-nature",
     "hrm:source/ocampo-2016-cell",
     "hrm:source/life-biosciences-2026-er100-first-dosed"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/systemic-rejuvenation"
    ],
    "blockedBy": [
     "hrm:question/partial-reprogramming-human-safety"
    ],
    "supportedBy": [
     "hrm:claim/cyclic-partial-reprogramming-ameliorates-aging-in-mice",
     "hrm:claim/osk-reprogramming-restores-vision-in-mice"
    ]
   }
  },
  {
   "id": "hrm:capability/skeletal-muscle--edit",
   "type": "capability",
   "derived": true,
   "name": "Skeletal muscle fibre / satellite cell: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Skeletal muscle fibre / satellite cell.",
   "target": {
    "node": "hrm:cell/skeletal-muscle"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Elevidys for Duchenne, FDA 2023 — accelerated, and the benefit remains debated."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/skeletal-muscle.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/skeletal-muscle--model",
   "type": "capability",
   "derived": true,
   "name": "Skeletal muscle fibre / satellite cell: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Skeletal muscle fibre / satellite cell.",
   "target": {
    "node": "hrm:cell/skeletal-muscle"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Healthy muscle is well characterised; the ageing set-point is contested."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/skeletal-muscle.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/skeletal-muscle--reach",
   "type": "capability",
   "derived": true,
   "name": "Skeletal muscle fibre / satellite cell: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Skeletal muscle fibre / satellite cell.",
   "target": {
    "node": "hrm:cell/skeletal-muscle"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Systemic AAV reaches muscle but total body mass makes dose the binding limit."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/skeletal-muscle.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/skeletal-muscle--see",
   "type": "capability",
   "derived": true,
   "name": "Skeletal muscle fibre / satellite cell: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Skeletal muscle fibre / satellite cell.",
   "target": {
    "node": "hrm:cell/skeletal-muscle"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Biopsy and MRI work; whole-body fibre-level state does not exist."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/skeletal-muscle.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/skeletal-muscle--verify",
   "type": "capability",
   "derived": true,
   "name": "Skeletal muscle fibre / satellite cell: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Skeletal muscle fibre / satellite cell.",
   "target": {
    "node": "hrm:cell/skeletal-muscle"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Function tests and dystrophin expression; long-term durability unproven."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/skeletal-muscle.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/skin-haemostasis",
   "name": "Stop bleeding from a skin injury",
   "class": "control",
   "primitive": "stop",
   "projections": [
    "universal-repair"
   ],
   "description": "Arrest haemorrhage from a cutaneous or subcutaneous wound within minutes so that perfusion and tissue are not lost before repair begins.",
   "target": {
    "node": "hrm:cell/endothelium"
   },
   "grade": {
    "basis": "standard-of-care",
    "rung": "L5",
    "measured": "function",
    "blocked": "none",
    "note": "Pressure, ligation, suture, electrocautery and topical haemostatic dressings are routine surgical practice worldwide; the demonstration predates the literature this map cites. Non-compressible internal haemorrhage is a different, unsolved capability and is not graded here."
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-immediate-stabilisation"
    ]
   }
  },
  {
   "id": "hrm:capability/smooth-muscle--edit",
   "type": "capability",
   "derived": true,
   "name": "Smooth muscle cell: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Smooth muscle cell.",
   "target": {
    "node": "hrm:cell/smooth-muscle"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "No cell-directed therapy; stents and drugs address consequences."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/smooth-muscle.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/smooth-muscle--model",
   "type": "capability",
   "derived": true,
   "name": "Smooth muscle cell: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Smooth muscle cell.",
   "target": {
    "node": "hrm:cell/smooth-muscle"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Contractile versus synthetic phenotype is a spectrum with no clear set-point."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/smooth-muscle.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/smooth-muscle--reach",
   "type": "capability",
   "derived": true,
   "name": "Smooth muscle cell: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Smooth muscle cell.",
   "target": {
    "node": "hrm:cell/smooth-muscle"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Reachable in vessel walls but not selectively."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/smooth-muscle.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/smooth-muscle--see",
   "type": "capability",
   "derived": true,
   "name": "Smooth muscle cell: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Smooth muscle cell.",
   "target": {
    "node": "hrm:cell/smooth-muscle"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Imaging shows vessel structure, not cell phenotype."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/smooth-muscle.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/smooth-muscle--verify",
   "type": "capability",
   "derived": true,
   "name": "Smooth muscle cell: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Smooth muscle cell.",
   "target": {
    "node": "hrm:cell/smooth-muscle"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Structural imaging only."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/smooth-muscle.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/synthetic-haemostat-for-noncompressible-haemorrhage",
   "name": "Induce haemostasis with a synthetic injectable agent",
   "class": "control",
   "primitive": "stop",
   "projections": [
    "universal-repair"
   ],
   "description": "Stop bleeding that cannot be compressed (internal, solid-organ) with an injectable synthetic agent rather than surgery or donor blood products.",
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "function",
    "blocked": "science",
    "note": "A synthetic fibrin-cross-linking polymer improved haemostasis in rodent trauma models (Chan 2015). No human data cited here; large-animal translation and immunogenicity unknown.",
    "drift": "Often described as 'a synthetic blood-clotting drug'; the evidence is rodent survival and blood-loss endpoints."
   },
   "wouldMove": "A large-animal (porcine) non-compressible haemorrhage study by an independent group, then a first-in-human safety study.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/chan-2015-scitranslmed"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "supportedBy": [
     "hrm:claim/synthetic-fibrin-crosslinker-induces-haemostasis-in-rodents"
    ]
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/systemic-cell-type-specific-delivery",
   "name": "Deliver a payload to a chosen cell type throughout the body",
   "class": "reach",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "description": "Address a payload to one cell type across all its tissues from a systemic dose, at useful efficiency, repeatably, without off-target harm — the 'universal addressability' the black box needs.",
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "transduction",
    "blocked": "science",
    "note": "The best systemic case on this map is intravenous AAV9 in spinal muscular atrophy: clinical benefit is real and replicated, but direct evidence of human CNS transduction rests on two autopsies with liver vector hundreds-fold higher than CNS (Thomsen 2021). Liver and blood are tractable; arbitrary cell-type-specific delivery is not. The 16 graded CNS routes in this map are the detailed picture for one organ.",
    "drift": "'Systemic gene therapy reaches the brain' rests on n=2 post-mortem samples."
   },
   "blockedBy": [
    "hrm:question/rejuvenation-reach-beyond-eye-and-liver"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/thomsen-2021-natmed"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/systemic-rejuvenation"
    ],
    "blockedBy": [
     "hrm:question/rejuvenation-reach-beyond-eye-and-liver"
    ],
    "supportedBy": [
     "hrm:claim/iv-aav9-human-cns-transduction-rests-on-two-autopsies"
    ]
   }
  },
  {
   "id": "hrm:capability/t-lymphocyte--edit",
   "type": "capability",
   "derived": true,
   "name": "T lymphocyte: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: T lymphocyte.",
   "target": {
    "node": "hrm:cell/t-lymphocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Six approved CAR-T products since 2017."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/t-lymphocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/t-lymphocyte--model",
   "type": "capability",
   "derived": true,
   "name": "T lymphocyte: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: T lymphocyte.",
   "target": {
    "node": "hrm:cell/t-lymphocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "A healthy repertoire is describable statistically, not specified precisely."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/t-lymphocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/t-lymphocyte--reach",
   "type": "capability",
   "derived": true,
   "name": "T lymphocyte: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: T lymphocyte.",
   "target": {
    "node": "hrm:cell/t-lymphocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Ex vivo engineering is routine; in vivo CAR generation is early-stage."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/t-lymphocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/t-lymphocyte--see",
   "type": "capability",
   "derived": true,
   "name": "T lymphocyte: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: T lymphocyte.",
   "target": {
    "node": "hrm:cell/t-lymphocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Flow cytometry and repertoire sequencing from a blood draw."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/t-lymphocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/t-lymphocyte--verify",
   "type": "capability",
   "derived": true,
   "name": "T lymphocyte: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: T lymphocyte.",
   "target": {
    "node": "hrm:cell/t-lymphocyte"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L5",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Persistence and expansion tracked directly in blood."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/t-lymphocyte.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/temporary-barrier-restoration",
   "name": "Restore a temporary barrier over a wound",
   "class": "control",
   "primitive": "replace",
   "projections": [
    "universal-repair"
   ],
   "description": "Cover an open wound with a dressing, allograft or temporary substitute that limits fluid loss and contamination until definitive repair.",
   "target": {
    "node": "hrm:cell/keratinocyte"
   },
   "grade": {
    "basis": "standard-of-care",
    "rung": "L5",
    "measured": "function",
    "blocked": "none",
    "note": "Occlusive dressings, cadaveric allograft and synthetic temporary substitutes are routine burn and wound care. Temporary is the operative word: none of these regenerates the skin beneath them."
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-immediate-stabilisation"
    ]
   }
  },
  {
   "id": "hrm:capability/tissue-architecture--edit",
   "type": "capability",
   "derived": true,
   "name": "Tissue architecture: edit",
   "class": "edit",
   "description": "Can we repair, replace, reprogram, regenerate or clear it? Target: Tissue architecture (not a cell).",
   "target": {
    "node": "hrm:cell/tissue-architecture"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L1",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Organoids self-organise in vitro at millimetre scale. Nothing rebuilds architecture in a human."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/tissue-architecture.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/tissue-architecture--model",
   "type": "capability",
   "derived": true,
   "name": "Tissue architecture: model",
   "class": "model",
   "description": "Do we know what a healthy target state for it is, and can we predict the effect of an intervention? Target: Tissue architecture (not a cell).",
   "target": {
    "node": "hrm:cell/tissue-architecture"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L2",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Positional information is the thing an axolotl has and we lack."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/tissue-architecture.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/tissue-architecture--reach",
   "type": "capability",
   "derived": true,
   "name": "Tissue architecture: reach",
   "class": "reach",
   "description": "Can we deliver something to it, specifically and repeatedly? Target: Tissue architecture (not a cell).",
   "target": {
    "node": "hrm:cell/tissue-architecture"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L1",
    "measured": "unspecified",
    "blocked": "science",
    "note": "You cannot deliver to a pattern."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/tissue-architecture.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/tissue-architecture--see",
   "type": "capability",
   "derived": true,
   "name": "Tissue architecture: see",
   "class": "see",
   "description": "Can we measure the state of this target in a living person? Target: Tissue architecture (not a cell).",
   "target": {
    "node": "hrm:cell/tissue-architecture"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L4",
    "measured": "unspecified",
    "blocked": "none",
    "note": "Imaging shows architecture well — this is what CT and MRI are for."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/tissue-architecture.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:capability/tissue-architecture--verify",
   "type": "capability",
   "derived": true,
   "name": "Tissue architecture: verify",
   "class": "verify",
   "description": "Can we confirm afterwards that it worked, and stayed working? Target: Tissue architecture (not a cell).",
   "target": {
    "node": "hrm:cell/tissue-architecture"
   },
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "grade": {
    "basis": "claims",
    "rung": "L3",
    "measured": "unspecified",
    "blocked": "science",
    "note": "Imaging can confirm structure if it were ever restored."
   },
   "provenance": {
    "proposedBy": {
     "type": "import",
     "name": "scripts/build.mjs"
    },
    "method": "derived from records/cells/tissue-architecture.json (v0.2 grid, graded 2026-07-28); the anchors on the cell record are the evidence",
    "date": "2026-07-28"
   },
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "type": "capability",
   "id": "hrm:capability/wound-bed-assessment-in-vivo",
   "name": "Assess wound depth, perfusion and infection in a living patient",
   "class": "see",
   "projections": [
    "universal-repair"
   ],
   "description": "Determine, non-destructively, how deep a wound is, whether its bed is perfused, and whether it is infected, well enough to choose a repair strategy.",
   "grade": {
    "basis": "standard-of-care",
    "rung": "L5",
    "measured": "function",
    "blocked": "none",
    "note": "Clinical examination, laser Doppler and indocyanine-green perfusion imaging, and microbiological sampling are routine in burn and wound units. Resolution stops at tissue: the state of individual cells is not observed."
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/skin-functional-restoration"
    ]
   }
  },
  {
   "id": "hrm:cell/adipocyte",
   "type": "cell",
   "name": "Adipocyte",
   "system": "Endocrine & metabolic",
   "kind": "cell",
   "renewal": "limited",
   "failures": "Hypertrophic dysfunction, ectopic deposition, lipodystrophy, inflammatory secretion.",
   "anchors": [
    "GLP-1 agonists act systemically, not on the adipocyte directly"
   ],
   "order": 5,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/adipocyte--see",
    "hrm:capability/adipocyte--model",
    "hrm:capability/adipocyte--reach",
    "hrm:capability/adipocyte--edit",
    "hrm:capability/adipocyte--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/dermal-adipocyte-regeneration",
     "hrm:capability/adipocyte--see",
     "hrm:capability/adipocyte--model",
     "hrm:capability/adipocyte--reach",
     "hrm:capability/adipocyte--edit",
     "hrm:capability/adipocyte--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/alveolar-epithelium",
   "type": "cell",
   "name": "Alveolar epithelium",
   "system": "Organ epithelia",
   "kind": "cell",
   "renewal": "limited",
   "failures": "Fibrosis, emphysematous destruction, cystic fibrosis channel defects, acute injury.",
   "anchors": [
    "Inhaled CF gene-editing programmes, early Phase"
   ],
   "order": 4,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/alveolar-epithelium--see",
    "hrm:capability/alveolar-epithelium--model",
    "hrm:capability/alveolar-epithelium--reach",
    "hrm:capability/alveolar-epithelium--edit",
    "hrm:capability/alveolar-epithelium--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/alveolar-epithelium--see",
     "hrm:capability/alveolar-epithelium--model",
     "hrm:capability/alveolar-epithelium--reach",
     "hrm:capability/alveolar-epithelium--edit",
     "hrm:capability/alveolar-epithelium--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/beta-cell",
   "type": "cell",
   "name": "Pancreatic islet β-cell",
   "system": "Endocrine & metabolic",
   "kind": "cell",
   "renewal": "minimal",
   "failures": "Autoimmune destruction in type 1, exhaustion in type 2. Silent until most mass is already gone.",
   "anchors": [
    "VX-880 stem-cell-derived islets, Phase 1/2",
    "Autoimmunity persists as the chronic driver"
   ],
   "order": 5,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/beta-cell--see",
    "hrm:capability/beta-cell--model",
    "hrm:capability/beta-cell--reach",
    "hrm:capability/beta-cell--edit",
    "hrm:capability/beta-cell--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/beta-cell--see",
     "hrm:capability/beta-cell--model",
     "hrm:capability/beta-cell--reach",
     "hrm:capability/beta-cell--edit",
     "hrm:capability/beta-cell--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/bone-cell",
   "type": "cell",
   "name": "Osteoblast / osteoclast",
   "system": "Musculoskeletal",
   "kind": "cell",
   "renewal": "self-renewing",
   "failures": "Osteoporotic imbalance, non-union fracture, osteogenesis imperfecta.",
   "anchors": [
    "Denosumab, FDA 2010",
    "Bone is one of few tissues that truly self-repairs"
   ],
   "order": 6,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/bone-cell--see",
    "hrm:capability/bone-cell--model",
    "hrm:capability/bone-cell--reach",
    "hrm:capability/bone-cell--edit",
    "hrm:capability/bone-cell--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/bone-cell--see",
     "hrm:capability/bone-cell--model",
     "hrm:capability/bone-cell--reach",
     "hrm:capability/bone-cell--edit",
     "hrm:capability/bone-cell--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/cardiomyocyte",
   "type": "cell",
   "name": "Cardiomyocyte",
   "system": "Cardiovascular",
   "kind": "cell",
   "renewal": "post-mitotic",
   "failures": "Ischaemic death replaced by scar, hypertrophy, inherited cardiomyopathy. Essentially no human renewal.",
   "anchors": [
    "RP-A501 for Danon disease, Phase 1",
    "Zebrafish cardiac regeneration literature"
   ],
   "order": 3,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/cardiomyocyte--see",
    "hrm:capability/cardiomyocyte--model",
    "hrm:capability/cardiomyocyte--reach",
    "hrm:capability/cardiomyocyte--edit",
    "hrm:capability/cardiomyocyte--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/cardiomyocyte--see",
     "hrm:capability/cardiomyocyte--model",
     "hrm:capability/cardiomyocyte--reach",
     "hrm:capability/cardiomyocyte--edit",
     "hrm:capability/cardiomyocyte--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/chondrocyte",
   "type": "cell",
   "name": "Chondrocyte (articular cartilage)",
   "system": "Musculoskeletal",
   "kind": "cell",
   "renewal": "none",
   "failures": "Focal defects and diffuse osteoarthritic loss. Avascular, so no repair signal reaches it.",
   "anchors": [
    "MACI, FDA 2016",
    "Avascularity is the mechanistic blocker"
   ],
   "order": 6,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/chondrocyte--see",
    "hrm:capability/chondrocyte--model",
    "hrm:capability/chondrocyte--reach",
    "hrm:capability/chondrocyte--edit",
    "hrm:capability/chondrocyte--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/chondrocyte--see",
     "hrm:capability/chondrocyte--model",
     "hrm:capability/chondrocyte--reach",
     "hrm:capability/chondrocyte--edit",
     "hrm:capability/chondrocyte--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/cns-neuron",
   "type": "cell",
   "name": "Central neuron",
   "system": "Nervous system",
   "kind": "cell",
   "renewal": "post-mitotic",
   "failures": "Neurodegeneration, stroke infarction, trauma. Glial scar blocks regrowth; no meaningful replacement.",
   "anchors": [
    "Nusinersen (Spinraza), FDA 2016",
    "CNS delivery module, this map"
   ],
   "order": 1,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/cns-neuron--see",
    "hrm:capability/cns-neuron--model",
    "hrm:capability/cns-neuron--reach",
    "hrm:capability/cns-neuron--edit",
    "hrm:capability/cns-neuron--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/cns-neuron--see",
     "hrm:capability/cns-neuron--model",
     "hrm:capability/cns-neuron--reach",
     "hrm:capability/cns-neuron--edit",
     "hrm:capability/cns-neuron--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/cochlear-hair-cell",
   "type": "cell",
   "name": "Cochlear hair cell",
   "system": "Sensory",
   "kind": "cell",
   "renewal": "post-mitotic",
   "failures": "Noise, ototoxic and age-related loss. Birds regenerate these; mammals do not.",
   "anchors": [
    "OTOF gene therapy trials, 2024",
    "Avian hair-cell regeneration literature"
   ],
   "order": 2,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/cochlear-hair-cell--see",
    "hrm:capability/cochlear-hair-cell--model",
    "hrm:capability/cochlear-hair-cell--reach",
    "hrm:capability/cochlear-hair-cell--edit",
    "hrm:capability/cochlear-hair-cell--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/cochlear-hair-cell--see",
     "hrm:capability/cochlear-hair-cell--model",
     "hrm:capability/cochlear-hair-cell--reach",
     "hrm:capability/cochlear-hair-cell--edit",
     "hrm:capability/cochlear-hair-cell--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/corneal-epithelium",
   "type": "cell",
   "name": "Corneal epithelium / limbal stem cell",
   "system": "Sensory",
   "kind": "cell",
   "renewal": "self-renewing",
   "failures": "Limbal stem cell deficiency after chemical burns, scarring, dystrophies.",
   "anchors": [
    "Holoclar, EMA 2015"
   ],
   "order": 2,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/corneal-epithelium--see",
    "hrm:capability/corneal-epithelium--model",
    "hrm:capability/corneal-epithelium--reach",
    "hrm:capability/corneal-epithelium--edit",
    "hrm:capability/corneal-epithelium--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/corneal-epithelium--see",
     "hrm:capability/corneal-epithelium--model",
     "hrm:capability/corneal-epithelium--reach",
     "hrm:capability/corneal-epithelium--edit",
     "hrm:capability/corneal-epithelium--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/endocrine-cell",
   "type": "cell",
   "name": "Thyroid / adrenal endocrine cell",
   "system": "Endocrine & metabolic",
   "kind": "cell",
   "renewal": "minimal",
   "failures": "Autoimmune destruction, nodular disease, adrenal insufficiency.",
   "anchors": [
    "Levothyroxine substitutes function without touching the gland"
   ],
   "order": 5,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/endocrine-cell--see",
    "hrm:capability/endocrine-cell--model",
    "hrm:capability/endocrine-cell--reach",
    "hrm:capability/endocrine-cell--edit",
    "hrm:capability/endocrine-cell--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/endocrine-cell--see",
     "hrm:capability/endocrine-cell--model",
     "hrm:capability/endocrine-cell--reach",
     "hrm:capability/endocrine-cell--edit",
     "hrm:capability/endocrine-cell--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/endothelium",
   "type": "cell",
   "name": "Vascular endothelium",
   "system": "Cardiovascular",
   "kind": "cell",
   "renewal": "limited",
   "failures": "Dysfunction preceding atherosclerosis, barrier breakdown, capillary rarefaction with age.",
   "anchors": [
    "Endothelial dysfunction precedes visible atherosclerosis by decades"
   ],
   "order": 3,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/endothelium--see",
    "hrm:capability/endothelium--model",
    "hrm:capability/endothelium--reach",
    "hrm:capability/endothelium--edit",
    "hrm:capability/endothelium--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/organised-microvascular-network-in-regenerated-dermis",
     "hrm:capability/skin-haemostasis",
     "hrm:capability/endothelium--see",
     "hrm:capability/endothelium--model",
     "hrm:capability/endothelium--reach",
     "hrm:capability/endothelium--edit",
     "hrm:capability/endothelium--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/extracellular-matrix",
   "type": "cell",
   "name": "Extracellular matrix",
   "system": "Structural & connective",
   "kind": "non-cell",
   "renewal": "slow turnover",
   "failures": "Collagen crosslinking with age, basement membrane failure, scar deposition, elastin loss that never regenerates.",
   "anchors": [
    "Elastin synthesis largely ceases after adolescence"
   ],
   "order": 8,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/extracellular-matrix--see",
    "hrm:capability/extracellular-matrix--model",
    "hrm:capability/extracellular-matrix--reach",
    "hrm:capability/extracellular-matrix--edit",
    "hrm:capability/extracellular-matrix--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/established-dermal-scar-reversal",
     "hrm:capability/native-ecm-organisation-reconstruction",
     "hrm:capability/extracellular-matrix--see",
     "hrm:capability/extracellular-matrix--model",
     "hrm:capability/extracellular-matrix--reach",
     "hrm:capability/extracellular-matrix--edit",
     "hrm:capability/extracellular-matrix--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/fibroblast",
   "type": "cell",
   "name": "Fibroblast",
   "system": "Structural & connective",
   "kind": "cell",
   "renewal": "self-renewing",
   "failures": "Fibrosis — the scar response that outcompetes regeneration across heart, lung, liver, kidney and CNS.",
   "anchors": [
    "Nintedanib and pirfenidone slow, never reverse, pulmonary fibrosis"
   ],
   "order": 8,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/fibroblast--see",
    "hrm:capability/fibroblast--model",
    "hrm:capability/fibroblast--reach",
    "hrm:capability/fibroblast--edit",
    "hrm:capability/fibroblast--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/dermal-architecture-regeneration-without-scar",
     "hrm:capability/dermal-substitute-for-chronic-wound-closure",
     "hrm:capability/fetal-scarless-healing-target-state",
     "hrm:capability/fibroblast-state-sensing-in-living-wound",
     "hrm:capability/fibrogenic-fibroblast-lineage-control",
     "hrm:capability/pharmacological-scar-reduction-in-humans",
     "hrm:capability/fibroblast--see",
     "hrm:capability/fibroblast--model",
     "hrm:capability/fibroblast--reach",
     "hrm:capability/fibroblast--edit",
     "hrm:capability/fibroblast--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/germline",
   "type": "cell",
   "name": "Germline (oocyte / spermatogonium)",
   "system": "Reproductive",
   "kind": "cell",
   "renewal": "sperm only",
   "failures": "Age-related oocyte aneuploidy, heritable mutation, infertility.",
   "anchors": [
    "Heritable genome editing prohibited across most jurisdictions since 2015 consensus"
   ],
   "order": 9,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/germline--see",
    "hrm:capability/germline--model",
    "hrm:capability/germline--reach",
    "hrm:capability/germline--edit",
    "hrm:capability/germline--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/germline--see",
     "hrm:capability/germline--model",
     "hrm:capability/germline--reach",
     "hrm:capability/germline--edit",
     "hrm:capability/germline--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/glia",
   "type": "cell",
   "name": "Glia (astrocyte, oligodendrocyte, microglia)",
   "system": "Nervous system",
   "kind": "cell",
   "renewal": "limited",
   "failures": "Reactive gliosis forming the scar that blocks CNS repair, demyelination, chronic neuroinflammation.",
   "anchors": [
    "Zebrafish Müller glia regenerate retina; human glia do not"
   ],
   "order": 1,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/glia--see",
    "hrm:capability/glia--model",
    "hrm:capability/glia--reach",
    "hrm:capability/glia--edit",
    "hrm:capability/glia--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/glia--see",
     "hrm:capability/glia--model",
     "hrm:capability/glia--reach",
     "hrm:capability/glia--edit",
     "hrm:capability/glia--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/gut-epithelium",
   "type": "cell",
   "name": "Intestinal epithelium",
   "system": "Organ epithelia",
   "kind": "cell",
   "renewal": "self-renewing",
   "failures": "Barrier failure, inflammatory destruction, malignant transformation. Renews every few days.",
   "anchors": [
    "Crypt stem cell renewal is among the fastest in the body"
   ],
   "order": 4,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/gut-epithelium--see",
    "hrm:capability/gut-epithelium--model",
    "hrm:capability/gut-epithelium--reach",
    "hrm:capability/gut-epithelium--edit",
    "hrm:capability/gut-epithelium--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/gut-epithelium--see",
     "hrm:capability/gut-epithelium--model",
     "hrm:capability/gut-epithelium--reach",
     "hrm:capability/gut-epithelium--edit",
     "hrm:capability/gut-epithelium--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/hepatocyte",
   "type": "cell",
   "name": "Hepatocyte",
   "system": "Organ epithelia",
   "kind": "cell",
   "renewal": "regenerative",
   "failures": "Steatosis, fibrosis to cirrhosis, metabolic enzyme deficiency, drug injury. The liver regrows mass readily but scars irreversibly.",
   "anchors": [
    "Patisiran (Onpattro), FDA 2018",
    "NTLA-2001 in vivo CRISPR, NEJM 2021"
   ],
   "order": 4,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/hepatocyte--see",
    "hrm:capability/hepatocyte--model",
    "hrm:capability/hepatocyte--reach",
    "hrm:capability/hepatocyte--edit",
    "hrm:capability/hepatocyte--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/hepatocyte--see",
     "hrm:capability/hepatocyte--model",
     "hrm:capability/hepatocyte--reach",
     "hrm:capability/hepatocyte--edit",
     "hrm:capability/hepatocyte--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/hsc",
   "type": "cell",
   "name": "Haematopoietic stem cell",
   "system": "Blood & immune",
   "kind": "cell",
   "renewal": "self-renewing",
   "failures": "Inherited haemoglobin and immune defects, clonal expansion to leukaemia, age-related clonal haematopoiesis.",
   "anchors": [
    "Casgevy (exagamglogene autotemcel), FDA 2023",
    "Lyfgenia, FDA 2023"
   ],
   "order": 0,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/hsc--see",
    "hrm:capability/hsc--model",
    "hrm:capability/hsc--reach",
    "hrm:capability/hsc--edit",
    "hrm:capability/hsc--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/hsc--see",
     "hrm:capability/hsc--model",
     "hrm:capability/hsc--reach",
     "hrm:capability/hsc--edit",
     "hrm:capability/hsc--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/immune-memory",
   "type": "cell",
   "name": "Immune memory",
   "system": "Blood & immune",
   "kind": "non-cell",
   "renewal": "dynamic",
   "failures": "Autoimmune memory that will not forget, allergic sensitisation, immunosenescence, vaccine non-response with age.",
   "anchors": [
    "Oral immunotherapy for peanut allergy, FDA 2020 — partial, slow, reversible"
   ],
   "order": 0,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/immune-memory--see",
    "hrm:capability/immune-memory--model",
    "hrm:capability/immune-memory--reach",
    "hrm:capability/immune-memory--edit",
    "hrm:capability/immune-memory--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/inflammation-phase-control-for-regeneration",
     "hrm:capability/immune-memory--see",
     "hrm:capability/immune-memory--model",
     "hrm:capability/immune-memory--reach",
     "hrm:capability/immune-memory--edit",
     "hrm:capability/immune-memory--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/keratinocyte",
   "type": "cell",
   "name": "Keratinocyte",
   "system": "Skin",
   "kind": "cell",
   "renewal": "self-renewing",
   "failures": "Blistering from structural gene defects, impaired wound healing, malignant transformation.",
   "anchors": [
    "Vyjuvek (beremagene geperpavec), FDA 2023"
   ],
   "order": 7,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/keratinocyte--see",
    "hrm:capability/keratinocyte--model",
    "hrm:capability/keratinocyte--reach",
    "hrm:capability/keratinocyte--edit",
    "hrm:capability/keratinocyte--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/epidermis-gene-corrected-stem-cell-replacement",
     "hrm:capability/epidermis-replacement-cultured-autograft",
     "hrm:capability/hair-follicle-neogenesis-after-wounding",
     "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery",
     "hrm:capability/temporary-barrier-restoration",
     "hrm:capability/keratinocyte--see",
     "hrm:capability/keratinocyte--model",
     "hrm:capability/keratinocyte--reach",
     "hrm:capability/keratinocyte--edit",
     "hrm:capability/keratinocyte--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/melanocyte",
   "type": "cell",
   "name": "Melanocyte",
   "system": "Skin",
   "kind": "cell",
   "renewal": "limited",
   "failures": "Autoimmune loss in vitiligo, malignant transformation to melanoma.",
   "anchors": [
    "Ruxolitinib cream for vitiligo, FDA 2022 — treats the driver, not the cell"
   ],
   "order": 7,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/melanocyte--see",
    "hrm:capability/melanocyte--model",
    "hrm:capability/melanocyte--reach",
    "hrm:capability/melanocyte--edit",
    "hrm:capability/melanocyte--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/melanocyte--see",
     "hrm:capability/melanocyte--model",
     "hrm:capability/melanocyte--reach",
     "hrm:capability/melanocyte--edit",
     "hrm:capability/melanocyte--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/microbiome",
   "type": "cell",
   "name": "Microbiome",
   "system": "Cross-cutting",
   "kind": "non-cell",
   "renewal": "self-renewing",
   "failures": "Dysbiosis after antibiotics, loss of diversity, C. difficile overgrowth. Not human cells at all.",
   "anchors": [
    "Rebyota, FDA 2022",
    "Vowst, FDA 2023"
   ],
   "order": 10,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/microbiome--see",
    "hrm:capability/microbiome--model",
    "hrm:capability/microbiome--reach",
    "hrm:capability/microbiome--edit",
    "hrm:capability/microbiome--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/acute-wound-infection-control",
     "hrm:capability/chronic-wound-biofilm-eradication",
     "hrm:capability/microbiome--see",
     "hrm:capability/microbiome--model",
     "hrm:capability/microbiome--reach",
     "hrm:capability/microbiome--edit",
     "hrm:capability/microbiome--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/mineralised-structure",
   "type": "cell",
   "name": "Mineralised structure",
   "system": "Musculoskeletal",
   "kind": "non-cell",
   "renewal": "bone only",
   "failures": "Osteoporotic loss, enamel erosion that never regenerates, non-union fractures.",
   "anchors": [
    "Enamel is acellular and has no regenerative capacity in humans"
   ],
   "order": 6,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/mineralised-structure--see",
    "hrm:capability/mineralised-structure--model",
    "hrm:capability/mineralised-structure--reach",
    "hrm:capability/mineralised-structure--edit",
    "hrm:capability/mineralised-structure--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/mineralised-structure--see",
     "hrm:capability/mineralised-structure--model",
     "hrm:capability/mineralised-structure--reach",
     "hrm:capability/mineralised-structure--edit",
     "hrm:capability/mineralised-structure--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/nephron-epithelium",
   "type": "cell",
   "name": "Nephron epithelium",
   "system": "Organ epithelia",
   "kind": "cell",
   "renewal": "minimal",
   "failures": "Progressive fibrosis, tubular injury, glomerular loss. Nephrons are never rebuilt after birth.",
   "anchors": [
    "Nephron endowment is fixed at birth in humans"
   ],
   "order": 4,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/nephron-epithelium--see",
    "hrm:capability/nephron-epithelium--model",
    "hrm:capability/nephron-epithelium--reach",
    "hrm:capability/nephron-epithelium--edit",
    "hrm:capability/nephron-epithelium--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/nephron-epithelium--see",
     "hrm:capability/nephron-epithelium--model",
     "hrm:capability/nephron-epithelium--reach",
     "hrm:capability/nephron-epithelium--edit",
     "hrm:capability/nephron-epithelium--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/neural-connectivity",
   "type": "cell",
   "name": "Neural connectivity",
   "system": "Nervous system",
   "kind": "non-cell",
   "renewal": "plasticity only",
   "failures": "Disconnection from stroke and trauma, synaptic loss in dementia, maladaptive rewiring in chronic pain.",
   "anchors": [
    "Deep brain stimulation modulates circuits without rewiring them"
   ],
   "order": 1,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/neural-connectivity--see",
    "hrm:capability/neural-connectivity--model",
    "hrm:capability/neural-connectivity--reach",
    "hrm:capability/neural-connectivity--edit",
    "hrm:capability/neural-connectivity--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/neural-connectivity--see",
     "hrm:capability/neural-connectivity--model",
     "hrm:capability/neural-connectivity--reach",
     "hrm:capability/neural-connectivity--edit",
     "hrm:capability/neural-connectivity--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/peripheral-neuron",
   "type": "cell",
   "name": "Peripheral neuron",
   "system": "Nervous system",
   "kind": "cell",
   "renewal": "regenerative axon",
   "failures": "Transection, diabetic and chemotherapy neuropathy, compression. Axons regrow, slowly and imperfectly.",
   "anchors": [
    "Peripheral nerve regeneration is a genuine biological capability humans retain"
   ],
   "order": 1,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/peripheral-neuron--see",
    "hrm:capability/peripheral-neuron--model",
    "hrm:capability/peripheral-neuron--reach",
    "hrm:capability/peripheral-neuron--edit",
    "hrm:capability/peripheral-neuron--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/cutaneous-sensory-reinnervation",
     "hrm:capability/peripheral-neuron--see",
     "hrm:capability/peripheral-neuron--model",
     "hrm:capability/peripheral-neuron--reach",
     "hrm:capability/peripheral-neuron--edit",
     "hrm:capability/peripheral-neuron--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/photoreceptor-rpe",
   "type": "cell",
   "name": "Photoreceptor / retinal pigment epithelium",
   "system": "Sensory",
   "kind": "cell",
   "renewal": "post-mitotic",
   "failures": "Inherited retinal dystrophy, macular degeneration, photoreceptor death. No human regeneration.",
   "anchors": [
    "Luxturna (voretigene neparvovec), FDA 2017"
   ],
   "order": 2,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/photoreceptor-rpe--see",
    "hrm:capability/photoreceptor-rpe--model",
    "hrm:capability/photoreceptor-rpe--reach",
    "hrm:capability/photoreceptor-rpe--edit",
    "hrm:capability/photoreceptor-rpe--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/photoreceptor-rpe--see",
     "hrm:capability/photoreceptor-rpe--model",
     "hrm:capability/photoreceptor-rpe--reach",
     "hrm:capability/photoreceptor-rpe--edit",
     "hrm:capability/photoreceptor-rpe--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/skeletal-muscle",
   "type": "cell",
   "name": "Skeletal muscle fibre / satellite cell",
   "system": "Musculoskeletal",
   "kind": "cell",
   "renewal": "regenerative",
   "failures": "Dystrophies, sarcopenia with age, denervation atrophy, cachexia.",
   "anchors": [
    "Elevidys (delandistrogene moxeparvovec), FDA 2023"
   ],
   "order": 6,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/skeletal-muscle--see",
    "hrm:capability/skeletal-muscle--model",
    "hrm:capability/skeletal-muscle--reach",
    "hrm:capability/skeletal-muscle--edit",
    "hrm:capability/skeletal-muscle--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/skeletal-muscle--see",
     "hrm:capability/skeletal-muscle--model",
     "hrm:capability/skeletal-muscle--reach",
     "hrm:capability/skeletal-muscle--edit",
     "hrm:capability/skeletal-muscle--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/smooth-muscle",
   "type": "cell",
   "name": "Smooth muscle cell",
   "system": "Cardiovascular",
   "kind": "cell",
   "renewal": "limited",
   "failures": "Phenotype switching in atherosclerosis, airway remodelling, aneurysm wall failure.",
   "anchors": [
    "Smooth muscle phenotype switching drives plaque instability"
   ],
   "order": 3,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/smooth-muscle--see",
    "hrm:capability/smooth-muscle--model",
    "hrm:capability/smooth-muscle--reach",
    "hrm:capability/smooth-muscle--edit",
    "hrm:capability/smooth-muscle--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/smooth-muscle--see",
     "hrm:capability/smooth-muscle--model",
     "hrm:capability/smooth-muscle--reach",
     "hrm:capability/smooth-muscle--edit",
     "hrm:capability/smooth-muscle--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/t-lymphocyte",
   "type": "cell",
   "name": "T lymphocyte",
   "system": "Blood & immune",
   "kind": "cell",
   "renewal": "self-renewing",
   "failures": "Exhaustion, autoreactivity, immunodeficiency, malignancy, age-related repertoire narrowing.",
   "anchors": [
    "Kymriah, FDA 2017",
    "In vivo CAR-T programmes, preclinical to Phase 1"
   ],
   "order": 0,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/t-lymphocyte--see",
    "hrm:capability/t-lymphocyte--model",
    "hrm:capability/t-lymphocyte--reach",
    "hrm:capability/t-lymphocyte--edit",
    "hrm:capability/t-lymphocyte--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/t-lymphocyte--see",
     "hrm:capability/t-lymphocyte--model",
     "hrm:capability/t-lymphocyte--reach",
     "hrm:capability/t-lymphocyte--edit",
     "hrm:capability/t-lymphocyte--verify"
    ]
   }
  },
  {
   "id": "hrm:cell/tissue-architecture",
   "type": "cell",
   "name": "Tissue architecture",
   "system": "Structural & connective",
   "kind": "non-cell",
   "renewal": "none",
   "failures": "Alveolar destruction, nephron loss, cortical disorganisation. A 3-D pattern that cells do not re-derive alone.",
   "anchors": [
    "Organoid self-organisation, in vitro only",
    "Axolotl positional memory literature"
   ],
   "order": 8,
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "review": {
    "state": "ai-proposed"
   },
   "lastChecked": "2026-07-28",
   "capabilities": [
    "hrm:capability/tissue-architecture--see",
    "hrm:capability/tissue-architecture--model",
    "hrm:capability/tissue-architecture--reach",
    "hrm:capability/tissue-architecture--edit",
    "hrm:capability/tissue-architecture--verify"
   ],
   "derivedRelations": {
    "capabilities": [
     "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
     "hrm:capability/mammalian-scar-free-regeneration-target-state",
     "hrm:capability/tissue-architecture--see",
     "hrm:capability/tissue-architecture--model",
     "hrm:capability/tissue-architecture--reach",
     "hrm:capability/tissue-architecture--edit",
     "hrm:capability/tissue-architecture--verify"
    ]
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/acomys-ear-regeneration-independent-replication",
   "statement": "In an unaffiliated laboratory, Acomys cahirinus closed 4 mm ear punches completely within two months in 100% of wounds, regenerating cartilage, adipose, dermis, epidermis, hair follicles, vessels, muscle and nerve, while C57BL/6 mice scarred.",
   "context": {
    "species": "Acomys cahirinus (NCBITaxon:10068)",
    "model": "4 mm full-thickness ear punch",
    "comparator": "C57BL/6 mice"
   },
   "measurement": {
    "measured": "structure",
    "assay": "histology",
    "endpoint": "complete ear-punch closure with tissue regeneration",
    "effect": "100% of punches closed by 2 months with regenerated tissues including muscle and nerve"
   },
   "evidence": [
    {
     "source": "hrm:source/matias-santos-2016-regeneration",
     "design": "animal-controlled",
     "locator": "abstract"
    }
   ],
   "rung": "L2",
   "replicates": [
    "hrm:claim/acomys-regenerates-full-thickness-skin-without-scar"
   ],
   "replication": {
    "independentGroups": 1,
    "note": "Independent of the Seifert/Maden groups; confirms the ear-punch phenotype. Dorsal skin regeneration was not the readout here."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/mammalian-scar-free-regeneration-target-state"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/matias-santos-2016-regeneration"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/acomys-regenerates-full-thickness-skin-without-scar",
   "statement": "Adult African spiny mice (Acomys) regenerate full-thickness dorsal skin wounds and ear punches with hair follicles, sebaceous glands, dermis and cartilage, where laboratory mice heal the same wounds by fibrotic scar.",
   "context": {
    "species": "Acomys (NCBITaxon:10068 and relatives)",
    "model": "skin autotomy wounds; 4 mm ear punch",
    "comparator": "Mus musculus C57BL/6"
   },
   "measurement": {
    "measured": "structure",
    "assay": "histology; mechanical testing",
    "endpoint": "appendage and dermal regeneration in the wound",
    "effect": "complete regeneration of follicles, glands, dermis and cartilage in ear punches; hair follicle regeneration in dorsal wounds"
   },
   "evidence": [
    {
     "source": "hrm:source/seifert-2012-nature",
     "design": "animal-observational",
     "locator": "abstract"
    },
    {
     "source": "hrm:source/brant-2016-wrr",
     "design": "animal-observational",
     "locator": "abstract"
    },
    {
     "source": "hrm:source/maden-2018-burns",
     "design": "animal-controlled",
     "locator": "abstract",
     "note": "extends to full-thickness thermal burns"
    },
    {
     "source": "hrm:source/gawriluk-2016-natcommun",
     "design": "animal-controlled",
     "locator": "abstract",
     "note": "ear-hole closure as a discrete trait across species"
    }
   ],
   "rung": "L2",
   "replication": {
    "independentGroups": 1,
    "note": "The four sources share authorship (Seifert, Maden, Brant). Independent replication is the Matias Santos claim below, which is why this claim's replication count is 1 and not 4."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/mammalian-scar-free-regeneration-target-state"
   ],
   "limitations": [
    "a rodent, so L2 by the ladder even though the finding is a species trait rather than an intervention",
    "mechanism not established by these papers"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/seifert-2012-nature",
     "hrm:source/brant-2016-wrr",
     "hrm:source/maden-2018-burns",
     "hrm:source/gawriluk-2016-natcommun"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "replicatedBy": [
     "hrm:claim/acomys-ear-regeneration-independent-replication"
    ]
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/adult-mammalian-wounds-heal-by-scar",
   "statement": "Adult mammalian and human skin wounds heal by a fibrotic scar that lacks the appendages and matrix organisation of uninjured skin; this is the default outcome of adult repair.",
   "context": {
    "species": "human and mammals generally",
    "model": "full-thickness cutaneous wounds"
   },
   "measurement": {
    "measured": "structure",
    "endpoint": "histological outcome of healed adult wounds",
    "effect": "scar, not regeneration"
   },
   "evidence": [
    {
     "source": "hrm:source/gurtner-2008-nature",
     "design": "review",
     "locator": "abstract"
    },
    {
     "source": "hrm:source/eming-2014-scitranslmed",
     "design": "review",
     "locator": "abstract"
    }
   ],
   "rung": "L5",
   "replication": {
    "independentGroups": 2,
    "note": "Review-level statement of a universal clinical observation."
   },
   "status": {
    "peerReviewed": true
   },
   "contradicts": [
    "hrm:capability/dermal-architecture-regeneration-without-scar"
   ],
   "limitations": [
    "a statement of the problem, cited so that the default outcome is in the graph rather than assumed"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/gurtner-2008-nature",
     "hrm:source/eming-2014-scitranslmed"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/avotermin-improved-scar-appearance-phase-1-2",
   "statement": "Intradermal avotermin (recombinant human TGF-β3) given before and 24 h after wounding improved visual scar scores at 6 and 12 months versus placebo in three double-blind, placebo-controlled, within-participant phase I/II studies in healthy volunteers.",
   "context": {
    "species": "human",
    "model": "1 cm full-thickness incisions in healthy volunteers",
    "intervention": "avotermin 0.25–500 ng/100 µL per linear cm, two doses",
    "comparator": "placebo or standard care, within participant"
   },
   "measurement": {
    "measured": "structure",
    "assay": "blinded visual scar assessment (VAS); total scar score",
    "endpoint": "scar appearance at 6 and 12 months",
    "effect": "median VAS improvement 5 mm at 6 months and 8 mm at 12 months at 50 ng; dose-dependent total-score improvement in the third study"
   },
   "evidence": [
    {
     "source": "hrm:source/ferguson-2009-lancet",
     "design": "rct",
     "locator": "abstract",
     "blinding": "double-blind",
     "randomisation": "within-participant",
     "note": "NCT00847925, NCT00847795, NCT00629811"
    }
   ],
   "rung": "L4",
   "replication": {
    "independentGroups": 0,
    "note": "Sponsor-run (Renovo). The later phase II (McCollum 2011) is the same sponsor."
   },
   "status": {
    "peerReviewed": true,
    "contradicted": true
   },
   "supports": [
    "hrm:capability/pharmacological-scar-reduction-in-humans"
   ],
   "drift": "The sponsor reported in 2011 that the phase 3 programme failed; no peer-reviewed publication of the phase 3 was located as of 2026-09-11, so the published record still reads as a success.",
   "limitations": [
    "small effect sizes on a visual scale",
    "healthy-volunteer incisions, not clinical wounds"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/ferguson-2009-lancet"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "replicatedBy": [
     "hrm:claim/avotermin-phase-2-surgical-scar-improvement"
    ]
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/avotermin-phase-2-surgical-scar-improvement",
   "statement": "A single intradermal dose of avotermin 500 ng/100 µL per linear cm at wound closure improved lay-panel groin scar scores versus placebo in a 156-patient double-blind within-patient phase II trial after varicose-vein surgery.",
   "context": {
    "species": "human",
    "model": "bilateral saphenofemoral ligation wounds",
    "intervention": "avotermin, four doses tested, given once",
    "comparator": "placebo, contralateral leg"
   },
   "measurement": {
    "measured": "structure",
    "assay": "lay-panel total scar score from VAS, 6 weeks to 7 months",
    "endpoint": "scar appearance",
    "effect": "mean lay-panel score difference 16.49 mm at 500 ng, P = 0.036"
   },
   "evidence": [
    {
     "source": "hrm:source/mccollum-2011-bjs",
     "design": "rct",
     "locator": "abstract",
     "n": "156",
     "blinding": "double-blind",
     "randomisation": "within-patient"
    }
   ],
   "rung": "L4",
   "replicates": [
    "hrm:claim/avotermin-improved-scar-appearance-phase-1-2"
   ],
   "replication": {
    "independentGroups": 0,
    "note": "Same sponsor; not an independent replication."
   },
   "status": {
    "peerReviewed": true,
    "contradicted": true
   },
   "supports": [
    "hrm:capability/pharmacological-scar-reduction-in-humans"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/mccollum-2011-bjs"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/b-vec-topical-gene-therapy-closes-deb-wounds",
   "statement": "Weekly topical beremagene geperpavec (HSV-1 vector delivering COL7A1) achieved complete healing in 67% of treated versus 22% of placebo wounds at six months in a 31-patient, double-blind, intrapatient-randomised phase 3 in dystrophic epidermolysis bullosa.",
   "context": {
    "species": "human",
    "model": "dystrophic epidermolysis bullosa (COL7A1 mutations)",
    "intervention": "topical B-VEC, weekly for 26 weeks",
    "comparator": "placebo, matched wound in the same patient",
    "age": "6 months and older"
   },
   "measurement": {
    "measured": "function",
    "assay": "clinical wound assessment",
    "endpoint": "complete wound healing at 6 months (primary)",
    "effect": "67% vs 22%, difference 46 percentage points (95% CI 24–68), P = 0.002",
    "uncertainty": "95% CI 24 to 68 percentage points"
   },
   "evidence": [
    {
     "source": "hrm:source/guide-2022-nejm",
     "design": "rct",
     "locator": "abstract",
     "n": "31 patients, primary wound pairs",
     "blinding": "double-blind",
     "randomisation": "intrapatient 1:1"
    }
   ],
   "rung": "L4",
   "replication": {
    "independentGroups": 0,
    "note": "Single sponsor (Krystal Biotech), multi-site. No unaffiliated trial."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery"
   ],
   "limitations": [
    "vector does not persist; dosing is repeated",
    "one gene, one rare disease"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/guide-2022-nejm"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/cultured-epithelial-autografts-permanently-cover-large-burns",
   "statement": "Sheets of cultured autologous keratinocytes permanently cover large full-thickness burn wounds, and have been used and followed long-term at unaffiliated centres since the first report.",
   "context": {
    "species": "human",
    "model": "large full-thickness burns",
    "intervention": "cultured epithelial autograft"
   },
   "measurement": {
    "measured": "function",
    "assay": "clinical follow-up",
    "endpoint": "permanent wound coverage",
    "effect": "permanent take of cultured epithelium on extensive burns (first report, two patients); long-term coverage in later series"
   },
   "evidence": [
    {
     "source": "hrm:source/gallico-1984-nejm",
     "design": "case-series",
     "locator": "abstract",
     "n": "2",
     "note": "originating report (Green laboratory)"
    },
    {
     "source": "hrm:source/sood-2000-jbcr",
     "design": "case-series",
     "locator": "abstract",
     "note": "long-term follow-up at a separate centre"
    },
    {
     "source": "hrm:source/sun-2014-science",
     "design": "review",
     "locator": "abstract",
     "note": "surveys clinical use of cultured epithelium"
    }
   ],
   "rung": "L5",
   "replication": {
    "independentGroups": 2,
    "note": "Founding report plus a separate centre's series and a review; fragility and absence of dermis are consistent across them."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/epidermis-replacement-cultured-autograft"
   ],
   "limitations": [
    "epidermis only; no dermis, appendages or normal sensation",
    "fragile skin prone to blistering"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/gallico-1984-nejm",
     "hrm:source/sood-2000-jbcr",
     "hrm:source/sun-2014-science"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/cyclic-partial-reprogramming-ameliorates-aging-in-mice",
   "statement": "Short-term cyclic expression of OSKM in vivo ameliorated cellular and physiological hallmarks of aging and prolonged lifespan in a progeroid mouse model, and improved recovery from metabolic disease and muscle injury in aged wild-type mice, without teratoma formation.",
   "context": {
    "species": "mouse (NCBITaxon:10090)",
    "model": "LAKI progeria model; aged wild-type mice",
    "intervention": "cyclic doxycycline-induced OSKM"
   },
   "measurement": {
    "measured": "function",
    "assay": "aging hallmarks; lifespan; injury recovery",
    "endpoint": "lifespan and recovery",
    "effect": "prolonged lifespan in progeroid mice; improved recovery in aged mice"
   },
   "evidence": [
    {
     "source": "hrm:source/ocampo-2016-cell",
     "design": "animal-controlled",
     "locator": "abstract"
    }
   ],
   "rung": "L2",
   "replication": {
    "independentGroups": 0,
    "note": "One group (Izpisua Belmonte). Later partial-reprogramming studies by other groups exist but are not cited here."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
    "hrm:capability/cell-identity-retention-under-partial-reprogramming"
   ],
   "limitations": [
    "progeroid model for the lifespan result",
    "safe expression window narrow; continuous expression is lethal in the same system"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/ocampo-2016-cell"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/dermagraft-raises-diabetic-ulcer-closure",
   "statement": "Dermagraft, a human fibroblast-derived dermal substitute, raised complete closure of chronic diabetic foot ulcers by 12 weeks to 30.0% versus 18.3% with conventional therapy in a 35-centre randomised trial of 314 patients.",
   "context": {
    "species": "human",
    "model": "chronic diabetic foot ulcer of >6 weeks",
    "intervention": "Dermagraft",
    "comparator": "conventional therapy with pressure-reducing footwear"
   },
   "measurement": {
    "measured": "function",
    "endpoint": "complete wound closure by week 12",
    "effect": "30.0% (39/130) vs 18.3% (21/115), P = 0.023"
   },
   "evidence": [
    {
     "source": "hrm:source/marston-2003-diabetescare",
     "design": "rct",
     "locator": "abstract",
     "n": "314",
     "randomisation": "randomised, multicentre"
    }
   ],
   "rung": "L4",
   "replication": {
    "independentGroups": 0,
    "note": "Sponsor-run (Advanced Tissue Sciences/Smith & Nephew). Together with the Graftskin trial it establishes the capability at L5: two unaffiliated sponsors, two living constructs, same direction of effect."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/dermal-substitute-for-chronic-wound-closure"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/marston-2003-diabetescare"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/en1-lineage-fibroblasts-produce-scar",
   "statement": "A distinct dermal fibroblast lineage marked by Engrailed-1 expression carries intrinsic fibrogenic potential and is responsible for the bulk of scar formation in mouse skin wounds.",
   "context": {
    "species": "mouse (NCBITaxon:10090)",
    "model": "dorsal skin wounds; lineage tracing and transplantation",
    "cellType": "dermal fibroblast"
   },
   "measurement": {
    "measured": "structure",
    "assay": "lineage tracing; transplantation; ablation",
    "endpoint": "contribution of the lineage to scar matrix",
    "effect": "the Engrailed-1 lineage produces the majority of connective tissue in scar; its ablation reduces scarring"
   },
   "evidence": [
    {
     "source": "hrm:source/rinkevich-2015-science",
     "design": "animal-controlled",
     "locator": "abstract"
    },
    {
     "source": "hrm:source/driskell-2013-nature",
     "design": "animal-controlled",
     "locator": "abstract",
     "note": "establishes distinct fibroblast lineages determining dermal architecture"
    }
   ],
   "rung": "L2",
   "replication": {
    "independentGroups": 2,
    "note": "Two groups (Longaker/Weissman; Watt) describing lineage heterogeneity with different markers; the Engrailed-1 result itself is one group."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/fibrogenic-fibroblast-lineage-control"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/rinkevich-2015-science",
     "hrm:source/driskell-2013-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G2",
   "id": "hrm:claim/fda-approved-b-vec-2023",
   "statement": "The U.S. FDA approved beremagene geperpavec (Vyjuvek) on 19 May 2023 for wounds in patients six months and older with dystrophic epidermolysis bullosa, citing 65% versus 26% complete wound closure at 24 weeks in a 31-patient randomised placebo-controlled trial.",
   "context": {
    "species": "human",
    "model": "dystrophic epidermolysis bullosa",
    "intervention": "topical B-VEC"
   },
   "measurement": {
    "measured": "function",
    "endpoint": "complete wound closure at 24 weeks (FDA summary)",
    "effect": "65% vs 26% (FDA summary; the NEJM primary analysis reports 67% vs 22% at 6 months — different analysis, same trial)"
   },
   "evidence": [
    {
     "source": "hrm:source/fda-2023-vyjuvek",
     "design": "regulatory-decision",
     "locator": "press announcement, efficacy paragraph",
     "quote": "Sixty-five percent of the Vyjuvek-treated wounds completely closed while only 26% of the placebo-treated wound completely closed"
    }
   ],
   "rung": "L4",
   "replication": {
    "independentGroups": 0,
    "note": "A regulatory decision on the sponsor's trial; not a replication."
   },
   "status": {
    "peerReviewed": false
   },
   "supports": [
    "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/fda-2023-vyjuvek"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/fetal-skin-heals-without-scar",
   "statement": "Early-gestation fetal skin, human and animal, heals full-thickness wounds without scar; the transition to scar-forming healing occurs in late gestation and is associated with differences in inflammation, growth-factor profile and extracellular matrix.",
   "context": {
    "species": "human and mammalian fetus",
    "model": "fetal cutaneous wounds"
   },
   "measurement": {
    "measured": "structure",
    "endpoint": "histological regeneration versus scar",
    "effect": "scarless regeneration in early gestation; scar after the transition"
   },
   "evidence": [
    {
     "source": "hrm:source/larson-2010-prs",
     "design": "review",
     "locator": "abstract"
    }
   ],
   "rung": "L5",
   "replication": {
    "independentGroups": 2,
    "note": "Review-level synthesis of many groups' observations; primary fetal-surgery series are not attached here."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/fetal-scarless-healing-target-state"
   ],
   "limitations": [
    "an observation of a developmental state, not an intervention"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/larson-2010-prs"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/graftskin-raises-diabetic-ulcer-closure",
   "statement": "Graftskin, a living bilayered skin equivalent, raised complete healing of neuropathic diabetic foot ulcers at 12 weeks to 56% versus 38% with saline-moistened gauze in a 24-centre randomised trial of 208 patients.",
   "context": {
    "species": "human",
    "model": "noninfected, nonischaemic chronic plantar diabetic foot ulcer",
    "intervention": "Graftskin applied weekly up to 5 times",
    "comparator": "saline-moistened gauze with standard debridement and off-loading"
   },
   "measurement": {
    "measured": "function",
    "endpoint": "complete wound healing at 12 weeks, intention to treat",
    "effect": "56% (63/112) vs 38% (36/96), P = 0.0042; median time to closure 65 vs 90 days; odds ratio 2.14",
    "uncertainty": "OR 95% CI 1.23–3.74"
   },
   "evidence": [
    {
     "source": "hrm:source/veves-2001-diabetescare",
     "design": "rct",
     "locator": "abstract",
     "n": "208",
     "randomisation": "randomised, multicentre"
    }
   ],
   "rung": "L4",
   "replication": {
    "independentGroups": 0,
    "note": "Sponsor-run (Organogenesis). The unaffiliated Dermagraft trial is a different product, so it corroborates the capability, not this claim."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/dermal-substitute-for-chronic-wound-closure"
   ],
   "limitations": [
    "closure endpoint only; scar quality, appendages and sensation not measured"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/veves-2001-diabetescare"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/hpsc-skin-organoids-form-hair-bearing-skin-in-mice",
   "statement": "Human pluripotent stem-cell-derived skin organoids develop stratified epidermis, fat-rich dermis, pigmented hair follicles with sebaceous glands and Merkel-targeting sensory neurons over 4–5 months, and form planar hair-bearing skin when grafted onto nude mice.",
   "context": {
    "species": "human cells; nude mouse host",
    "model": "organoid culture; xenograft",
    "intervention": "stepwise TGF-β and FGF modulation"
   },
   "measurement": {
    "measured": "structure",
    "assay": "histology; single-cell RNA-seq versus fetal skin; grafting",
    "endpoint": "appendage-bearing skin formation",
    "effect": "organoids equivalent to second-trimester facial skin; hair-bearing planar skin after grafting"
   },
   "evidence": [
    {
     "source": "hrm:source/lee-2020-nature",
     "design": "animal-controlled",
     "locator": "abstract"
    }
   ],
   "rung": "L2",
   "replication": {
    "independentGroups": 0,
    "note": "One group (Koehler). Human cells, mouse host: nothing grafted into a person."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
    "hrm:capability/cutaneous-sensory-reinnervation"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/lee-2020-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/iv-aav9-human-cns-transduction-rests-on-two-autopsies",
   "statement": "Direct evidence that intravenous AAV9 (onasemnogene abeparvovec) transduces the human central nervous system rests on post-mortem tissue from two treated infants, with vector genomes in liver hundreds-fold higher than in CNS.",
   "context": {
    "species": "human",
    "model": "spinal muscular atrophy, infants",
    "intervention": "single intravenous AAV9 dose",
    "route": "intravenous"
   },
   "measurement": {
    "measured": "transduction",
    "assay": "vector DNA, mRNA and SMN protein in post-mortem tissue",
    "endpoint": "CNS biodistribution",
    "effect": "vector detected in CNS at levels far below liver; n=2"
   },
   "evidence": [
    {
     "source": "hrm:source/thomsen-2021-natmed",
     "design": "case-series",
     "locator": "abstract",
     "n": "2"
    }
   ],
   "rung": "L4",
   "replication": {
    "independentGroups": 0,
    "note": "Sponsor-affiliated analysis; clinical benefit in SMA is replicated, CNS transduction evidence is not."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/systemic-cell-type-specific-delivery"
   ],
   "drift": "'Proves IV AAV9 transduces human CNS' — two autopsies; clinical benefit is offered as transduction evidence, but it is not.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/thomsen-2021-natmed"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/myofibroblasts-regenerate-adipocytes-in-mouse-wounds",
   "statement": "During wound-induced hair neogenesis in mice, scar-forming myofibroblasts convert into adipocytes, dependent on BMP signalling from the new hair follicles.",
   "context": {
    "species": "mouse (NCBITaxon:10090)",
    "model": "large full-thickness wounds with hair neogenesis",
    "cellType": "myofibroblast"
   },
   "measurement": {
    "measured": "structure",
    "assay": "lineage tracing; BMP pathway manipulation",
    "endpoint": "adipocyte regeneration from myofibroblast lineage",
    "effect": "myofibroblasts adopt adipocyte fate in regenerating wounds"
   },
   "evidence": [
    {
     "source": "hrm:source/plikus-2017-science",
     "design": "animal-controlled",
     "locator": "abstract"
    }
   ],
   "rung": "L2",
   "replication": {
    "independentGroups": 0,
    "note": "One collaboration (Plikus/Cotsarelis). No independent replication cited."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/dermal-adipocyte-regeneration",
    "hrm:capability/hair-follicle-neogenesis-after-wounding"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/plikus-2017-science"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/neurotrophins-enhance-angiogenesis-in-engineered-skin",
   "statement": "In a human tissue-engineered skin model, nerve growth factor, BDNF, NT-3 and GDNF enhanced angiogenesis, coupling innervation signals to vascular growth in vitro.",
   "context": {
    "species": "human cells in vitro",
    "model": "tissue-engineered skin with endothelial cells",
    "intervention": "neurotrophic factors"
   },
   "measurement": {
    "measured": "structure",
    "assay": "capillary-like network formation",
    "endpoint": "angiogenesis in the construct",
    "effect": "increased capillary-like network formation with neurotrophins"
   },
   "evidence": [
    {
     "source": "hrm:source/blais-2013-tissueeng",
     "design": "in-vitro",
     "locator": "abstract"
    }
   ],
   "rung": "L1",
   "replication": {
    "independentGroups": 0
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/cutaneous-sensory-reinnervation"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/blais-2013-tissueeng"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/no-therapy-reverses-established-fibrosis",
   "statement": "No approved therapy reverses established organ fibrosis; current antifibrotic drugs slow progression, and fibrosis remains a major cause of irreversible organ dysfunction.",
   "context": {
    "species": "human",
    "model": "fibrotic disease across organs"
   },
   "measurement": {
    "measured": "none",
    "endpoint": "reversal of established fibrosis",
    "effect": "not achieved by any approved therapy"
   },
   "evidence": [
    {
     "source": "hrm:source/henderson-2020-nature",
     "design": "review",
     "locator": "abstract"
    }
   ],
   "rung": "L0",
   "replication": {
    "independentGroups": 1,
    "note": "Review-level statement of the field's position."
   },
   "status": {
    "peerReviewed": true
   },
   "contradicts": [
    "hrm:capability/established-dermal-scar-reversal"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/henderson-2020-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/osk-reprogramming-restores-vision-in-mice",
   "statement": "Ectopic expression of Oct4, Sox2 and Klf4 in mouse retinal ganglion cells restored youthful DNA-methylation patterns and transcriptomes, promoted axon regeneration after injury, and reversed vision loss in a glaucoma model and in aged mice, dependent on TET1/TET2.",
   "context": {
    "species": "mouse (NCBITaxon:10090)",
    "model": "optic nerve crush; glaucoma model; aged mice",
    "cellType": "retinal ganglion cell",
    "intervention": "AAV-delivered inducible OSK"
   },
   "measurement": {
    "measured": "function",
    "assay": "DNA methylation age; transcriptomics; axon regeneration; visual acuity",
    "endpoint": "vision restoration",
    "effect": "reversal of vision loss in glaucoma and aged mice"
   },
   "evidence": [
    {
     "source": "hrm:source/lu-2020-nature",
     "design": "animal-controlled",
     "locator": "abstract"
    }
   ],
   "rung": "L2",
   "replication": {
    "independentGroups": 0,
    "note": "One group (Sinclair). Independent replication not cited here."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
    "hrm:capability/cell-identity-retention-under-partial-reprogramming"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/lu-2020-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/synthetic-fibrin-crosslinker-induces-haemostasis-in-rodents",
   "statement": "A synthetic polymer that cross-links fibrin modulated clot properties and induced haemostasis in rodent models of bleeding.",
   "context": {
    "species": "rodent",
    "model": "bleeding and trauma models",
    "intervention": "intravenous synthetic fibrin cross-linking polymer"
   },
   "measurement": {
    "measured": "function",
    "endpoint": "blood loss and survival",
    "effect": "reduced blood loss / improved haemostasis versus control"
   },
   "evidence": [
    {
     "source": "hrm:source/chan-2015-scitranslmed",
     "design": "animal-controlled",
     "locator": "abstract"
    }
   ],
   "rung": "L2",
   "replication": {
    "independentGroups": 0
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/synthetic-haemostat-for-noncompressible-haemorrhage"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/chan-2015-scitranslmed"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/thick-engineered-tissue-vascularisation-unsolved",
   "statement": "Vascularisation of engineered tissue beyond the diffusion limit remains an unsolved problem: prevascularisation and angiogenic strategies yield capillary networks in rodent constructs but not organised, stable, clinically usable vasculature in thick human tissue.",
   "context": {
    "species": "multiple",
    "model": "engineered and regenerated tissues"
   },
   "measurement": {
    "measured": "none",
    "endpoint": "clinically usable perfused vasculature in thick constructs",
    "effect": "not achieved"
   },
   "evidence": [
    {
     "source": "hrm:source/rouwkema-2016-trendsbiotech",
     "design": "review",
     "locator": "abstract"
    },
    {
     "source": "hrm:source/laschke-2016-biotechadv",
     "design": "review",
     "locator": "abstract"
    }
   ],
   "rung": "L2",
   "replication": {
    "independentGroups": 2,
    "note": "Two independent reviews reaching the same assessment."
   },
   "status": {
    "peerReviewed": true
   },
   "contradicts": [
    "hrm:capability/organised-microvascular-network-in-regenerated-dermis"
   ],
   "limitations": [
    "reviews; the rung L2 reflects the best demonstrations they survey (rodent)"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/rouwkema-2016-trendsbiotech",
     "hrm:source/laschke-2016-biotechadv"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/transgenic-epidermal-stem-cells-regenerate-functional-epidermis-jeb",
   "statement": "Autologous epidermal stem cells corrected with a retroviral vector regenerated a durable, functional, self-renewing epidermis in patients with junctional epidermolysis bullosa: nine grafts on an adult's legs stable at one year (2006), and an entire epidermis on ~80% of a child's body surface (2017).",
   "context": {
    "species": "human",
    "model": "junctional epidermolysis bullosa (LAMB3 mutations)",
    "intervention": "ex vivo retroviral LAMB3 correction of epidermal stem cells; cultured grafts",
    "comparator": "none (single patients)"
   },
   "measurement": {
    "measured": "function",
    "assay": "clinical follow-up; integration-site analysis; clonal tracing",
    "endpoint": "stable, blister-free, adherent epidermis",
    "effect": "full functional correction of grafted areas; maintained by a defined repertoire of transduced stem cells"
   },
   "evidence": [
    {
     "source": "hrm:source/mavilio-2006-natmed",
     "design": "case-report",
     "locator": "abstract",
     "n": "1"
    },
    {
     "source": "hrm:source/hirsch-2017-nature",
     "design": "case-report",
     "locator": "abstract",
     "n": "1"
    }
   ],
   "rung": "L4",
   "replication": {
    "independentGroups": 0,
    "note": "Both patients treated by the same group (De Luca). Two successes, no independent replication — L4, not L5."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/epidermis-gene-corrected-stem-cell-replacement"
   ],
   "drift": "'Boy given new skin' — the regenerated organ is the epidermis; the dermis was his own.",
   "wouldMove": "An unaffiliated centre reproducing durable engraftment, with integration-site surveillance beyond five years.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/mavilio-2006-natmed",
     "hrm:source/hirsch-2017-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/wound-induced-hair-neogenesis-in-adult-mice",
   "statement": "Adult mice regenerate new hair follicles de novo in the centre of large full-thickness wounds through a Wnt-dependent process resembling embryonic follicle development.",
   "context": {
    "species": "mouse (NCBITaxon:10090)",
    "model": "large (>1 cm) full-thickness excisional wounds",
    "comparator": "small wounds; Wnt inhibition"
   },
   "measurement": {
    "measured": "structure",
    "assay": "histology; lineage tracing; Wnt reporter",
    "endpoint": "de novo follicle formation in healed wound",
    "effect": "new follicles form in large wounds; blocked by Wnt inhibition, enhanced by Wnt"
   },
   "evidence": [
    {
     "source": "hrm:source/ito-2007-nature",
     "design": "animal-controlled",
     "locator": "abstract"
    }
   ],
   "rung": "L2",
   "replication": {
    "independentGroups": 1,
    "note": "Widely reproduced in mice since (not cited here); no human report located."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/hair-follicle-neogenesis-after-wounding"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/ito-2007-nature"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "claim",
   "grounding": "G1",
   "id": "hrm:claim/yap-inhibition-yields-mouse-wound-regeneration",
   "statement": "Blocking mechanotransduction with verteporfin (a YAP inhibitor) or fibroblast-specific YAP knockout prevents Engrailed-1 activation in mouse wounds and produces regeneration with recovery of skin appendages, matrix ultrastructure and mechanical strength.",
   "context": {
    "species": "mouse (NCBITaxon:10090)",
    "model": "full-thickness dorsal excisional wounds",
    "intervention": "local verteporfin; fibroblast-specific YAP knockout",
    "comparator": "vehicle; wild type"
   },
   "measurement": {
    "measured": "structure",
    "assay": "histology; electron microscopy; tensile testing; lineage tracing",
    "endpoint": "appendage recovery, ultrastructure, mechanical strength",
    "effect": "regenerative rather than fibrotic outcome in treated wounds"
   },
   "evidence": [
    {
     "source": "hrm:source/mascharak-2021-science",
     "design": "animal-controlled",
     "locator": "abstract"
    }
   ],
   "rung": "L2",
   "replication": {
    "independentGroups": 0,
    "note": "One group (Longaker, Stanford). No independent replication located as of 2026-09-11."
   },
   "status": {
    "peerReviewed": true
   },
   "supports": [
    "hrm:capability/dermal-architecture-regeneration-without-scar",
    "hrm:capability/native-ecm-organisation-reconstruction",
    "hrm:capability/fibrogenic-fibroblast-lineage-control"
   ],
   "drift": "'A drug that heals wounds without scars' — in mice, splinted, one laboratory; verteporfin's human anti-scarring effect is untested.",
   "wouldMove": "Replication by an unaffiliated group, then a large-animal model.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11",
    "evidenceAccessed": [
     "hrm:source/mascharak-2021-science"
    ]
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "experiment",
   "id": "hrm:experiment/acomys-vs-mus-matched-wound-atlas",
   "name": "Matched single-cell and spatial atlas of Acomys versus Mus wound healing",
   "tests": [
    "hrm:question/what-limits-regeneration-in-mus-and-human"
   ],
   "status": "proposed",
   "design": {
    "species": "Acomys cahirinus (NCBITaxon:10068) and Mus musculus (NCBITaxon:10090)",
    "model": "identical full-thickness dorsal wounds",
    "intervention": "none (comparative)",
    "comparator": "species",
    "readout": "single-cell RNA and spatial transcriptomics of immune and fibroblast compartments at days 1, 3, 7, 14, 28; lineage tracing where tools exist",
    "duration": "6–9 months",
    "n": "3–5 animals per species per timepoint"
   },
   "discriminates": "Divergence appearing first in immune populations, in fibroblast lineage composition, or in matrix genes points at which hypothesis to perturb next.",
   "feasibility": {
    "costClass": "medium",
    "durationClass": "months",
    "requires": [
     "Acomys colony",
     "single-cell and spatial sequencing"
    ],
    "ethics": "animal ethics approval"
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "experiment",
   "id": "hrm:experiment/er-100-phase-1-optic-neuropathies",
   "name": "ER-100 (OSK partial epigenetic reprogramming) Phase 1 in open-angle glaucoma and NAION",
   "tests": [
    "hrm:question/partial-reprogramming-human-safety"
   ],
   "status": "running",
   "registration": "NCT07290244",
   "design": {
    "species": "human",
    "model": "open-angle glaucoma; non-arteritic anterior ischaemic optic neuropathy",
    "intervention": "ER-100: controlled expression of OCT4, SOX2, KLF4 in one eye",
    "comparator": "not stated in the sponsor announcement",
    "readout": "safety and tolerability (primary); visual function (secondary)",
    "duration": "not stated",
    "n": "not stated"
   },
   "discriminates": "A safety signal or a visual-function change in the treated eye is the first human data point for the rejuvenation map; absence of harm alone does not demonstrate rejuvenation.",
   "feasibility": {
    "costClass": "high",
    "durationClass": "years",
    "requires": [
     "sponsor-run trial"
    ],
    "ethics": "IND cleared (sponsor statement)"
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "experiment",
   "id": "hrm:experiment/gene-corrected-epidermal-graft-long-term-registry",
   "name": "Long-term registry and integration-site surveillance of gene-corrected epidermal graft recipients",
   "tests": [
    "hrm:question/gene-corrected-epidermal-graft-long-term-safety"
   ],
   "status": "proposed",
   "design": {
    "species": "human",
    "model": "treated JEB patients and any future recipients",
    "intervention": "none (observational)",
    "comparator": "untreated skin of the same patients",
    "readout": "integration-site analysis, clonal dominance, malignancy, graft stability at 5, 10, 15 years",
    "duration": "10+ years",
    "n": "all recipients"
   },
   "discriminates": "Stable polyclonal maintenance without malignancy supports wider use; clonal dominance or transformation changes the risk calculus for every ex vivo integrating vector.",
   "feasibility": {
    "costClass": "low",
    "durationClass": "years",
    "requires": [
     "access to treated patients",
     "integration-site sequencing"
    ],
    "ethics": "consent for long-term follow-up"
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "experiment",
   "id": "hrm:experiment/skin-substitute-scar-quality-rct",
   "name": "Randomised trial of a bioengineered skin substitute with scar quality as the primary endpoint",
   "tests": [
    "hrm:question/skin-substitutes-improve-scar-quality-not-just-closure"
   ],
   "status": "proposed",
   "design": {
    "species": "human",
    "model": "acute full-thickness surgical wounds or chronic ulcers",
    "intervention": "living bioengineered skin substitute",
    "comparator": "standard care",
    "readout": "POSAS observer and patient scores at 12 months; appendage presence and nerve-fibre density on optional biopsy",
    "duration": "18 months",
    "n": "powered for a POSAS difference; to be calculated"
   },
   "discriminates": "Improved scar quality means the constructs do more than accelerate closure; no difference means the capability is closure only.",
   "feasibility": {
    "costClass": "high",
    "durationClass": "years",
    "requires": [
     "multi-centre wound-care network",
     "an unaffiliated sponsor"
    ],
    "ethics": "human research ethics approval"
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "experiment",
   "id": "hrm:experiment/verteporfin-porcine-full-thickness-wound",
   "name": "YAP inhibition (verteporfin) in a splinted porcine full-thickness wound model",
   "tests": [
    "hrm:question/en1-inhibition-translates-to-human-skin"
   ],
   "status": "proposed",
   "design": {
    "species": "pig (NCBITaxon:9823)",
    "model": "splinted full-thickness excisional dorsal wounds, paired within animal",
    "intervention": "local verteporfin at wounding and during proliferation, dose-ranging",
    "comparator": "vehicle, contralateral wound",
    "readout": "appendage count per area, collagen ultrastructure (SEM), tensile strength, closure time at 8 and 16 weeks",
    "duration": "4 months",
    "n": "8–12 animals, paired wounds"
   },
   "discriminates": "Appendages plus native ultrastructure in treated wounds favours conservation; closure without appendages favours the 'regeneration without neogenesis' hypothesis; no difference favours non-translation.",
   "feasibility": {
    "costClass": "medium",
    "durationClass": "months",
    "requires": [
     "large-animal surgical facility",
     "SEM histology",
     "the compound (approved for ophthalmic use)"
    ],
    "ethics": "animal ethics approval"
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "type": "experiment",
   "id": "hrm:experiment/wihn-human-xenograft-large-wound",
   "name": "Test wound-induced hair neogenesis in adult human skin xenografts after large excision",
   "tests": [
    "hrm:question/wound-induced-hair-neogenesis-in-human-skin"
   ],
   "status": "proposed",
   "design": {
    "species": "human skin on immunodeficient mouse",
    "model": "adult human skin xenografts with large full-thickness excisional wounds",
    "intervention": "wound size series with and without Wnt agonism",
    "comparator": "small wounds; untreated",
    "readout": "de novo follicles distinguished from surviving follicles by lineage and position",
    "duration": "6 months",
    "n": "skin from 5+ donors"
   },
   "discriminates": "Neogenesis in human skin with Wnt support shows competence is retained; none under any condition supports postnatal loss.",
   "feasibility": {
    "costClass": "medium",
    "durationClass": "months",
    "requires": [
     "human skin donors",
     "immunodeficient mice"
    ],
    "ethics": "human tissue and animal ethics"
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   }
  },
  {
   "id": "hrm:goal/established-scar-repair",
   "type": "goal",
   "name": "Repair of an established scar",
   "parent": "hrm:goal/universal-repair",
   "description": "Convert a mature fibrotic dermal scar — one that already exists — back into dermis with native matrix organisation, appendages and function. Distinct from preventing scar in a fresh injury: prevention helps the next wound, reversal helps everyone already scarred, and every fibrotic organ shares the problem.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "existenceProof": "None located for dermis. Spiny mice regenerate rather than scar, but no reversal of an already-formed mammalian scar is cited on this map.",
   "requires": [
    {
     "all": [
      "hrm:capability/established-dermal-scar-reversal",
      "hrm:capability/native-ecm-organisation-reconstruction",
      "hrm:capability/organised-microvascular-network-in-regenerated-dermis",
      "hrm:capability/cutaneous-sensory-reinnervation"
     ]
    },
    {
     "any": [
      "hrm:capability/hair-follicle-neogenesis-after-wounding",
      "hrm:capability/appendage-bearing-skin-from-pluripotent-cells"
     ],
     "note": "Appendages must come from somewhere: neogenesis in the remodelled tissue or a graft."
    }
   ],
   "blockedBy": [
    "hrm:question/established-scar-remodelling-to-native-architecture"
   ],
   "informationLimited": false,
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blockedBy": [
     "hrm:question/established-scar-remodelling-to-native-architecture"
    ],
    "enables": [
     "hrm:goal/universal-repair"
    ]
   }
  },
  {
   "type": "goal",
   "id": "hrm:goal/rejuvenation",
   "name": "Rejuvenation",
   "description": "Return an aged person toward their healthiest attainable youthful physiology — function, resilience and regenerative capacity — while preserving identity, memory, learned ability and agency. Not 'the youngest possible state': a constrained optimisation whose target is a body that has never existed before (young molecular state, your memories).",
   "projections": [
    "rejuvenation"
   ],
   "requires": [
    {
     "all": [
      "hrm:goal/systemic-rejuvenation"
     ]
    }
   ],
   "informationLimited": false,
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "children": [
     "hrm:goal/systemic-rejuvenation"
    ],
    "blockedBy": [
     "hrm:question/healthy-target-state-for-aged-tissue"
    ]
   },
   "blockedBy": [
    "hrm:question/healthy-target-state-for-aged-tissue"
   ]
  },
  {
   "type": "goal",
   "id": "hrm:goal/scarless-skin-repair",
   "name": "Scarless functional repair of adult human skin",
   "parent": "hrm:goal/universal-repair",
   "description": "After a full-thickness skin injury in an adult human, restore the skin to its uninjured architecture and function: epidermis, dermis with native extracellular-matrix organisation, microvasculature, sensory innervation, hair follicles and glands, pigmentation, elasticity and barrier — without a persistent fibrotic scar. The first proving ground: it sits across both maps (wounds, burns and surgery above; fibrosis, matrix aging and immune aging below).",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "existenceProof": "Early-gestation fetal skin heals without scar (Larson 2010); adult spiny mice (Acomys) regenerate full-thickness skin with follicles and no scar (Seifert 2012; Matias Santos 2016, independent group); adult laboratory mice regenerate follicles in large wounds (Ito 2007) and, with mechanotransduction blocked, regenerate dermis with appendages and native ultrastructure (Mascharak 2021).",
   "requires": [
    {
     "all": [
      "hrm:goal/skin-immediate-stabilisation",
      "hrm:goal/skin-contamination-control",
      "hrm:goal/skin-structural-reconstruction",
      "hrm:goal/skin-biological-control",
      "hrm:goal/skin-functional-restoration"
     ]
    }
   ],
   "testSuite": [
    {
     "scenario": "small acute wound closes",
     "state": "routine"
    },
    {
     "scenario": "chronic ulcer closes",
     "state": "partial",
     "note": "bioengineered skin substitutes raise closure rates (Veves 2001; Marston 2003) but do not regenerate appendages"
    },
    {
     "scenario": "large burn covered permanently",
     "state": "partial",
     "note": "cultured epithelial autografts since 1984; dermis, appendages and sensation not restored"
    },
    {
     "scenario": "inherited skin disease corrected in situ",
     "state": "partial",
     "note": "one approved topical gene therapy (B-VEC, 2023); one group's transgenic stem-cell grafts (n=2)"
    },
    {
     "scenario": "full-thickness wound regenerates with follicles, glands, nerves and native matrix, no scar",
     "state": "unsolved",
     "note": "shown in mouse (Mascharak 2021) and spiny mouse; no human or large-animal evidence located"
    }
   ],
   "blockedBy": [
    "hrm:question/en1-inhibition-translates-to-human-skin",
    "hrm:question/what-limits-regeneration-in-mus-and-human"
   ],
   "informationLimited": false,
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blockedBy": [
     "hrm:question/en1-inhibition-translates-to-human-skin",
     "hrm:question/what-limits-regeneration-in-mus-and-human"
    ],
    "children": [
     "hrm:goal/skin-biological-control",
     "hrm:goal/skin-contamination-control",
     "hrm:goal/skin-functional-restoration",
     "hrm:goal/skin-immediate-stabilisation",
     "hrm:goal/skin-structural-reconstruction"
    ],
    "enables": [
     "hrm:goal/universal-repair"
    ]
   }
  },
  {
   "type": "goal",
   "id": "hrm:goal/skin-biological-control",
   "name": "Biological control of the repair programme",
   "parent": "hrm:goal/scarless-skin-repair",
   "description": "Steer inflammation, fibroblast fate, proliferation, matrix deposition and morphogenesis toward regeneration rather than fibrosis.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "requires": [
    {
     "all": [
      "hrm:capability/fibrogenic-fibroblast-lineage-control",
      "hrm:capability/inflammation-phase-control-for-regeneration",
      "hrm:capability/pharmacological-scar-reduction-in-humans",
      "hrm:capability/mammalian-scar-free-regeneration-target-state",
      "hrm:capability/fetal-scarless-healing-target-state"
     ]
    }
   ],
   "blockedBy": [
    "hrm:question/what-limits-regeneration-in-mus-and-human",
    "hrm:question/why-avotermin-phase-3-failed"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/scarless-skin-repair"
    ],
    "blockedBy": [
     "hrm:question/why-avotermin-phase-3-failed",
     "hrm:question/what-limits-regeneration-in-mus-and-human"
    ]
   }
  },
  {
   "type": "goal",
   "id": "hrm:goal/skin-contamination-control",
   "name": "Contamination control",
   "parent": "hrm:goal/scarless-skin-repair",
   "description": "Remove foreign material and eliminate pathogens, including established biofilm, without damaging the tissue that must regenerate.",
   "projections": [
    "universal-repair"
   ],
   "requires": [
    {
     "all": [
      "hrm:capability/acute-wound-infection-control",
      "hrm:capability/chronic-wound-biofilm-eradication"
     ]
    }
   ],
   "blockedBy": [
    "hrm:question/reliable-biofilm-eradication-in-chronic-wounds"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/scarless-skin-repair"
    ],
    "blockedBy": [
     "hrm:question/reliable-biofilm-eradication-in-chronic-wounds"
    ]
   }
  },
  {
   "type": "goal",
   "id": "hrm:goal/skin-functional-restoration",
   "name": "Functional restoration and verification",
   "parent": "hrm:goal/scarless-skin-repair",
   "description": "Confirm that regenerated skin has sensation, elasticity, pigmentation and barrier function, and that no fibrotic scar persists. (Remodelling a scar that already exists is a separate goal: established-scar-repair.)",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "requires": [
    {
     "all": [
      "hrm:capability/wound-bed-assessment-in-vivo",
      "hrm:capability/fibroblast-state-sensing-in-living-wound",
      "hrm:capability/regeneration-verification-histology-and-scar-scales"
     ]
    }
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/scarless-skin-repair"
    ]
   }
  },
  {
   "type": "goal",
   "id": "hrm:goal/skin-immediate-stabilisation",
   "name": "Immediate stabilisation of a skin injury",
   "parent": "hrm:goal/scarless-skin-repair",
   "description": "In the first minutes: stop bleeding and restore a barrier so that nothing irrecoverable is lost while repair is organised.",
   "projections": [
    "universal-repair"
   ],
   "requires": [
    {
     "all": [
      "hrm:capability/skin-haemostasis",
      "hrm:capability/temporary-barrier-restoration"
     ]
    }
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/scarless-skin-repair"
    ]
   }
  },
  {
   "type": "goal",
   "id": "hrm:goal/skin-structural-reconstruction",
   "name": "Structural reconstruction of skin",
   "parent": "hrm:goal/scarless-skin-repair",
   "description": "Rebuild every layer and structure: epidermis, dermis, organised microvasculature, appendages (follicles, glands), innervation, pigmentation. Each is a capability that can fail independently.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "requires": [
    {
     "any": [
      "hrm:capability/epidermis-replacement-cultured-autograft",
      "hrm:capability/epidermis-gene-corrected-stem-cell-replacement",
      "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery"
     ],
     "note": "Epidermal restoration: any of three demonstrated routes, chosen by cause."
    },
    {
     "all": [
      "hrm:capability/dermal-architecture-regeneration-without-scar",
      "hrm:capability/native-ecm-organisation-reconstruction",
      "hrm:capability/organised-microvascular-network-in-regenerated-dermis",
      "hrm:capability/cutaneous-sensory-reinnervation",
      "hrm:capability/hair-follicle-neogenesis-after-wounding",
      "hrm:capability/dermal-adipocyte-regeneration",
      "hrm:capability/melanocyte--edit"
     ]
    },
    {
     "any": [
      "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
      "hrm:capability/hair-follicle-neogenesis-after-wounding"
     ],
     "note": "Appendages: regenerate in place OR graft an appendage-bearing construct."
    }
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/scarless-skin-repair"
    ]
   }
  },
  {
   "type": "goal",
   "id": "hrm:goal/systemic-rejuvenation",
   "name": "Systemic rejuvenation",
   "parent": "hrm:goal/rejuvenation",
   "description": "Rejuvenate many tissues of one person at once, safely and durably. Decomposes, per the owner's brief, into a safe rejuvenation mechanism AND multi-tissue delivery AND cancer control — with the delivery leg satisfiable by more than one route.",
   "projections": [
    "rejuvenation"
   ],
   "requires": [
    {
     "all": [
      "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
      "hrm:capability/cell-identity-retention-under-partial-reprogramming",
      "hrm:capability/cancer-risk-control-under-rejuvenation",
      "hrm:capability/rejuvenated-state-persistence"
     ]
    },
    {
     "any": [
      "hrm:capability/systemic-cell-type-specific-delivery",
      "hrm:capability/cns-neuron--reach"
     ],
     "note": "OR-group: one delivery route sufficing for the tissue in question; nobody knows which will succeed. cns-neuron--reach is the v0.2 grid cell backed by the 16 CNS routes."
    }
   ],
   "blockedBy": [
    "hrm:question/cancer-risk-of-repeated-partial-reprogramming",
    "hrm:question/healthy-target-state-for-aged-tissue",
    "hrm:question/partial-reprogramming-human-safety",
    "hrm:question/rejuvenated-state-persistence-and-redosing",
    "hrm:question/rejuvenation-reach-beyond-eye-and-liver"
   ],
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "enables": [
     "hrm:goal/rejuvenation"
    ],
    "blockedBy": [
     "hrm:question/partial-reprogramming-human-safety",
     "hrm:question/rejuvenation-reach-beyond-eye-and-liver",
     "hrm:question/rejuvenated-state-persistence-and-redosing",
     "hrm:question/cancer-risk-of-repeated-partial-reprogramming",
     "hrm:question/healthy-target-state-for-aged-tissue"
    ]
   }
  },
  {
   "type": "goal",
   "id": "hrm:goal/universal-repair",
   "name": "Universal repair",
   "description": "Restore a person from arbitrary biological damage — trauma, infection, cancer, genetic disease, autoimmunity, organ failure, neurological injury — to their healthy functional state, preserving who they are. The root of the Universal Repair projection. Rejuvenation is a specialised branch of it, not a separate universe.",
   "projections": [
    "universal-repair"
   ],
   "requires": [
    {
     "all": [
      "hrm:goal/scarless-skin-repair",
      "hrm:goal/established-scar-repair"
     ],
     "note": "First proving ground only. Peripheral nerve, fracture, myocardium, sepsis, cancer and systemic rejuvenation are the planned expansions and are not yet nodes."
    }
   ],
   "testSuite": [
    {
     "scenario": "small skin wound",
     "state": "routine"
    },
    {
     "scenario": "superficial infection",
     "state": "routine"
    },
    {
     "scenario": "severe laceration with full function restored",
     "state": "partial"
    },
    {
     "scenario": "compound fracture",
     "state": "partial"
    },
    {
     "scenario": "internal haemorrhage",
     "state": "partial"
    },
    {
     "scenario": "myocardial infarction with muscle restored",
     "state": "unsolved"
    },
    {
     "scenario": "sepsis",
     "state": "partial"
    },
    {
     "scenario": "spinal cord transection",
     "state": "unsolved"
    },
    {
     "scenario": "metastatic cancer",
     "state": "unsolved"
    },
    {
     "scenario": "systemic aging",
     "state": "unsolved"
    }
   ],
   "informationLimited": false,
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "children": [
     "hrm:goal/established-scar-repair",
     "hrm:goal/scarless-skin-repair"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/cancer-risk-of-repeated-partial-reprogramming",
   "projections": [
    "rejuvenation"
   ],
   "question": "What is the cancer risk of repeated partial reprogramming in aged human tissue, and can it be bounded by a stopping rule?",
   "why": "Rejuvenation and oncogenesis share machinery. Nobody will accept a rejuvenation treatment in healthy people without an answer, and the answer is only observable over years.",
   "blocks": [
    "hrm:capability/cancer-risk-control-under-rejuvenation",
    "hrm:goal/systemic-rejuvenation"
   ],
   "knownUnknowns": [
    "dose–response for transformation",
    "interaction with pre-existing clonal expansions in aged tissue",
    "whether a biomarker of proliferative drift exists"
   ],
   "whatWouldResolve": "Long-term cancer incidence in treated versus untreated aged animals and, eventually, humans; and a validated early biomarker of transformation risk.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:goal/systemic-rejuvenation",
     "hrm:capability/cancer-risk-control-under-rejuvenation"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/dermal-adipocyte-regeneration-in-human-wounds",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "question": "Can dermal adipocyte regeneration from myofibroblasts be induced in human wounds?",
   "why": "Loss of the dermal fat layer is part of what makes scar stiff and depressed; mouse shows it can be regenerated.",
   "blocks": [
    "hrm:capability/dermal-adipocyte-regeneration"
   ],
   "whatWouldResolve": "Adipocyte lineage conversion demonstrated in human wound tissue or xenograft.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:capability/dermal-adipocyte-regeneration"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/en1-inhibition-translates-to-human-skin",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "question": "Does blocking Engrailed-1 activation (mechanotransduction/YAP inhibition) produce regeneration with appendages and native matrix in porcine or human skin, as it does in mouse?",
   "why": "It is the only demonstrated route to scarless full-thickness regeneration in an adult mammal that is also a drug (verteporfin is approved for another use). If it translates, four capabilities move from L2 toward L3/L4 at once; if it does not, the mouse result is a mechanism, not a therapy.",
   "blocks": [
    "hrm:capability/dermal-architecture-regeneration-without-scar",
    "hrm:capability/fibrogenic-fibroblast-lineage-control",
    "hrm:capability/native-ecm-organisation-reconstruction",
    "hrm:goal/scarless-skin-repair"
   ],
   "hypotheses": [
    "The mechanism is conserved and translates with dose adjustment.",
    "Human skin's tension, thickness and slower healing make the fibrotic lineage dominant regardless of YAP inhibition.",
    "Regeneration occurs but appendage neogenesis does not, because human wounds lack the Wnt context of mouse large wounds."
   ],
   "knownUnknowns": [
    "dose and timing window in thick skin",
    "whether human fibroblast subpopulations map onto the mouse Engrailed-1 lineage",
    "effect on wound closure speed and tensile strength"
   ],
   "whatWouldResolve": "A splinted full-thickness wound study in pig skin, or a human scar-revision trial, with appendage counts and matrix ultrastructure as endpoints, from a group unaffiliated with the original.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:goal/scarless-skin-repair",
     "hrm:capability/dermal-architecture-regeneration-without-scar",
     "hrm:capability/fibrogenic-fibroblast-lineage-control",
     "hrm:capability/native-ecm-organisation-reconstruction"
    ],
    "testedBy": [
     "hrm:experiment/verteporfin-porcine-full-thickness-wound"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/established-scar-remodelling-to-native-architecture",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "question": "Can a mature dermal scar be remodelled into dermis with native matrix organisation and appendages?",
   "why": "Prevention helps the next wound; reversal helps everyone already scarred, and every fibrotic organ shares the problem.",
   "blocks": [
    "hrm:capability/established-dermal-scar-reversal",
    "hrm:goal/established-scar-repair"
   ],
   "hypotheses": [
    "Scar matrix can be degraded and replaced if the fibroblasts are reprogrammed.",
    "Mature cross-linked matrix cannot be remodelled to native architecture without excision."
   ],
   "whatWouldResolve": "Histological conversion of an established scar to basket-weave dermis with appendages in any adult mammal.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:goal/established-scar-repair",
     "hrm:capability/established-dermal-scar-reversal"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/fetal-conditions-reproducible-in-adult-skin",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "question": "Which features of early-gestation fetal wound healing are causal for scarlessness, and can they be reproduced in adult skin?",
   "why": "The fetal state is the only human state known to heal without scar. If its causal features can be imposed on adult wounds, scarless repair becomes an adult capability.",
   "blocks": [
    "hrm:capability/fetal-scarless-healing-target-state"
   ],
   "whatWouldResolve": "An adult-skin wound that heals without scar after imposing a defined subset of fetal conditions (inflammation, growth-factor profile, matrix).",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:capability/fetal-scarless-healing-target-state"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/gene-corrected-epidermal-graft-long-term-safety",
   "projections": [
    "universal-repair"
   ],
   "question": "Do gene-corrected epidermal stem-cell grafts remain stable and free of clonal or malignant events beyond five years?",
   "why": "Retroviral integration in long-lived stem cells is the safety question that decides whether the approach can be offered widely.",
   "blocks": [
    "hrm:capability/epidermis-gene-corrected-stem-cell-replacement"
   ],
   "whatWouldResolve": "Integration-site analysis and clinical follow-up beyond five years in the treated patients, published.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:capability/epidermis-gene-corrected-stem-cell-replacement"
    ],
    "testedBy": [
     "hrm:experiment/gene-corrected-epidermal-graft-long-term-registry"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/healthy-target-state-for-aged-tissue",
   "projections": [
    "rejuvenation"
   ],
   "question": "What counts as the healthy target state for an aged person's tissue — youthful architecture, age-appropriate function, or something the person defines?",
   "why": "Target-state content is human-gated on this map (ai-collaboration.md §4). The question is recorded so the dependency is visible; it is not for a model to resolve.",
   "blocks": [
    "hrm:goal/rejuvenation",
    "hrm:goal/systemic-rejuvenation"
   ],
   "hypotheses": [
    "A population reference state at a younger age.",
    "The person's own earlier state, where records exist.",
    "A personalised optimum co-defined with the person, including what must not change."
   ],
   "whatWouldResolve": "A published, reviewed target-state framework adopted by a rejuvenation trial as its endpoint definition.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:goal/systemic-rejuvenation",
     "hrm:goal/rejuvenation"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/nondestructive-fibroblast-state-readout-in-human-wounds",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "question": "Can fibroblast state (fibrotic versus regenerative trajectory) be read non-destructively in a living human wound early enough to intervene?",
   "why": "Without a readout there is no closed loop: every anti-fibrotic intervention is dosed blind and verified only by the scar.",
   "blocks": [
    "hrm:capability/fibroblast-state-sensing-in-living-wound"
   ],
   "whatWouldResolve": "A non-invasive measurement in human wounds that predicts scar outcome at 12 months.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:capability/fibroblast-state-sensing-in-living-wound"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/organised-microvasculature-in-thick-regenerated-tissue",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "question": "Can an organised, hierarchical, perfused microvascular network be induced throughout regenerated or engineered dermis thicker than the diffusion limit, in humans, with normal geometry and long-term stability?",
   "why": "Without it, any regenerated tissue thicker than a few hundred micrometres dies in the middle. It gates dermal regeneration, engineered grafts and every thick-tissue repair on the universal map.",
   "blocks": [
    "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
    "hrm:capability/organised-microvascular-network-in-regenerated-dermis"
   ],
   "hypotheses": [
    "Prevascularised constructs anastomose fast enough if the network is pre-patterned.",
    "Host angiogenesis can be driven to hierarchy by controlled growth-factor gradients.",
    "Only surgical microvascular connection (flaps) will work at clinical scale."
   ],
   "whatWouldResolve": "A thick (>2 mm) regenerated or engineered dermis in a large animal or human with perfusion measured throughout at six months and vessel hierarchy on histology.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:capability/organised-microvascular-network-in-regenerated-dermis",
     "hrm:capability/appendage-bearing-skin-from-pluripotent-cells"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/partial-reprogramming-human-safety",
   "projections": [
    "rejuvenation"
   ],
   "question": "Can partial epigenetic reprogramming rejuvenate a human tissue without dedifferentiation, loss of cell identity or tumour formation?",
   "why": "It is the first rejuvenation mechanism to reach a human; its safety window decides whether the rejuvenation map has a therapeutic root at all.",
   "blocks": [
    "hrm:capability/cell-identity-retention-under-partial-reprogramming",
    "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
    "hrm:goal/systemic-rejuvenation"
   ],
   "hypotheses": [
    "A controlled expression window exists in humans as it does in mice.",
    "Human cells require longer exposure for effect, which overlaps the dedifferentiation window."
   ],
   "knownUnknowns": [
    "safe expression window",
    "delivery efficiency to the target cells",
    "long-term epigenetic stability"
   ],
   "whatWouldResolve": "Phase 1 safety data plus any functional signal from the first OSK trial (NCT07290244), then a functional endpoint in a controlled study.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:goal/systemic-rejuvenation",
     "hrm:capability/cell-identity-retention-under-partial-reprogramming",
     "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo"
    ],
    "testedBy": [
     "hrm:experiment/er-100-phase-1-optic-neuropathies"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/pluripotent-derived-skin-engrafts-in-humans",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "question": "Can pluripotent-stem-cell-derived, appendage-bearing skin engraft in a human, vascularise, and remain stable?",
   "why": "It is the alternative to regenerating appendages in place, and the only current route to human skin with follicles built outside the body.",
   "blocks": [
    "hrm:capability/appendage-bearing-skin-from-pluripotent-cells"
   ],
   "whatWouldResolve": "A first-in-human graft with survival, vascularisation and appendage persistence at one year.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:capability/appendage-bearing-skin-from-pluripotent-cells"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/regenerated-skin-sensory-reinnervation",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "question": "Does regenerated or grafted skin regain sensory innervation comparable to uninjured skin, and what limits it?",
   "why": "Skin without sensation is injured skin. Reinnervation is required for function and is rarely measured as an endpoint.",
   "blocks": [
    "hrm:capability/cutaneous-sensory-reinnervation"
   ],
   "whatWouldResolve": "Quantitative sensory testing plus nerve-fibre density on biopsy in regenerated versus uninjured skin at one year.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:capability/cutaneous-sensory-reinnervation"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/rejuvenated-state-persistence-and-redosing",
   "projections": [
    "rejuvenation"
   ],
   "question": "Does a rejuvenated state persist after treatment stops, and can treatment be repeated without cumulative harm?",
   "why": "A rejuvenation that lasts a month is a treatment; one that lasts a decade is the goal. The verification to tell them apart does not yet exist in humans.",
   "blocks": [
    "hrm:capability/rejuvenated-state-persistence",
    "hrm:goal/systemic-rejuvenation"
   ],
   "whatWouldResolve": "Longitudinal epigenetic-age and functional measurement in a treated human tissue over years, with and without re-dosing.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:goal/systemic-rejuvenation",
     "hrm:capability/rejuvenated-state-persistence"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/rejuvenation-reach-beyond-eye-and-liver",
   "projections": [
    "rejuvenation"
   ],
   "question": "Can a rejuvenation payload reach tissues beyond the eye and liver — heart, brain, muscle — at useful efficiency?",
   "why": "Systemic rejuvenation is gated by delivery. The eye is chosen first because it is reachable; the tissues that matter for lifespan are not.",
   "blocks": [
    "hrm:capability/systemic-cell-type-specific-delivery",
    "hrm:goal/systemic-rejuvenation"
   ],
   "whatWouldResolve": "Cell-type-specific transduction quantified in a non-ocular human tissue from a systemic dose, by any group.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:goal/systemic-rejuvenation",
     "hrm:capability/systemic-cell-type-specific-delivery"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/reliable-biofilm-eradication-in-chronic-wounds",
   "projections": [
    "universal-repair"
   ],
   "question": "Can established polymicrobial biofilm be reliably eradicated from chronic human wounds?",
   "why": "Biofilm is the commonest reason a wound that could heal does not; the map has no grade for the capability because the seed did not search it.",
   "blocks": [
    "hrm:capability/chronic-wound-biofilm-eradication",
    "hrm:goal/skin-contamination-control"
   ],
   "whatWouldResolve": "A randomised trial with microbiologically confirmed eradication and closure as endpoints.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:goal/skin-contamination-control",
     "hrm:capability/chronic-wound-biofilm-eradication"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/skin-substitutes-improve-scar-quality-not-just-closure",
   "projections": [
    "universal-repair"
   ],
   "question": "Do bioengineered skin substitutes improve the quality of the healed skin (scar scale, appendages, sensation) rather than only the rate of closure?",
   "why": "Closure is the endpoint that got them approved; quality is what regeneration means. The trials on this map did not measure it.",
   "blocks": [
    "hrm:capability/dermal-substitute-for-chronic-wound-closure"
   ],
   "whatWouldResolve": "A randomised trial with a validated scar-quality primary endpoint at 12 months.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:capability/dermal-substitute-for-chronic-wound-closure"
    ],
    "testedBy": [
     "hrm:experiment/skin-substitute-scar-quality-rct"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/topical-gene-delivery-generalises-beyond-eb",
   "projections": [
    "universal-repair"
   ],
   "question": "Does topical HSV-vector gene delivery to keratinocytes generalise to other genes and non-EB indications, and by unaffiliated groups?",
   "why": "One approved product proves the route; generality is what makes it a capability rather than a product.",
   "blocks": [
    "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery"
   ],
   "whatWouldResolve": "Durable expression of a second gene in a second indication in a randomised trial not run by the original sponsor.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/what-limits-regeneration-in-mus-and-human",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "question": "What, mechanistically, stops laboratory mice and humans from regenerating skin the way spiny mice do — the immune response, the matrix, the fibroblast lineage, or something else?",
   "why": "The existence proof says the capability is within mammalian reach; the discriminating comparison says where to intervene. Every biological-control capability on this map depends on the answer.",
   "blocks": [
    "hrm:capability/fibrogenic-fibroblast-lineage-control",
    "hrm:capability/inflammation-phase-control-for-regeneration",
    "hrm:capability/mammalian-scar-free-regeneration-target-state",
    "hrm:goal/scarless-skin-repair",
    "hrm:goal/skin-biological-control"
   ],
   "hypotheses": [
    "A muted or differently timed inflammatory response permits regeneration.",
    "A different composition of the provisional matrix (less collagen I, more collagen III/tenascin) permits it.",
    "Acomys lacks or suppresses a fibrogenic fibroblast lineage.",
    "Several of these, and they are coupled."
   ],
   "whatWouldResolve": "Matched single-cell and spatial atlases of Acomys versus Mus wounds at the same timepoints, with lineage tracing, and a perturbation that converts one phenotype toward the other.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:goal/scarless-skin-repair",
     "hrm:goal/skin-biological-control",
     "hrm:capability/fibrogenic-fibroblast-lineage-control",
     "hrm:capability/inflammation-phase-control-for-regeneration",
     "hrm:capability/mammalian-scar-free-regeneration-target-state"
    ],
    "testedBy": [
     "hrm:experiment/acomys-vs-mus-matched-wound-atlas"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/why-avotermin-phase-3-failed",
   "projections": [
    "universal-repair"
   ],
   "question": "Why did avotermin (TGF-β3) fail in phase 3 after positive double-blind phase I/II and phase II results — and where are the phase 3 data?",
   "why": "It is the best-documented human anti-scarring effect ever published and it did not survive its confirmatory trial. Until the failure is understood, every pharmacological scar-reduction claim inherits the uncertainty.",
   "blocks": [
    "hrm:capability/pharmacological-scar-reduction-in-humans",
    "hrm:goal/skin-biological-control"
   ],
   "hypotheses": [
    "The phase I/II effect was real but small and endpoint-sensitive; phase 3 used a different scar-assessment endpoint.",
    "Dose or timing differed between phases.",
    "The earlier effect was partly an artefact of within-participant design."
   ],
   "knownUnknowns": [
    "the phase 3 protocol and endpoints",
    "whether the data were ever released"
   ],
   "whatWouldResolve": "Publication or release of the phase 3 dataset (registered trials: NCT00847925, NCT00847795, NCT00629811 were the phase I/II).",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:goal/skin-biological-control",
     "hrm:capability/pharmacological-scar-reduction-in-humans"
    ]
   }
  },
  {
   "type": "question",
   "state": "open",
   "id": "hrm:question/wound-induced-hair-neogenesis-in-human-skin",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "question": "Can de novo hair follicle neogenesis occur in adult human wounds, or is it lost with development?",
   "why": "Appendage regeneration is the visible difference between regeneration and scar. Mouse large wounds do it; if human skin cannot, appendages must come from a graft instead.",
   "blocks": [
    "hrm:capability/hair-follicle-neogenesis-after-wounding"
   ],
   "hypotheses": [
    "Human skin retains the competence and lacks the trigger (wound size, Wnt).",
    "Competence is lost postnatally in humans."
   ],
   "whatWouldResolve": "Documented follicle neogenesis, distinguished from survival of pre-existing follicles, in a large adult human wound or a human skin xenograft.",
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "manual reasoning from the cited sources' abstracts (PubMed) and Crossref metadata, checked 2026-09-11; no source opened at figure level",
    "date": "2026-09-11"
   },
   "review": {
    "state": "ai-proposed",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "blocks": [
     "hrm:capability/hair-follicle-neogenesis-after-wounding"
    ],
    "testedBy": [
     "hrm:experiment/wihn-human-xenograft-large-wound"
    ]
   }
  },
  {
   "id": "hrm:route/aav9",
   "type": "route",
   "name": "Systemic AAV9, IV (onasemnogene abeparvovec / Zolgensma)",
   "family": "through barrier",
   "rung": "L4",
   "grounding": "G1",
   "measured": "function",
   "score": 52,
   "status": "approved 2019 (FDA)",
   "replication": "none for CNS transduction — single sponsor-affiliated n=2 autopsy",
   "note": "Clinical benefit in SMA is real and replicated. Direct human CNS transduction rests on two deceased infants, with liver vector 300–1000x higher than CNS.",
   "drift": "\"Proves IV AAV9 transduces human CNS\" rests on two autopsies; clinical benefit is offered as transduction evidence, but it is not.",
   "citations": [
    "Thomsen et al., Nat Med, 2021"
   ],
   "wouldMove": "An independent human biodistribution study with single-cell quantification of the transduced neuronal fraction.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/bihtfr1",
   "type": "route",
   "name": "Human-TfR-targeted capsid (BI-hTFR1)",
   "family": "through barrier",
   "rung": "L2",
   "grounding": "G1",
   "measured": "none",
   "score": 16,
   "status": "preclinical",
   "replication": "none located",
   "note": "Works in humanised-TfR knock-in mice and human brain endothelial cells. Cannot be tested in wild-type primates.",
   "drift": "A promising engineering answer to the LY6A problem, with zero human data.",
   "citations": [
    "Huang et al., Science, 2024"
   ],
   "wouldMove": "Any first-in-human dosing with biodistribution data; or independent replication in a humanised primate model.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/brineura",
   "type": "route",
   "name": "ICV enzyme replacement (cerliponase alfa / Brineura)",
   "family": "around barrier",
   "rung": "L4",
   "grounding": "G2",
   "measured": "function",
   "score": 58,
   "status": "approved 2017 (FDA)",
   "replication": "NOT independent — both studies share a senior author (Schulz, Hamburg)",
   "note": "Shown to slow the brain disease. Rung lowered 2026-07-27: the two supporting studies share a senior author, so the independent-replication claim does not hold. The children's retinas degenerate on schedule, untouched — the enzyme poured into the centre of the brain never reaches them.",
   "drift": "\"ICV distributes enzyme through the brain\" — the retinal finding is the cleanest human proof of incomplete reach.",
   "citations": [
    "Lancet Neurol, 2023 (open-label extension)",
    "Front Neurol, 2025 (real-world)"
   ],
   "wouldMove": "Evidence of enzyme reaching distal/ocular compartments would extend the distribution claim.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "disputed"
   }
  },
  {
   "id": "hrm:route/capsid",
   "type": "route",
   "name": "Engineered AAV capsid, IV (PHP.B family)",
   "family": "through barrier",
   "rung": "L2",
   "grounding": "G1",
   "measured": "none",
   "score": 18,
   "status": "terminated",
   "replication": "independent in mice; independently FAILED in primates (three unaffiliated groups)",
   "note": "~10,000x better mouse-brain delivery than AAV9 — through the LY6A receptor, which humans do not have. Failed primate IV transduction in three independent studies; next-generation capsids failed an independent 2025 marmoset re-test. Exactly one human was ever IV-dosed an engineered BBB capsid (Capsida CAP-002); that patient died, the trial was terminated, and the sister programme was withdrawn without dosing.",
   "drift": "\"A virus that crosses the blood-brain barrier\" — via a receptor humans lack, failed in every independent primate test, with one human exposure that ended in death.",
   "precision": "The Capsida trial pause was the company's own. No public document establishes the later regulatory hold as FDA-imposed; do not state that it was.",
   "citations": [
    "Deverman et al., Nat Biotechnol, 2016",
    "Hordeaux et al., Mol Ther, 2018/2019",
    "Liguore et al., Mol Ther, 2019",
    "Capsida community letter, 2026"
   ],
   "wouldMove": "A human-compatible receptor mechanism demonstrated in primates by an unaffiliated group.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "disputed"
   }
  },
  {
   "id": "hrm:route/cart",
   "type": "route",
   "name": "Locoregional CAR-T (intraventricular / intracavitary)",
   "family": "around barrier",
   "rung": "L5",
   "grounding": "G1",
   "measured": "function",
   "score": 62,
   "status": "in trials",
   "replication": "independent — four unaffiliated centres",
   "note": "The strongest functional responses on the map, for childhood brainstem tumours and glioblastoma, delivered into the ventricles or tumour cavity.",
   "drift": "\"CAR-T reaches brain tumours\" omits that every responding programme injects into the ventricle or cavity; IV dosing produced the dose-limiting toxicity, not the responses.",
   "citations": [
    "Monje et al., Nature, 2025",
    "Brown et al., Nat Med, 2024",
    "Vitanza et al., Nat Med, 2025"
   ],
   "wouldMove": "An independent group replicating target-specific efficacy (not just the route) would move this from route-replicated to efficacy-replicated.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/ced",
   "type": "route",
   "name": "Convection-enhanced delivery (catheter under pressure)",
   "family": "around barrier",
   "rung": "L4",
   "grounding": "G2",
   "measured": "none",
   "score": 24,
   "status": "trials failed",
   "replication": "no replicated positive outcome; two powered trials negative",
   "note": "Decades of human use. The powered brain-cancer trial (PRECISE) and the powered Parkinson's GDNF trial both missed their endpoints. A blinded audit found roughly half the PRECISE catheters misplaced — the study may have tested a drug it never delivered.",
   "drift": "\"CED bypasses the BBB and delivers to the target\" — bypass is real; verified coverage is the unsolved problem.",
   "citations": [
    "Kunwar et al. (PRECISE), Neuro-Oncology, 2010",
    "Whone et al., Brain, 2019",
    "Sampson et al., J Neurosurg, 2010"
   ],
   "wouldMove": "A trial with real-time imaging confirmation of target coverage that then meets a clinical endpoint.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "disputed"
   }
  },
  {
   "id": "hrm:route/denali",
   "type": "route",
   "name": "TfR receptor-mediated transcytosis (tividenofusp alfa)",
   "family": "through barrier",
   "rung": "L4",
   "grounding": "G2",
   "measured": "biomarker",
   "score": 48,
   "status": "approved 2026-03-25 (FDA, accelerated)",
   "replication": "none (concept cross-confirmed by an unaffiliated TfR construct)",
   "note": "First BBB-crossing biologic approved. Rests on a 91% drop in CSF heparan sulfate, a surrogate. The confirmatory cognitive trial (COMPASS) is still running. No human measurement of enzyme in brain parenchyma.",
   "drift": "\"A drug that crosses the BBB and treats neurologic Hunter syndrome\" — what was shown is a CSF sugar falling, with no proven cognitive benefit.",
   "citations": [
    "FDA approval, 2026",
    "Phase 1/2, NEJM, 2026"
   ],
   "wouldMove": "COMPASS reading out a cognitive/functional benefit would convert the surrogate into demonstrated function.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/exosomes",
   "type": "route",
   "name": "Engineered exosomes / extracellular vesicles",
   "family": "through barrier",
   "rung": "L2",
   "grounding": "G1",
   "measured": "none",
   "score": 14,
   "status": "preclinical",
   "replication": "none — primate study found EVs in CSF but minimal brain parenchymal accumulation",
   "note": "Rodent evidence, a negative primate result, no approvals, and a registry-only clinical footprint. FDA has issued a safety notification on unapproved exosome products.",
   "drift": "A preclinical platform presented as clinical-stage.",
   "citations": [
    "Alvarez-Erviti et al., Nat Biotechnol, 2011",
    "Driedonks et al., J Extracell Biol, 2022"
   ],
   "wouldMove": "A positive, independently replicated primate biodistribution study.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/fus",
   "type": "route",
   "name": "Focused ultrasound + microbubbles (BBB opening)",
   "family": "around barrier",
   "rung": "L5",
   "grounding": "G1",
   "measured": "opening",
   "score": 56,
   "status": "in trials",
   "replication": "independent — at least six unaffiliated groups",
   "note": "Reversible, repeatable, safe BBB opening is proven in humans. Whether a drug pushed through the opening improves an outcome has not been shown in a randomised trial.",
   "drift": "\"FUS delivers drugs and extends survival\" — the opening is proven; the outcome trial does not yet exist.",
   "citations": [
    "Lipsman et al., Nat Commun, 2018",
    "Woodworth/Lipsman et al., Lancet Oncol, 2025"
   ],
   "wouldMove": "A positive randomised outcome trial (SONOBIRD, n=560, reports ~end-2026) would convert this from proven-opening to proven-delivery.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/intranasal",
   "type": "route",
   "name": "Intranasal / nose-to-brain",
   "family": "through barrier",
   "rung": "L4",
   "grounding": "G1",
   "measured": "biomarker",
   "score": 30,
   "status": "in trials",
   "replication": "contested — strongest independent human attempt was negative",
   "note": "The theory is mostly rodent-inferred. The large human functional test — intranasal insulin for Alzheimer's (SNIFF, n=289) — was null (P=.98). Esketamine works by ordinary systemic absorption and is not nose-to-brain evidence.",
   "drift": "\"Bypasses the BBB via olfactory pathways\" — human data support only trace, highly variable CSF appearance, not meaningful parenchymal concentration.",
   "citations": [
    "Craft et al. (SNIFF), JAMA Neurol, 2020",
    "Winterdahl et al., EJNMMI Res, 2025"
   ],
   "wouldMove": "Quantitative human evidence of therapeutic parenchymal concentration, plus a positive functional trial.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/jcr",
   "type": "route",
   "name": "TfR fusion (pabinafusp alfa / Izcargo)",
   "family": "through barrier",
   "rung": "L4",
   "grounding": "G2",
   "measured": "biomarker",
   "score": 42,
   "status": "approved 2021 (Japan only)",
   "replication": "none",
   "note": "n=28, CSF heparan sulfate reduction. Cognitive improvement is claimed only in a post-hoc, open-label subgroup treated before significant neuronopathy.",
   "drift": "An approval on a priority pathway with n=28 and a biomarker co-primary, read as proof that RMT delivers to human brain.",
   "citations": [
    "Okuyama et al., Mol Ther, 2021"
   ],
   "wouldMove": "A randomised controlled trial with a functional endpoint, and approval outside Japan.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/kebilidi",
   "type": "route",
   "name": "Direct intraparenchymal gene therapy (eladocagene / Kebilidi / Upstaza)",
   "family": "around barrier",
   "rung": "L4",
   "grounding": "G2",
   "measured": "function",
   "score": 50,
   "status": "approved EU 2022 / FDA 2024",
   "replication": "route replicated (different product, unaffiliated group)",
   "note": "First gene therapy administered directly into brain tissue in the US. A virus infused into one deep structure, the putamen: precise, single-shot, essentially zero distal distribution.",
   "drift": "Viable only for rare diseases whose whole problem sits in one anatomically defined place.",
   "citations": [
    "Tai et al., Mol Ther, 2022",
    "Pearson/Bankiewicz et al., Nat Commun, 2021"
   ],
   "wouldMove": "An unaffiliated group replicating this product's outcome would lift it from single-group to independent.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/lnp",
   "type": "route",
   "name": "Lipid nanoparticles to brain, systemic",
   "family": "through barrier",
   "rung": "L2",
   "grounding": "G1",
   "measured": "none",
   "score": 20,
   "status": "preclinical",
   "replication": "independent (rodent only)",
   "note": "Rodent only. No human data and no registered human trial for brain delivery. The one human GBM LNP trial (n=3) works via peripheral immune signalling, not BBB crossing.",
   "drift": "\"LNPs can now cross the BBB\" describes reporter mRNA in mouse brain.",
   "citations": [
    "Wang et al., Nat Mater, 2025",
    "Sayour et al., Cell, 2024"
   ],
   "wouldMove": "A non-human-primate systemic study showing brain parenchymal delivery, then first-in-human.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/nusinersen",
   "type": "route",
   "name": "Intrathecal ASO (nusinersen / Spinraza)",
   "family": "around barrier",
   "rung": "L5",
   "grounding": "G2",
   "measured": "function",
   "score": 70,
   "status": "approved 2016 (FDA)",
   "replication": "independent",
   "note": "Real, independently replicated improvement in children's motor milestones. Human autopsy shows a steep caudo-rostral gradient: plenty in the lumbar spine, little by the cortex.",
   "drift": "Cited as proof of CNS-wide ASO delivery; the disease treated sits in the spinal cord, and human tissue shows a spinal-weighted gradient.",
   "citations": [
    "Ramos et al., J Clin Invest, 2019 (autopsy)"
   ],
   "wouldMove": "Human evidence of therapeutic concentration in deep brain nuclei would extend this claim from spinal cord to brain.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/roche",
   "type": "route",
   "name": "Brainshuttle antibody (trontinemab)",
   "family": "through barrier",
   "rung": "L4",
   "grounding": "G1",
   "measured": "biomarker",
   "score": 40,
   "status": "Phase 3, not approved",
   "replication": "none — all sponsor-generated",
   "note": "Clears amyloid plaque on PET at low ARIA. The only direct human exposure number is a CSF:plasma ratio of 0.8%, and CSF is a poor proxy for parenchyma.",
   "drift": "\"Brainshuttle validated\" — the 10–50x brain-uptake figure is a mouse/NHP number; the human data are one CSF ratio and a plaque-clearance response.",
   "citations": [
    "Klein et al., Alzheimers Dement, 2025",
    "Grimm et al., mAbs, 2023"
   ],
   "wouldMove": "TRONTIER Phase 3 showing slowed cognitive decline; or direct human parenchymal measurement (PET/autopsy).",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:route/tofersen",
   "type": "route",
   "name": "Intrathecal ASO (tofersen / Qalsody)",
   "family": "around barrier",
   "rung": "L4",
   "grounding": "G2",
   "measured": "biomarker",
   "score": 44,
   "status": "approved 2023 (FDA, accelerated)",
   "replication": "none",
   "note": "Approved on plasma neurofilament light, a surrogate. The Phase 3 VALOR trial missed its clinical endpoint.",
   "drift": "\"ASOs work in ALS\" — what was shown is biomarker engagement without a met clinical endpoint.",
   "citations": [
    "Biogen/FDA, 2023"
   ],
   "wouldMove": "The confirmatory ATLAS trial showing a functional benefit would convert a surrogate approval into demonstrated function.",
   "projections": [
    "universal-repair",
    "rejuvenation"
   ],
   "supports": [
    "hrm:capability/cns-neuron--reach"
   ],
   "review": {
    "state": "ai-proposed"
   }
  },
  {
   "id": "hrm:source/blais-2013-tissueeng",
   "type": "source",
   "citation": "Blais et al., Tissue Engineering Part A, 2013",
   "title": "Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3 and Glial-Derived Neurotrophic Factor Enhance Angiogenesis in a Tissue-Engineered In Vitro Model",
   "authors": "Blais Mathieu; Lévesque Philippe; Bellenfant Sabrina; Berthod François",
   "venue": "Tissue Engineering Part A",
   "year": 2013,
   "kind": "article",
   "doi": "10.1089/ten.tea.2012.0745",
   "pmid": "23530859",
   "url": "https://doi.org/10.1089/ten.tea.2012.0745",
   "license": "https://www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/",
   "resolution": {
    "resolved": true,
    "checkedOn": "2026-09-11",
    "via": "crossref",
    "metadataMatches": true,
    "resolvedTitle": "Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3 and Glial-Derived Neurotrophic Factor Enhance Angiogenesis in a Tissue-Engineered In Vitro Model",
    "note": "Crossref record found; PubMed id 23530859 located by DOI."
   },
   "provenance": {
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     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
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    "method": "source record generated from the live Crossref work record and a PubMed id lookup by DOI (scripts/seed/2026-09-11-scarless-skin.mjs)",
    "date": "2026-09-11"
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   "id": "hrm:source/brant-2016-wrr",
   "type": "source",
   "citation": "Brant et al., Wound Repair and Regeneration, 2016",
   "title": "Cellular events during scar‐free skin regeneration in the spiny mouse, Acomys",
   "authors": "Brant Jason O.; Yoon Jung H.; Polvadore Trey; Barbazuk William Brad; Maden Malcolm",
   "venue": "Wound Repair and Regeneration",
   "year": 2016,
   "kind": "article",
   "doi": "10.1111/wrr.12385",
   "pmid": "26606280",
   "url": "https://doi.org/10.1111/wrr.12385",
   "license": "http://onlinelibrary.wiley.com/termsAndConditions#vor",
   "resolution": {
    "resolved": true,
    "checkedOn": "2026-09-11",
    "via": "crossref",
    "metadataMatches": true,
    "resolvedTitle": "Cellular events during scar‐free skin regeneration in the spiny mouse, Acomys",
    "note": "Crossref record found; PubMed id 26606280 located by DOI."
   },
   "provenance": {
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     "name": "Claude Code session e7dc5601 (Anthropic)",
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    "method": "source record generated from the live Crossref work record and a PubMed id lookup by DOI (scripts/seed/2026-09-11-scarless-skin.mjs)",
    "date": "2026-09-11"
   },
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  },
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   "id": "hrm:source/chan-2015-scitranslmed",
   "type": "source",
   "citation": "Chan et al., Science Translational Medicine, 2015",
   "title": "A synthetic fibrin cross-linking polymer for modulating clot properties and inducing hemostasis",
   "authors": "Chan Leslie W.; Wang Xu; Wei Hua; Pozzo Lilo D.; White Nathan J.; Pun Suzie H.",
   "venue": "Science Translational Medicine",
   "year": 2015,
   "kind": "article",
   "doi": "10.1126/scitranslmed.3010383",
   "pmid": "25739763",
   "url": "https://doi.org/10.1126/scitranslmed.3010383",
   "license": "http://www.sciencemag.org/about/science-licenses-journal-article-reuse",
   "resolution": {
    "resolved": true,
    "checkedOn": "2026-09-11",
    "via": "crossref",
    "metadataMatches": true,
    "resolvedTitle": "A synthetic fibrin cross-linking polymer for modulating clot properties and inducing hemostasis",
    "note": "Crossref record found; PubMed id 25739763 located by DOI."
   },
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    "method": "source record generated from the live Crossref work record and a PubMed id lookup by DOI (scripts/seed/2026-09-11-scarless-skin.mjs)",
    "date": "2026-09-11"
   },
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  },
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   "id": "hrm:source/driskell-2013-nature",
   "type": "source",
   "citation": "Driskell et al., Nature, 2013",
   "title": "Distinct fibroblast lineages determine dermal architecture in skin development and repair",
   "authors": "Driskell Ryan R.; Lichtenberger Beate M.; Hoste Esther; Kretzschmar Kai; Simons Ben D.; Charalambous Marika; Ferron Sacri R.; Herault Yann; Pavlovic Guillaume; Ferguson-Smith Anne C.; Watt Fiona M.",
   "venue": "Nature",
   "year": 2013,
   "kind": "article",
   "doi": "10.1038/nature12783",
   "pmid": "24336287",
   "url": "https://doi.org/10.1038/nature12783",
   "license": "http://www.springer.com/tdm",
   "resolution": {
    "resolved": true,
    "checkedOn": "2026-09-11",
    "via": "crossref",
    "metadataMatches": true,
    "resolvedTitle": "Distinct fibroblast lineages determine dermal architecture in skin development and repair",
    "note": "Crossref record found; PubMed id 24336287 located by DOI."
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     "name": "Claude Code session e7dc5601 (Anthropic)",
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     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
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    "method": "source record generated from the live Crossref work record and a PubMed id lookup by DOI (scripts/seed/2026-09-11-scarless-skin.mjs)",
    "date": "2026-09-11"
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  },
  {
   "id": "hrm:source/eming-2014-scitranslmed",
   "type": "source",
   "citation": "Eming et al., Science Translational Medicine, 2014",
   "title": "Wound repair and regeneration: Mechanisms, signaling, and translation",
   "authors": "Eming Sabine A.; Martin Paul; Tomic-Canic Marjana",
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   "year": 2001,
   "kind": "article",
   "doi": "10.2337/diacare.24.2.290",
   "pmid": "11213881",
   "url": "https://doi.org/10.2337/diacare.24.2.290",
   "resolution": {
    "resolved": true,
    "checkedOn": "2026-09-11",
    "via": "crossref",
    "metadataMatches": true,
    "resolvedTitle": "Graftskin, a Human Skin Equivalent, Is Effective in the Management of Noninfected Neuropathic Diabetic Foot Ulcers",
    "note": "Crossref record found; PubMed id 11213881 located by DOI."
   },
   "provenance": {
    "proposedBy": {
     "type": "ai",
     "name": "Claude Code session e7dc5601 (Anthropic)",
     "model": "claude-opus-5",
     "session": "e7dc5601-1690-47c6-bf13-9ca150d31960"
    },
    "method": "source record generated from the live Crossref work record and a PubMed id lookup by DOI (scripts/seed/2026-09-11-scarless-skin.mjs)",
    "date": "2026-09-11"
   },
   "derivedRelations": {
    "citedBy": [
     "hrm:claim/graftskin-raises-diabetic-ulcer-closure"
    ]
   }
  }
 ],
 "analysis": {
  "method": "structural only — see scripts/lib/graph-analysis.mjs; no probabilities, costs or forecasts are computed",
  "rankedQuestions": [
   {
    "id": "hrm:question/en1-inhibition-translates-to-human-skin",
    "question": "Does blocking Engrailed-1 activation (mechanotransduction/YAP inhibition) produce regeneration with appendages and native matrix in porcine or human skin, as it does in mouse?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/dermal-architecture-regeneration-without-scar",
     "hrm:capability/fibrogenic-fibroblast-lineage-control",
     "hrm:capability/native-ecm-organisation-reconstruction",
     "hrm:goal/scarless-skin-repair"
    ],
    "downstreamGoals": 5,
    "downstreamCapabilities": 3,
    "downstreamTotal": 8,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/dermal-architecture-regeneration-without-scar",
      "rung": "L2"
     },
     {
      "id": "hrm:capability/fibrogenic-fibroblast-lineage-control",
      "rung": "L2"
     },
     {
      "id": "hrm:capability/native-ecm-organisation-reconstruction",
      "rung": "L2"
     }
    ],
    "testedBy": [
     "hrm:experiment/verteporfin-porcine-full-thickness-wound"
    ],
    "projections": [
     "universal-repair",
     "rejuvenation"
    ],
    "rank": 1
   },
   {
    "id": "hrm:question/organised-microvasculature-in-thick-regenerated-tissue",
    "question": "Can an organised, hierarchical, perfused microvascular network be induced throughout regenerated or engineered dermis thicker than the diffusion limit, in humans, with normal geometry and long-term stability?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
     "hrm:capability/organised-microvascular-network-in-regenerated-dermis"
    ],
    "downstreamGoals": 4,
    "downstreamCapabilities": 2,
    "downstreamTotal": 6,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
      "rung": "L2"
     },
     {
      "id": "hrm:capability/organised-microvascular-network-in-regenerated-dermis",
      "rung": "L2"
     }
    ],
    "testedBy": [],
    "projections": [
     "universal-repair",
     "rejuvenation"
    ],
    "rank": 2
   },
   {
    "id": "hrm:question/what-limits-regeneration-in-mus-and-human",
    "question": "What, mechanistically, stops laboratory mice and humans from regenerating skin the way spiny mice do — the immune response, the matrix, the fibroblast lineage, or something else?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/fibrogenic-fibroblast-lineage-control",
     "hrm:capability/inflammation-phase-control-for-regeneration",
     "hrm:capability/mammalian-scar-free-regeneration-target-state",
     "hrm:goal/scarless-skin-repair",
     "hrm:goal/skin-biological-control"
    ],
    "downstreamGoals": 3,
    "downstreamCapabilities": 3,
    "downstreamTotal": 6,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/fibrogenic-fibroblast-lineage-control",
      "rung": "L2"
     },
     {
      "id": "hrm:capability/inflammation-phase-control-for-regeneration",
      "rung": null
     },
     {
      "id": "hrm:capability/mammalian-scar-free-regeneration-target-state",
      "rung": "L2"
     }
    ],
    "testedBy": [
     "hrm:experiment/acomys-vs-mus-matched-wound-atlas"
    ],
    "projections": [
     "universal-repair",
     "rejuvenation"
    ],
    "rank": 3
   },
   {
    "id": "hrm:question/regenerated-skin-sensory-reinnervation",
    "question": "Does regenerated or grafted skin regain sensory innervation comparable to uninjured skin, and what limits it?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/cutaneous-sensory-reinnervation"
    ],
    "downstreamGoals": 4,
    "downstreamCapabilities": 1,
    "downstreamTotal": 5,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/cutaneous-sensory-reinnervation",
      "rung": "L1"
     }
    ],
    "testedBy": [],
    "projections": [
     "universal-repair",
     "rejuvenation"
    ],
    "rank": 4
   },
   {
    "id": "hrm:question/pluripotent-derived-skin-engrafts-in-humans",
    "question": "Can pluripotent-stem-cell-derived, appendage-bearing skin engraft in a human, vascularise, and remain stable?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/appendage-bearing-skin-from-pluripotent-cells"
    ],
    "downstreamGoals": 4,
    "downstreamCapabilities": 1,
    "downstreamTotal": 5,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
      "rung": "L2"
     }
    ],
    "testedBy": [],
    "projections": [
     "universal-repair",
     "rejuvenation"
    ],
    "rank": 5
   },
   {
    "id": "hrm:question/wound-induced-hair-neogenesis-in-human-skin",
    "question": "Can de novo hair follicle neogenesis occur in adult human wounds, or is it lost with development?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/hair-follicle-neogenesis-after-wounding"
    ],
    "downstreamGoals": 4,
    "downstreamCapabilities": 1,
    "downstreamTotal": 5,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/hair-follicle-neogenesis-after-wounding",
      "rung": "L2"
     }
    ],
    "testedBy": [
     "hrm:experiment/wihn-human-xenograft-large-wound"
    ],
    "projections": [
     "universal-repair",
     "rejuvenation"
    ],
    "rank": 6
   },
   {
    "id": "hrm:question/dermal-adipocyte-regeneration-in-human-wounds",
    "question": "Can dermal adipocyte regeneration from myofibroblasts be induced in human wounds?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/dermal-adipocyte-regeneration"
    ],
    "downstreamGoals": 3,
    "downstreamCapabilities": 1,
    "downstreamTotal": 4,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/dermal-adipocyte-regeneration",
      "rung": "L2"
     }
    ],
    "testedBy": [],
    "projections": [
     "universal-repair",
     "rejuvenation"
    ],
    "rank": 7
   },
   {
    "id": "hrm:question/partial-reprogramming-human-safety",
    "question": "Can partial epigenetic reprogramming rejuvenate a human tissue without dedifferentiation, loss of cell identity or tumour formation?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/cell-identity-retention-under-partial-reprogramming",
     "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
     "hrm:goal/systemic-rejuvenation"
    ],
    "downstreamGoals": 2,
    "downstreamCapabilities": 2,
    "downstreamTotal": 4,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/cell-identity-retention-under-partial-reprogramming",
      "rung": "L2"
     },
     {
      "id": "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
      "rung": "L2"
     }
    ],
    "testedBy": [
     "hrm:experiment/er-100-phase-1-optic-neuropathies"
    ],
    "projections": [
     "rejuvenation"
    ],
    "rank": 8
   },
   {
    "id": "hrm:question/gene-corrected-epidermal-graft-long-term-safety",
    "question": "Do gene-corrected epidermal stem-cell grafts remain stable and free of clonal or malignant events beyond five years?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/epidermis-gene-corrected-stem-cell-replacement"
    ],
    "downstreamGoals": 3,
    "downstreamCapabilities": 1,
    "downstreamTotal": 4,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/epidermis-gene-corrected-stem-cell-replacement",
      "rung": "L4"
     }
    ],
    "testedBy": [
     "hrm:experiment/gene-corrected-epidermal-graft-long-term-registry"
    ],
    "projections": [
     "universal-repair"
    ],
    "rank": 9
   },
   {
    "id": "hrm:question/topical-gene-delivery-generalises-beyond-eb",
    "question": "Does topical HSV-vector gene delivery to keratinocytes generalise to other genes and non-EB indications, and by unaffiliated groups?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery"
    ],
    "downstreamGoals": 3,
    "downstreamCapabilities": 1,
    "downstreamTotal": 4,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery",
      "rung": "L4"
     }
    ],
    "testedBy": [],
    "projections": [
     "universal-repair"
    ],
    "rank": 10
   },
   {
    "id": "hrm:question/why-avotermin-phase-3-failed",
    "question": "Why did avotermin (TGF-β3) fail in phase 3 after positive double-blind phase I/II and phase II results — and where are the phase 3 data?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/pharmacological-scar-reduction-in-humans",
     "hrm:goal/skin-biological-control"
    ],
    "downstreamGoals": 3,
    "downstreamCapabilities": 1,
    "downstreamTotal": 4,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/pharmacological-scar-reduction-in-humans",
      "rung": "L4"
     }
    ],
    "testedBy": [],
    "projections": [
     "universal-repair"
    ],
    "rank": 11
   },
   {
    "id": "hrm:question/fetal-conditions-reproducible-in-adult-skin",
    "question": "Which features of early-gestation fetal wound healing are causal for scarlessness, and can they be reproduced in adult skin?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/fetal-scarless-healing-target-state"
    ],
    "downstreamGoals": 3,
    "downstreamCapabilities": 1,
    "downstreamTotal": 4,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/fetal-scarless-healing-target-state",
      "rung": "L5"
     }
    ],
    "testedBy": [],
    "projections": [
     "universal-repair",
     "rejuvenation"
    ],
    "rank": 12
   },
   {
    "id": "hrm:question/nondestructive-fibroblast-state-readout-in-human-wounds",
    "question": "Can fibroblast state (fibrotic versus regenerative trajectory) be read non-destructively in a living human wound early enough to intervene?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/fibroblast-state-sensing-in-living-wound"
    ],
    "downstreamGoals": 3,
    "downstreamCapabilities": 1,
    "downstreamTotal": 4,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/fibroblast-state-sensing-in-living-wound",
      "rung": null
     }
    ],
    "testedBy": [],
    "projections": [
     "universal-repair",
     "rejuvenation"
    ],
    "rank": 13
   },
   {
    "id": "hrm:question/reliable-biofilm-eradication-in-chronic-wounds",
    "question": "Can established polymicrobial biofilm be reliably eradicated from chronic human wounds?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/chronic-wound-biofilm-eradication",
     "hrm:goal/skin-contamination-control"
    ],
    "downstreamGoals": 3,
    "downstreamCapabilities": 1,
    "downstreamTotal": 4,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/chronic-wound-biofilm-eradication",
      "rung": null
     }
    ],
    "testedBy": [],
    "projections": [
     "universal-repair"
    ],
    "rank": 14
   },
   {
    "id": "hrm:question/established-scar-remodelling-to-native-architecture",
    "question": "Can a mature dermal scar be remodelled into dermis with native matrix organisation and appendages?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/established-dermal-scar-reversal",
     "hrm:goal/established-scar-repair"
    ],
    "downstreamGoals": 2,
    "downstreamCapabilities": 1,
    "downstreamTotal": 3,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/established-dermal-scar-reversal",
      "rung": "L0"
     }
    ],
    "testedBy": [],
    "projections": [
     "universal-repair",
     "rejuvenation"
    ],
    "rank": 15
   },
   {
    "id": "hrm:question/rejuvenation-reach-beyond-eye-and-liver",
    "question": "Can a rejuvenation payload reach tissues beyond the eye and liver — heart, brain, muscle — at useful efficiency?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/systemic-cell-type-specific-delivery",
     "hrm:goal/systemic-rejuvenation"
    ],
    "downstreamGoals": 2,
    "downstreamCapabilities": 1,
    "downstreamTotal": 3,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/systemic-cell-type-specific-delivery",
      "rung": "L4"
     }
    ],
    "testedBy": [],
    "projections": [
     "rejuvenation"
    ],
    "rank": 16
   },
   {
    "id": "hrm:question/cancer-risk-of-repeated-partial-reprogramming",
    "question": "What is the cancer risk of repeated partial reprogramming in aged human tissue, and can it be bounded by a stopping rule?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/cancer-risk-control-under-rejuvenation",
     "hrm:goal/systemic-rejuvenation"
    ],
    "downstreamGoals": 2,
    "downstreamCapabilities": 1,
    "downstreamTotal": 3,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/cancer-risk-control-under-rejuvenation",
      "rung": null
     }
    ],
    "testedBy": [],
    "projections": [
     "rejuvenation"
    ],
    "rank": 17
   },
   {
    "id": "hrm:question/rejuvenated-state-persistence-and-redosing",
    "question": "Does a rejuvenated state persist after treatment stops, and can treatment be repeated without cumulative harm?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/rejuvenated-state-persistence",
     "hrm:goal/systemic-rejuvenation"
    ],
    "downstreamGoals": 2,
    "downstreamCapabilities": 1,
    "downstreamTotal": 3,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/rejuvenated-state-persistence",
      "rung": null
     }
    ],
    "testedBy": [],
    "projections": [
     "rejuvenation"
    ],
    "rank": 18
   },
   {
    "id": "hrm:question/healthy-target-state-for-aged-tissue",
    "question": "What counts as the healthy target state for an aged person's tissue — youthful architecture, age-appropriate function, or something the person defines?",
    "state": "open",
    "blocksDirectly": [
     "hrm:goal/rejuvenation",
     "hrm:goal/systemic-rejuvenation"
    ],
    "downstreamGoals": 2,
    "downstreamCapabilities": 0,
    "downstreamTotal": 2,
    "directlyBlockedRungs": [],
    "testedBy": [],
    "projections": [
     "rejuvenation"
    ],
    "rank": 19
   },
   {
    "id": "hrm:question/skin-substitutes-improve-scar-quality-not-just-closure",
    "question": "Do bioengineered skin substitutes improve the quality of the healed skin (scar scale, appendages, sensation) rather than only the rate of closure?",
    "state": "open",
    "blocksDirectly": [
     "hrm:capability/dermal-substitute-for-chronic-wound-closure"
    ],
    "downstreamGoals": 0,
    "downstreamCapabilities": 1,
    "downstreamTotal": 1,
    "directlyBlockedRungs": [
     {
      "id": "hrm:capability/dermal-substitute-for-chronic-wound-closure",
      "rung": "L5"
     }
    ],
    "testedBy": [
     "hrm:experiment/skin-substitute-scar-quality-rct"
    ],
    "projections": [
     "universal-repair"
    ],
    "rank": 20
   }
  ],
  "criticalPaths": [
   {
    "goal": "hrm:goal/established-scar-repair",
    "requiredCapabilities": 6,
    "bindingConstraints": [
     {
      "id": "hrm:capability/established-dermal-scar-reversal",
      "name": "Remodel an established scar into native dermis",
      "rung": "L0",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/established-scar-repair"
     }
    ],
    "andRequirements": [
     {
      "id": "hrm:capability/established-dermal-scar-reversal",
      "name": "Remodel an established scar into native dermis",
      "rung": "L0",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/established-scar-repair"
     },
     {
      "id": "hrm:capability/cutaneous-sensory-reinnervation",
      "name": "Restore sensory innervation of regenerated skin",
      "rung": "L1",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/established-scar-repair"
     },
     {
      "id": "hrm:capability/native-ecm-organisation-reconstruction",
      "name": "Reconstruct native extracellular-matrix organisation",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/established-scar-repair"
     },
     {
      "id": "hrm:capability/organised-microvascular-network-in-regenerated-dermis",
      "name": "Grow an organised, perfused microvascular network in thick regenerated tissue",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/established-scar-repair"
     }
    ],
    "orGroups": [
     {
      "via": "hrm:goal/established-scar-repair",
      "note": "Appendages must come from somewhere: neogenesis in the remodelled tissue or a graft.",
      "bestRung": "L2",
      "members": [
       {
        "id": "hrm:capability/hair-follicle-neogenesis-after-wounding",
        "name": "Regenerate new hair follicles in a healed wound",
        "rung": "L2",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
        "name": "Build appendage-bearing human skin from pluripotent stem cells",
        "rung": "L2",
        "basis": "claims"
       }
      ]
     }
    ],
    "ungraded": [],
    "reading": "bindingConstraints are the AND-required capabilities at the lowest rung: the goal cannot be closer than they are. orGroups list alternatives where clearing one member suffices. Nothing here is a probability."
   },
   {
    "goal": "hrm:goal/rejuvenation",
    "requiredCapabilities": 7,
    "bindingConstraints": [
     {
      "id": "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
      "name": "Reset a tissue's epigenetic age in vivo without loss of function",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/systemic-rejuvenation"
     },
     {
      "id": "hrm:capability/cell-identity-retention-under-partial-reprogramming",
      "name": "Rejuvenate cells while they keep their identity",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/systemic-rejuvenation"
     }
    ],
    "andRequirements": [
     {
      "id": "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
      "name": "Reset a tissue's epigenetic age in vivo without loss of function",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/systemic-rejuvenation"
     },
     {
      "id": "hrm:capability/cell-identity-retention-under-partial-reprogramming",
      "name": "Rejuvenate cells while they keep their identity",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/systemic-rejuvenation"
     }
    ],
    "orGroups": [
     {
      "via": "hrm:goal/systemic-rejuvenation",
      "note": "OR-group: one delivery route sufficing for the tissue in question; nobody knows which will succeed. cns-neuron--reach is the v0.2 grid cell backed by the 16 CNS routes.",
      "bestRung": "L4",
      "members": [
       {
        "id": "hrm:capability/systemic-cell-type-specific-delivery",
        "name": "Deliver a payload to a chosen cell type throughout the body",
        "rung": "L4",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/cns-neuron--reach",
        "name": "Central neuron: reach",
        "rung": "L4",
        "basis": "claims"
       }
      ]
     }
    ],
    "ungraded": [
     {
      "id": "hrm:capability/cancer-risk-control-under-rejuvenation",
      "name": "Keep cancer risk acceptable while rejuvenating tissue",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/systemic-rejuvenation"
     },
     {
      "id": "hrm:capability/rejuvenated-state-persistence",
      "name": "Make a rejuvenated state persist, or re-dose safely",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/systemic-rejuvenation"
     }
    ],
    "reading": "bindingConstraints are the AND-required capabilities at the lowest rung: the goal cannot be closer than they are. orGroups list alternatives where clearing one member suffices. Nothing here is a probability."
   },
   {
    "goal": "hrm:goal/scarless-skin-repair",
    "requiredCapabilities": 28,
    "bindingConstraints": [
     {
      "id": "hrm:capability/cutaneous-sensory-reinnervation",
      "name": "Restore sensory innervation of regenerated skin",
      "rung": "L1",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     }
    ],
    "andRequirements": [
     {
      "id": "hrm:capability/cutaneous-sensory-reinnervation",
      "name": "Restore sensory innervation of regenerated skin",
      "rung": "L1",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/dermal-architecture-regeneration-without-scar",
      "name": "Regenerate dermis with appendages and no scar after full-thickness injury",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/native-ecm-organisation-reconstruction",
      "name": "Reconstruct native extracellular-matrix organisation",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/organised-microvascular-network-in-regenerated-dermis",
      "name": "Grow an organised, perfused microvascular network in thick regenerated tissue",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/hair-follicle-neogenesis-after-wounding",
      "name": "Regenerate new hair follicles in a healed wound",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/dermal-adipocyte-regeneration",
      "name": "Regenerate dermal adipocytes in a healing wound",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/melanocyte--edit",
      "name": "Melanocyte: edit",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/fibrogenic-fibroblast-lineage-control",
      "name": "Control the fibroblast lineage that produces scar",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/mammalian-scar-free-regeneration-target-state",
      "name": "An adult mammal that regenerates skin without scar (existence proof)",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/pharmacological-scar-reduction-in-humans",
      "name": "Reduce scarring pharmacologically in human wounds",
      "rung": "L4",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/skin-haemostasis",
      "name": "Stop bleeding from a skin injury",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-immediate-stabilisation"
     },
     {
      "id": "hrm:capability/temporary-barrier-restoration",
      "name": "Restore a temporary barrier over a wound",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-immediate-stabilisation"
     },
     {
      "id": "hrm:capability/acute-wound-infection-control",
      "name": "Prevent and treat acute wound infection",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-contamination-control"
     },
     {
      "id": "hrm:capability/fetal-scarless-healing-target-state",
      "name": "Human skin that heals without scar exists (early-gestation fetus)",
      "rung": "L5",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/wound-bed-assessment-in-vivo",
      "name": "Assess wound depth, perfusion and infection in a living patient",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-functional-restoration"
     },
     {
      "id": "hrm:capability/regeneration-verification-histology-and-scar-scales",
      "name": "Verify a repair outcome by histology and validated scar scales",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-functional-restoration"
     }
    ],
    "orGroups": [
     {
      "via": "hrm:goal/skin-structural-reconstruction",
      "note": "Epidermal restoration: any of three demonstrated routes, chosen by cause.",
      "bestRung": "L5",
      "members": [
       {
        "id": "hrm:capability/epidermis-replacement-cultured-autograft",
        "name": "Replace lost epidermis with cultured autologous keratinocytes",
        "rung": "L5",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/epidermis-gene-corrected-stem-cell-replacement",
        "name": "Regenerate an entire epidermis from gene-corrected autologous stem cells",
        "rung": "L4",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery",
        "name": "Deliver a therapeutic gene to keratinocytes in situ by topical application",
        "rung": "L4",
        "basis": "claims"
       }
      ]
     },
     {
      "via": "hrm:goal/skin-structural-reconstruction",
      "note": "Appendages: regenerate in place OR graft an appendage-bearing construct.",
      "bestRung": "L2",
      "members": [
       {
        "id": "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
        "name": "Build appendage-bearing human skin from pluripotent stem cells",
        "rung": "L2",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/hair-follicle-neogenesis-after-wounding",
        "name": "Regenerate new hair follicles in a healed wound",
        "rung": "L2",
        "basis": "claims"
       }
      ]
     }
    ],
    "ungraded": [
     {
      "id": "hrm:capability/chronic-wound-biofilm-eradication",
      "name": "Eradicate established biofilm in a chronic wound",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/skin-contamination-control"
     },
     {
      "id": "hrm:capability/inflammation-phase-control-for-regeneration",
      "name": "Steer the inflammatory phase toward regeneration",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/fibroblast-state-sensing-in-living-wound",
      "name": "Measure fibroblast state in a living human wound",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/skin-functional-restoration"
     }
    ],
    "reading": "bindingConstraints are the AND-required capabilities at the lowest rung: the goal cannot be closer than they are. orGroups list alternatives where clearing one member suffices. Nothing here is a probability."
   },
   {
    "goal": "hrm:goal/skin-biological-control",
    "requiredCapabilities": 5,
    "bindingConstraints": [
     {
      "id": "hrm:capability/fibrogenic-fibroblast-lineage-control",
      "name": "Control the fibroblast lineage that produces scar",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/mammalian-scar-free-regeneration-target-state",
      "name": "An adult mammal that regenerates skin without scar (existence proof)",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     }
    ],
    "andRequirements": [
     {
      "id": "hrm:capability/fibrogenic-fibroblast-lineage-control",
      "name": "Control the fibroblast lineage that produces scar",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/mammalian-scar-free-regeneration-target-state",
      "name": "An adult mammal that regenerates skin without scar (existence proof)",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/pharmacological-scar-reduction-in-humans",
      "name": "Reduce scarring pharmacologically in human wounds",
      "rung": "L4",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/fetal-scarless-healing-target-state",
      "name": "Human skin that heals without scar exists (early-gestation fetus)",
      "rung": "L5",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     }
    ],
    "orGroups": [],
    "ungraded": [
     {
      "id": "hrm:capability/inflammation-phase-control-for-regeneration",
      "name": "Steer the inflammatory phase toward regeneration",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/skin-biological-control"
     }
    ],
    "reading": "bindingConstraints are the AND-required capabilities at the lowest rung: the goal cannot be closer than they are. orGroups list alternatives where clearing one member suffices. Nothing here is a probability."
   },
   {
    "goal": "hrm:goal/skin-contamination-control",
    "requiredCapabilities": 2,
    "bindingConstraints": [
     {
      "id": "hrm:capability/acute-wound-infection-control",
      "name": "Prevent and treat acute wound infection",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-contamination-control"
     }
    ],
    "andRequirements": [
     {
      "id": "hrm:capability/acute-wound-infection-control",
      "name": "Prevent and treat acute wound infection",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-contamination-control"
     }
    ],
    "orGroups": [],
    "ungraded": [
     {
      "id": "hrm:capability/chronic-wound-biofilm-eradication",
      "name": "Eradicate established biofilm in a chronic wound",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/skin-contamination-control"
     }
    ],
    "reading": "bindingConstraints are the AND-required capabilities at the lowest rung: the goal cannot be closer than they are. orGroups list alternatives where clearing one member suffices. Nothing here is a probability."
   },
   {
    "goal": "hrm:goal/skin-functional-restoration",
    "requiredCapabilities": 3,
    "bindingConstraints": [
     {
      "id": "hrm:capability/wound-bed-assessment-in-vivo",
      "name": "Assess wound depth, perfusion and infection in a living patient",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-functional-restoration"
     },
     {
      "id": "hrm:capability/regeneration-verification-histology-and-scar-scales",
      "name": "Verify a repair outcome by histology and validated scar scales",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-functional-restoration"
     }
    ],
    "andRequirements": [
     {
      "id": "hrm:capability/wound-bed-assessment-in-vivo",
      "name": "Assess wound depth, perfusion and infection in a living patient",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-functional-restoration"
     },
     {
      "id": "hrm:capability/regeneration-verification-histology-and-scar-scales",
      "name": "Verify a repair outcome by histology and validated scar scales",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-functional-restoration"
     }
    ],
    "orGroups": [],
    "ungraded": [
     {
      "id": "hrm:capability/fibroblast-state-sensing-in-living-wound",
      "name": "Measure fibroblast state in a living human wound",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/skin-functional-restoration"
     }
    ],
    "reading": "bindingConstraints are the AND-required capabilities at the lowest rung: the goal cannot be closer than they are. orGroups list alternatives where clearing one member suffices. Nothing here is a probability."
   },
   {
    "goal": "hrm:goal/skin-immediate-stabilisation",
    "requiredCapabilities": 2,
    "bindingConstraints": [
     {
      "id": "hrm:capability/skin-haemostasis",
      "name": "Stop bleeding from a skin injury",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-immediate-stabilisation"
     },
     {
      "id": "hrm:capability/temporary-barrier-restoration",
      "name": "Restore a temporary barrier over a wound",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-immediate-stabilisation"
     }
    ],
    "andRequirements": [
     {
      "id": "hrm:capability/skin-haemostasis",
      "name": "Stop bleeding from a skin injury",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-immediate-stabilisation"
     },
     {
      "id": "hrm:capability/temporary-barrier-restoration",
      "name": "Restore a temporary barrier over a wound",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-immediate-stabilisation"
     }
    ],
    "orGroups": [],
    "ungraded": [],
    "reading": "bindingConstraints are the AND-required capabilities at the lowest rung: the goal cannot be closer than they are. orGroups list alternatives where clearing one member suffices. Nothing here is a probability."
   },
   {
    "goal": "hrm:goal/skin-structural-reconstruction",
    "requiredCapabilities": 11,
    "bindingConstraints": [
     {
      "id": "hrm:capability/cutaneous-sensory-reinnervation",
      "name": "Restore sensory innervation of regenerated skin",
      "rung": "L1",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     }
    ],
    "andRequirements": [
     {
      "id": "hrm:capability/cutaneous-sensory-reinnervation",
      "name": "Restore sensory innervation of regenerated skin",
      "rung": "L1",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/dermal-architecture-regeneration-without-scar",
      "name": "Regenerate dermis with appendages and no scar after full-thickness injury",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/native-ecm-organisation-reconstruction",
      "name": "Reconstruct native extracellular-matrix organisation",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/organised-microvascular-network-in-regenerated-dermis",
      "name": "Grow an organised, perfused microvascular network in thick regenerated tissue",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/hair-follicle-neogenesis-after-wounding",
      "name": "Regenerate new hair follicles in a healed wound",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/dermal-adipocyte-regeneration",
      "name": "Regenerate dermal adipocytes in a healing wound",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/melanocyte--edit",
      "name": "Melanocyte: edit",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     }
    ],
    "orGroups": [
     {
      "via": "hrm:goal/skin-structural-reconstruction",
      "note": "Epidermal restoration: any of three demonstrated routes, chosen by cause.",
      "bestRung": "L5",
      "members": [
       {
        "id": "hrm:capability/epidermis-replacement-cultured-autograft",
        "name": "Replace lost epidermis with cultured autologous keratinocytes",
        "rung": "L5",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/epidermis-gene-corrected-stem-cell-replacement",
        "name": "Regenerate an entire epidermis from gene-corrected autologous stem cells",
        "rung": "L4",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery",
        "name": "Deliver a therapeutic gene to keratinocytes in situ by topical application",
        "rung": "L4",
        "basis": "claims"
       }
      ]
     },
     {
      "via": "hrm:goal/skin-structural-reconstruction",
      "note": "Appendages: regenerate in place OR graft an appendage-bearing construct.",
      "bestRung": "L2",
      "members": [
       {
        "id": "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
        "name": "Build appendage-bearing human skin from pluripotent stem cells",
        "rung": "L2",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/hair-follicle-neogenesis-after-wounding",
        "name": "Regenerate new hair follicles in a healed wound",
        "rung": "L2",
        "basis": "claims"
       }
      ]
     }
    ],
    "ungraded": [],
    "reading": "bindingConstraints are the AND-required capabilities at the lowest rung: the goal cannot be closer than they are. orGroups list alternatives where clearing one member suffices. Nothing here is a probability."
   },
   {
    "goal": "hrm:goal/systemic-rejuvenation",
    "requiredCapabilities": 6,
    "bindingConstraints": [
     {
      "id": "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
      "name": "Reset a tissue's epigenetic age in vivo without loss of function",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/systemic-rejuvenation"
     },
     {
      "id": "hrm:capability/cell-identity-retention-under-partial-reprogramming",
      "name": "Rejuvenate cells while they keep their identity",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/systemic-rejuvenation"
     }
    ],
    "andRequirements": [
     {
      "id": "hrm:capability/safe-partial-epigenetic-reprogramming-in-vivo",
      "name": "Reset a tissue's epigenetic age in vivo without loss of function",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/systemic-rejuvenation"
     },
     {
      "id": "hrm:capability/cell-identity-retention-under-partial-reprogramming",
      "name": "Rejuvenate cells while they keep their identity",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/systemic-rejuvenation"
     }
    ],
    "orGroups": [
     {
      "via": "hrm:goal/systemic-rejuvenation",
      "note": "OR-group: one delivery route sufficing for the tissue in question; nobody knows which will succeed. cns-neuron--reach is the v0.2 grid cell backed by the 16 CNS routes.",
      "bestRung": "L4",
      "members": [
       {
        "id": "hrm:capability/systemic-cell-type-specific-delivery",
        "name": "Deliver a payload to a chosen cell type throughout the body",
        "rung": "L4",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/cns-neuron--reach",
        "name": "Central neuron: reach",
        "rung": "L4",
        "basis": "claims"
       }
      ]
     }
    ],
    "ungraded": [
     {
      "id": "hrm:capability/cancer-risk-control-under-rejuvenation",
      "name": "Keep cancer risk acceptable while rejuvenating tissue",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/systemic-rejuvenation"
     },
     {
      "id": "hrm:capability/rejuvenated-state-persistence",
      "name": "Make a rejuvenated state persist, or re-dose safely",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/systemic-rejuvenation"
     }
    ],
    "reading": "bindingConstraints are the AND-required capabilities at the lowest rung: the goal cannot be closer than they are. orGroups list alternatives where clearing one member suffices. Nothing here is a probability."
   },
   {
    "goal": "hrm:goal/universal-repair",
    "requiredCapabilities": 31,
    "bindingConstraints": [
     {
      "id": "hrm:capability/established-dermal-scar-reversal",
      "name": "Remodel an established scar into native dermis",
      "rung": "L0",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/established-scar-repair"
     }
    ],
    "andRequirements": [
     {
      "id": "hrm:capability/established-dermal-scar-reversal",
      "name": "Remodel an established scar into native dermis",
      "rung": "L0",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/established-scar-repair"
     },
     {
      "id": "hrm:capability/cutaneous-sensory-reinnervation",
      "name": "Restore sensory innervation of regenerated skin",
      "rung": "L1",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/dermal-architecture-regeneration-without-scar",
      "name": "Regenerate dermis with appendages and no scar after full-thickness injury",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/native-ecm-organisation-reconstruction",
      "name": "Reconstruct native extracellular-matrix organisation",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/organised-microvascular-network-in-regenerated-dermis",
      "name": "Grow an organised, perfused microvascular network in thick regenerated tissue",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/hair-follicle-neogenesis-after-wounding",
      "name": "Regenerate new hair follicles in a healed wound",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/dermal-adipocyte-regeneration",
      "name": "Regenerate dermal adipocytes in a healing wound",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/melanocyte--edit",
      "name": "Melanocyte: edit",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-structural-reconstruction"
     },
     {
      "id": "hrm:capability/fibrogenic-fibroblast-lineage-control",
      "name": "Control the fibroblast lineage that produces scar",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/mammalian-scar-free-regeneration-target-state",
      "name": "An adult mammal that regenerates skin without scar (existence proof)",
      "rung": "L2",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/pharmacological-scar-reduction-in-humans",
      "name": "Reduce scarring pharmacologically in human wounds",
      "rung": "L4",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/skin-haemostasis",
      "name": "Stop bleeding from a skin injury",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-immediate-stabilisation"
     },
     {
      "id": "hrm:capability/temporary-barrier-restoration",
      "name": "Restore a temporary barrier over a wound",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-immediate-stabilisation"
     },
     {
      "id": "hrm:capability/acute-wound-infection-control",
      "name": "Prevent and treat acute wound infection",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-contamination-control"
     },
     {
      "id": "hrm:capability/fetal-scarless-healing-target-state",
      "name": "Human skin that heals without scar exists (early-gestation fetus)",
      "rung": "L5",
      "blocked": "science",
      "basis": "claims",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/wound-bed-assessment-in-vivo",
      "name": "Assess wound depth, perfusion and infection in a living patient",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-functional-restoration"
     },
     {
      "id": "hrm:capability/regeneration-verification-histology-and-scar-scales",
      "name": "Verify a repair outcome by histology and validated scar scales",
      "rung": "L5",
      "blocked": "none",
      "basis": "standard-of-care",
      "via": "hrm:goal/skin-functional-restoration"
     }
    ],
    "orGroups": [
     {
      "via": "hrm:goal/skin-structural-reconstruction",
      "note": "Epidermal restoration: any of three demonstrated routes, chosen by cause.",
      "bestRung": "L5",
      "members": [
       {
        "id": "hrm:capability/epidermis-replacement-cultured-autograft",
        "name": "Replace lost epidermis with cultured autologous keratinocytes",
        "rung": "L5",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/epidermis-gene-corrected-stem-cell-replacement",
        "name": "Regenerate an entire epidermis from gene-corrected autologous stem cells",
        "rung": "L4",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/keratinocyte-in-vivo-topical-gene-delivery",
        "name": "Deliver a therapeutic gene to keratinocytes in situ by topical application",
        "rung": "L4",
        "basis": "claims"
       }
      ]
     },
     {
      "via": "hrm:goal/skin-structural-reconstruction",
      "note": "Appendages: regenerate in place OR graft an appendage-bearing construct.",
      "bestRung": "L2",
      "members": [
       {
        "id": "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
        "name": "Build appendage-bearing human skin from pluripotent stem cells",
        "rung": "L2",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/hair-follicle-neogenesis-after-wounding",
        "name": "Regenerate new hair follicles in a healed wound",
        "rung": "L2",
        "basis": "claims"
       }
      ]
     },
     {
      "via": "hrm:goal/established-scar-repair",
      "note": "Appendages must come from somewhere: neogenesis in the remodelled tissue or a graft.",
      "bestRung": "L2",
      "members": [
       {
        "id": "hrm:capability/hair-follicle-neogenesis-after-wounding",
        "name": "Regenerate new hair follicles in a healed wound",
        "rung": "L2",
        "basis": "claims"
       },
       {
        "id": "hrm:capability/appendage-bearing-skin-from-pluripotent-cells",
        "name": "Build appendage-bearing human skin from pluripotent stem cells",
        "rung": "L2",
        "basis": "claims"
       }
      ]
     }
    ],
    "ungraded": [
     {
      "id": "hrm:capability/chronic-wound-biofilm-eradication",
      "name": "Eradicate established biofilm in a chronic wound",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/skin-contamination-control"
     },
     {
      "id": "hrm:capability/inflammation-phase-control-for-regeneration",
      "name": "Steer the inflammatory phase toward regeneration",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/skin-biological-control"
     },
     {
      "id": "hrm:capability/fibroblast-state-sensing-in-living-wound",
      "name": "Measure fibroblast state in a living human wound",
      "rung": null,
      "blocked": null,
      "basis": "ungraded",
      "via": "hrm:goal/skin-functional-restoration"
     }
    ],
    "reading": "bindingConstraints are the AND-required capabilities at the lowest rung: the goal cannot be closer than they are. orGroups list alternatives where clearing one member suffices. Nothing here is a probability."
   }
  ],
  "contradictions": [
   {
    "claim": "hrm:claim/adult-mammalian-wounds-heal-by-scar",
    "contradicts": [
     "hrm:capability/dermal-architecture-regeneration-without-scar"
    ],
    "statement": "Adult mammalian and human skin wounds heal by a fibrotic scar that lacks the appendages and matrix organisation of uninjured skin; this is the default outcome of adult repair."
   },
   {
    "claim": "hrm:claim/no-therapy-reverses-established-fibrosis",
    "contradicts": [
     "hrm:capability/established-dermal-scar-reversal"
    ],
    "statement": "No approved therapy reverses established organ fibrosis; current antifibrotic drugs slow progression, and fibrosis remains a major cause of irreversible organ dysfunction."
   },
   {
    "claim": "hrm:claim/thick-engineered-tissue-vascularisation-unsolved",
    "contradicts": [
     "hrm:capability/organised-microvascular-network-in-regenerated-dermis"
    ],
    "statement": "Vascularisation of engineered tissue beyond the diffusion limit remains an unsolved problem: prevascularisation and angiogenic strategies yield capillary networks in rodent constructs but not organised, stable, clinically usable vasculature in thick human tissue."
   }
  ],
  "grades": {
   "byClass": {
    "control": {
     "n": 6,
     "graded": 4,
     "sumRung": 17,
     "rungs": {
      "L5": 3,
      "L2": 1
     },
     "meanRung": 4.25
    },
    "edit": {
     "n": 46,
     "graded": 45,
     "sumRung": 122,
     "rungs": {
      "L2": 18,
      "L1": 7,
      "L5": 7,
      "L4": 8,
      "L0": 1,
      "L3": 4
     },
     "meanRung": 2.71
    },
    "model": {
     "n": 34,
     "graded": 34,
     "sumRung": 113,
     "rungs": {
      "L2": 9,
      "L5": 5,
      "L3": 7,
      "L4": 12,
      "L1": 1
     },
     "meanRung": 3.32
    },
    "see": {
     "n": 33,
     "graded": 32,
     "sumRung": 129,
     "rungs": {
      "L5": 12,
      "L3": 9,
      "L2": 1,
      "L4": 10
     },
     "meanRung": 4.03
    },
    "reach": {
     "n": 33,
     "graded": 33,
     "sumRung": 117,
     "rungs": {
      "L4": 15,
      "L3": 7,
      "L5": 5,
      "L2": 5,
      "L1": 1
     },
     "meanRung": 3.55
    },
    "verify": {
     "n": 33,
     "graded": 32,
     "sumRung": 129,
     "rungs": {
      "L5": 14,
      "L4": 9,
      "L3": 5,
      "L2": 4
     },
     "meanRung": 4.03
    }
   },
   "byBasis": {
    "standard-of-care": 5,
    "claims": 175,
    "ungraded": 5
   },
   "byBlocked": {
    "none": 70,
    "science": 107,
    "framework": 3
   }
  }
 }
}