health
Organs grown from cells or supplied by engineered animals become routine by 2126.
Last revised Sep 13, 2026.
Current estimate
probability this has happened by each date
The full test below is met by 31 December 2035. Held exactly where cycle 14 put it, deliberately. Everything this cycle learned bears on whether the criterion is eventually satisfiable, and none of it touches the manufacturing floor, which is what excludes this horizon: a quarter of American vascularised solid-organ transplants is on the order of twelve thousand organs a year, the one operating designated-pathogen-free facility has a disclosed target of 125, and two more are under construction. Bridge use lowers the clinical bar but not the number of organs that must physically exist.
The full test below is met by 31 December 2050. Raised from 0.08 on three specific changes: observed graft function in a living human went from 130 to 271 days in nine months, a second organ entered a registration-intent trial when the FDA cleared the EXPRESS heart study on 15 May 2026, and the manufacturing question became a measurable series rather than an unknown. Held back by what that series says - the only commercial-scale capacity figure United Therapeutics ever published, approximately 1,000 organs per year per facility, appeared in the FY2023 annual report and was removed from the two that followed.
The full test below is met by 31 December 2100. Raised from 0.32. Seventy-four years remains where nearly all the probability accrues, and the bridge finding widens the set of worlds that qualify: the criterion can now be satisfied by a manufactured organ that never permanently replaces a human one, provided it is used often enough as a temporary one. The dominant risk over this horizon is unchanged in kind but weaker in force - that the technology succeeds and stays confined to patients who cannot obtain a human organ.
In at least two countries, organs grown from human cells or taken from genetically engineered animals together account for at least 25 percent of all vascularised solid-organ transplants - kidney, heart, liver, lung, pancreas - performed in that country in a year, sustained over three consecutive years, documented by a national transplant registry or a peer-reviewed study using registry data. The registry entry must record which of the two sources supplied the organ, so that the two halves of the claim can also be scored separately. Non-vascularised and tissue-scale products - skin, cartilage, cornea, islet preparations, engineered vessels and heart valves - do not count toward the threshold.
Resolution criteria
- 2035
- The full test below is met by 31 December 2035. Held exactly where cycle 14 put it, deliberately. Everything this cycle learned bears on whether the criterion is eventually satisfiable, and none of it touches the manufacturing floor, which is what excludes this horizon: a quarter of American vascularised solid-organ transplants is on the order of twelve thousand organs a year, the one operating designated-pathogen-free facility has a disclosed target of 125, and two more are under construction. Bridge use lowers the clinical bar but not the number of organs that must physically exist.
- 2050
- The full test below is met by 31 December 2050. Raised from 0.08 on three specific changes: observed graft function in a living human went from 130 to 271 days in nine months, a second organ entered a registration-intent trial when the FDA cleared the EXPRESS heart study on 15 May 2026, and the manufacturing question became a measurable series rather than an unknown. Held back by what that series says - the only commercial-scale capacity figure United Therapeutics ever published, approximately 1,000 organs per year per facility, appeared in the FY2023 annual report and was removed from the two that followed.
- 2100
- The full test below is met by 31 December 2100. Raised from 0.32. Seventy-four years remains where nearly all the probability accrues, and the bridge finding widens the set of worlds that qualify: the criterion can now be satisfied by a manufactured organ that never permanently replaces a human one, provided it is used often enough as a temporary one. The dominant risk over this horizon is unchanged in kind but weaker in force - that the technology succeeds and stays confined to patients who cannot obtain a human organ.
- 2126
- In at least two countries, organs grown from human cells or taken from genetically engineered animals together account for at least 25 percent of all vascularised solid-organ transplants - kidney, heart, liver, lung, pancreas - performed in that country in a year, sustained over three consecutive years, documented by a national transplant registry or a peer-reviewed study using registry data. The registry entry must record which of the two sources supplied the organ, so that the two halves of the claim can also be scored separately. Non-vascularised and tissue-scale products - skin, cartilage, cornea, islet preparations, engineered vessels and heart valves - do not count toward the threshold.
Probability history
| Revised | State | p(2035) | p(2050) | p(2100) |
|---|---|---|---|---|
hf-forecast-0209 | researched | 1% ±0 pts | 10% +2 pts | 37% +5 pts |
hf-forecast-0199 | researched | 1% no prior revision | 8% no prior revision | 32% no prior revision |
hf-forecast-0001 | initial prior | — | — | — |
Strongest evidence for
- The quantity cycle 14 said its whole forecast was downstream of roughly doubled in nine months: a gene-edited pig kidney supported a living man for 271 days without dialysis, against a prior recorded maximum of 130 days, and three of five patients in that series passed eight months (hf-evidence-0186).
- Two of those five patients were transitioned from the pig kidney to a human kidney - the first such transitions - which establishes a clinical use for a graft known in advance not to last, and means those recipients were in fact able to obtain a human organ (hf-evidence-0186).
- A second organ entered a registration-intent trial: the FDA cleared United Therapeutics' EXPRESS heart study on 15 May 2026, with the stated intent of supporting a Biologics License Application (hf-evidence-0188).
- A third kidney programme was registered - EXTEND, NCT07224763, a GGTA1-knockout thymokidney - and eGenesis's RESTORE study was cleared for 33 patients from Q1 2027 (hf-evidence-0186, hf-evidence-0188).
- Manufacturing stopped being an unknown: United Therapeutics discloses a target capacity of up to 125 organs per year for its operating Virginia facility in three consecutive annual reports, with two further facilities under construction in Minnesota and Texas (hf-evidence-0187).
- The shortage that motivates the enterprise is not narrowing everywhere. The United Kingdom kidney waiting list rose from 6,939 to 7,203 while transplants fell from 3,305 to 3,278, the longest list in a decade - and the criterion needs a second country (hf-evidence-0189).
Strongest evidence against
- The positional constraint was measured directly for the first time and confirmed, not relaxed: the 2026 ISHLT cardiac consensus names as eligible only 'Adults unable to receive durable mechanical circulatory support (MCS) or allotransplantation, for whom xenograft is intended as destination therapy', and both registered kidney protocols require either medical ineligibility or a documented sub-five-year probability of receiving a human kidney (hf-evidence-0188).
- No graft anywhere has passed one year of function, and no peer-reviewed survival result has been published from any registered trial; EXPAND's estimated primary completion is October 2028 (hf-evidence-0186).
- The only commercial-scale capacity figure ever disclosed - approximately 1,000 organs per year per future facility - appeared once, in the FY2023 annual report, and was removed in FY2024 and softened again in FY2025, with a hedge word added each year (hf-evidence-0187).
- No developer publishes a per-organ manufacturing cost, and that null survived a directed search of regulatory filings, health-economics literature and payer statements (hf-evidence-0187).
- The narrowing-shortage argument that halved this forecast last cycle survived its organ-axis attack and was strengthened: in the United States, liver, heart and lung all show transplants outrunning waiting-list growth at least as fast as kidney (hf-evidence-0189).
- Still no vascularised solid organ grown from human cells has ever been implanted in a human, so the cell-grown half of the claim rests entirely on the animal half.
- One circulating cost figure and one mis-attributed capacity figure dissolved on second inspection this cycle, which is a reminder that the loudest numbers in this field are the least substantiated (hf-day-0023-takeaway-02).
Present uncertainties
- Whether the stated rule or the observed practice governs who receives a manufactured organ, since the documents restrict it to people who cannot have a human one while two of five recipients went on to receive human ones; and whether manufacturing can reach the tens of thousands of organs a year that two countries at a quarter share would require, on which the only disclosed commercial-scale figure was withdrawn from the company's own filings.
Next discriminating observation
First: the registered inclusion criteria of eGenesis's RESTORE trial when it appears on ClinicalTrials.gov before its Q1 2027 start. If they admit waitlisted patients WITHOUT a low-probability filter, the positional constraint has genuinely moved and the third term of this forecast rises again; if they carry the same filter as EXPAND, the press wording was loose and nothing changed. This is the cleanest, nearest, cheapest test available and it resolves within about two quarters. Second: whether any national registry publishes a data element distinguishing a xenograft episode from an allograft episode, without which the criterion cannot be scored however the world turns out - a scoreability risk that did not exist before bridging did. Third: a reappearance or a permanent absence of a commercial-scale organs-per-year figure in United Therapeutics' FY2026 annual report, due around February 2027, which would say whether the withdrawal was a disclosure trim or a retreat.
Sources
- Cycle 14's first and highest-ranked discriminator fired: xenograft function in a living human went from 130 days to 271 days, and it arrived attached to a clinical strategy the seed had not modelled
Cycle 14 named as its first discriminating observation, by a wide margin, 'the first human xenograft to pass one year of function in a living recipient, or a peer-reviewed report from EXPAND of 24-week survival'. Neither happened exactly, but the underlying quantity moved a long way. Mass General Brigham reports that Tim Andrews, transplanted January 2025 with an eGenesis EGEN-2784 ten-gene-edited porcine kidney, 'successfully lived with the genetically edited kidney for 271 days - during which he did not need dialysis', received a human kidney in January 2026, and that this is 'the longest dialysis-free survival following porcine kidney xenotransplantation in a living human and the first transition to human kidney transplantation'. The same release states that 'no previous studies have documented xenograft survival beyond two months', and cites a Lancet 2026 paper, DOI 10.1016/S0140-6736(26)01295-X. eGenesis's clinical update of 3 September 2026 states that 'Five patients with kidney failure have received EGEN-2784 kidney transplants under Expanded Access since March 2024', that 'Three of these patients have achieved sustained kidney function for more than eight months without the need for dialysis', that 'One patient has surpassed nine months of dialysis independence, establishing a new global record', and that 'Two of the five patients have successfully transitioned to human donor kidney transplants'. The prior maximum this seed had recorded was 130 days, from hf-evidence-0098. No graft anywhere has yet been reported past 365 days. The second half of the discriminator did not fire: the EXPAND registry record NCT06878560 remains RECRUITING with an estimated primary completion of October 2028, and no 24-week survival result has been published.
Limit: Both duration sources are press releases from the parties with an interest in the result, and they are not independent of each other in the way two registries would be: Mass General Brigham performed the transplant and eGenesis supplied the organ. The Lancet paper that would settle it was not read. The durability of the other three patients in the series is given only as 'more than eight months' without individual figures, and the retrieval lane found a genuine unresolved conflict on a second named patient, Bill Stewart, between a '200+ days' interim report and a 'nine months' retrospective, which is recorded here as unreconciled rather than averaged. A count of total human kidney xenotransplant cases could not be reconciled either: two 2026 reviews give six and nine, and both were paywalled at 403 so neither was read.
The master fetched and read the Mass General Brigham release and the eGenesis release directly and quoted them verbatim rather than relying on lane extraction, because this figure carries most of the cycle's movement. The ClinicalTrials.gov record was read by the master through the /api/v2/studies JSON endpoint. The Lancet paper itself was NOT read by anyone - it is paywalled - so the 271-day figure rests on two institutional press releases that agree, not on the primary publication.
- The capacity figure cycle 14 killed is real and sits in three consecutive SEC annual reports - and the commercial-scale figure beside it was quietly withdrawn between them
Cycle 14 recorded that no developer has published an organs-per-year capacity figure, and that one circulating figure of 125 organs per year had been 'hunted to its cited article and killed when the article proved not to contain it'. That conclusion is wrong, and the correction comes from a document class cycle 14 did not open. United Therapeutics states the figure in its own annual report, verbatim and unchanged, in three consecutive fiscal years. FY2023 (accession 0001082554-24-000005): 'When fully operational, we expect this DPF to supply cGMP-compliant xenografts for human clinical trials, with a target capacity of up to 125 organs per year. This facility cost approximately $75 million to construct. We are planning to build additional cGMP DPF facilities at commercial scale, each with target capacities of approximately 1,000 organs per year.' FY2024 (0001082554-25-000005) repeats the 125 and the $75 million, adds Minnesota at 'approximately $105 million', and DROPS the 1,000-organ figure, saying only 'we are planning to build additional, larger cGMP DPF facilities at commercial scale'. FY2025 (0001082554-26-000006) repeats the 125, and softens the same sentence again to 'we are also planning to build additional and potentially larger cGMP DPF facilities for commercial use'. So the clinical-scale number is stable across three years while the only commercial-scale number ever disclosed appears once and is then withdrawn, with a hedge word added each year. A local newspaper reports the Minnesota facility as 65,000 square feet with 'a capacity of 150 animals' and a cost of $110 million, which conflicts with the 10-K's $105 million; both are recorded, neither is resolved.
Limit: A target capacity in a forward-looking business section is an intention, not an observed throughput; no filing states how many organs the Virginia facility has actually produced. The withdrawal of the 1,000-organ figure is a documented change in disclosure language and nothing more - it may reflect a design change, legal caution about forward-looking statements, or an editorial trim, and the filings do not say which. No developer anywhere publishes a per-organ manufacturing cost; that null survived the lane's search and is recorded as still holding. eGenesis discloses no facility size, herd size or capacity at all.
The master byte-verified this personally rather than accepting the lane's report, because the finding overturns an earlier record of this seed. Each 10-K was fetched with curl directly from the SEC EDGAR archive, stripped of markup, and regex-searched for the exact strings; the quoted sentences above are the raw extracted text, not a model summary. The retrieval lane had reached the same 125 figure but disclosed that its reads were model-summarised and explicitly not byte-verified, and it did not find the 1,000-organ sentence or its withdrawal at all.
- Cycle 14's second discriminator did not fire: every protocol and every society consensus still requires the recipient to be someone who cannot get a human organ, and the field's newest consensus re-codifies that deliberately
Cycle 14's second discriminating observation was 'the first enrolment of a xenograft recipient who IS eligible for a human organ, since every case so far has been someone who was not'. It has not fired, and the strongest document says it is not meant to. The 2026 ISHLT Consensus Statement on Clinical Cardiac Xenotransplantation, Journal of Heart and Lung Transplantation, February 2026, restates the society's 2000 position that 'patients entering a trial should either be ineligible for allotransplantation or destination mechanical circulatory support (MCS), or unlikely to survive until a human organ becomes available and for whom MCS as a bridge was not feasible', and then in its own 2026 recommendations names as eligible 'Adults unable to receive durable mechanical circulatory support (MCS) or allotransplantation, for whom xenograft is intended as destination therapy'. Its Table 2 list of populations for a pivotal trial is entirely composed of people who cannot obtain a human heart: elderly over 75, highly sensitized individuals, prior malignancy, tropical cardiomyopathies, amyloidosis, restrictive cardiomyopathy not amenable to MCS, and infants after a Norwood procedure. The registered kidney protocols agree. EXPAND (NCT06878560) and EXTEND (NCT07224763) each admit two groups: Group 1 'Ineligible for conventional allogeneic kidney transplantation due to medical reason(s)', and Group 2 'On an OPTN kidney transplant waitlist (active or inactive status)' but only where the patient is 'More likely to die or go untransplanted within 5 years than receive a kidney transplant as measured by the Kidney Transplant Decision Aid'. United Therapeutics' EXPRESS heart trial, FDA-cleared 15 May 2026, requires 'no remaining therapeutic options'. The IXA kidney position paper is reported to require that the patient 'should be fully acceptable as a candidate for allotransplantation but should be unlikely ever to receive an allograft'. Against this, one partial movement is real and one apparent movement is unverified. The real one: Group 2 formally admits waitlisted patients, so the flat statement that every recipient is allograft-ineligible is no longer accurate as a description of the protocols, though every such patient is still selected for poor prospects. The unverified one: eGenesis's planned RESTORE trial is described in secondary press as enrolling patients aged 50 to 70 'waitlisted for a human donor kidney transplant' with no stated probability filter, but the trial is unregistered, starts in 2027, and no primary source for that wording was reached.
Limit: This is a statement about stated policy, not about practice under pressure, and stated policy is exactly the thing that changes when a technology starts working. The documents describe the FIRST phase of clinical trials; none of them claims to govern what happens after a product is approved, and the ISHLT document calls itself 'a living blueprint'. The RESTORE ambiguity is genuinely unresolved and is the single place a shift could already be underway unseen. Liver work is at extracorporeal perfusion rather than implantation and its eligibility wording was not read at primary level.
The master byte-verified the ISHLT consensus personally with pdftotext against the PDF that its own fetch had saved, and the quoted passages above are the extracted text, not a lane summary or a model paraphrase. The master also read both ClinicalTrials.gov protocol records through the JSON API and the United Therapeutics release directly. The IXA position paper was NOT read by anyone: it was paywalled at 403 and 402 on two hosts, and its quoted requirement is a search summary corroborated across two independent queries, which is weaker than everything else in this record. The FDA advisory-committee route was checked directly by the master and returned a hard null: the only two 2026 meetings of the Cellular, Tissue and Gene Therapies Advisory Committee concern a Duchenne cardiomyopathy therapy and a melanoma therapy, and neither concerns xenotransplantation.
- The seed's own headline argument was attacked on two axes and survived one: the narrowing shortage generalises across organs but not across countries, and the United Kingdom is currently moving the other way
Cycle 14 lowered this forecast substantially on the argument that the shortage motivating manufactured organs is narrowing, and computed that argument from United States kidney data alone while the criterion scores five organs in at least two countries. A lane was assigned to break it on both axes. ON THE ORGAN AXIS THE ATTACK FAILED, and the failure strengthens cycle 14: in the United States between 2013 and 2024 the liver waiting list FELL from 28,484 to 25,538 while liver transplants rose from 6,455 to 11,458; heart went 7,456 to 9,444 against 2,554 to 4,636 transplants; lung went 4,257 to 4,775 against 1,947 to 3,404. Kidney's own 139,715 to 147,091 against 17,658 to 28,492 is the LEAST favourable of the four, so restricting the argument to kidney was not cherry-picking. ON THE COUNTRY AXIS THE ATTACK HELD. The United Kingdom, the only non-American kidney registry for which a recent dated two-point trend was obtained, is moving the opposite way: the waiting list rose from 6,939 in 2024/25 to 7,203 in 2025/26 while transplants fell from 3,305 to 3,278, the longest list in a decade, reversing an earlier five-year period in which the median wait fell 18 percent from 1,153 to 944 days. Canada narrows on wait time only, 3.8 years in 2014 to 3.4 in 2023. Germany, Japan, Spain and China returned severity snapshots with no comparable trend.
Limit: An arithmetic inconsistency is left open rather than smoothed. The lane's five-organ United States sum for 2024 is 48,837, but the same report states 46,750 total solid-organ transplants for 2024, and a sum of five organ categories cannot exceed the all-organ total. One of the two is counting something different - most likely organs within multi-organ procedures against procedures performed - and the cycle did not resolve which. The 25 percent threshold is therefore recorded as roughly 11,700 to 12,200 organs a year for the United States rather than as a single figure. The United Kingdom result is one country over one year-pair, taken from a charity's summary of the registry rather than from the registry document, whose decade series exists only as chart images that could not be extracted. The Eurotransplant zone yields one clean year: kidney waiting list 10,002 at year-end 2024, against 3,017 deceased-donor kidney-only transplants, with a five-organ deceased-donor total of 7,156 that excludes living donors and is therefore a floor.
The master independently fetched the SRTR 2024 Annual Data Report overview and confirmed the liver, heart, lung and total figures the lane reported, matching them exactly, so the organ-axis result does not rest on lane extraction. The United Kingdom, Eurotransplant and Canada figures were not re-fetched by the master and are reported as the lane returned them, with the lane's own read-status labels preserved: it read the Kidney Research UK page and the CIHI page directly, and extracted the Eurotransplant tables with pdftotext after the fetch layer failed on the PDF.