Bringing organ-scale cryopreservation into existence (Hunter Davis, Until Labs Team)

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This is an interview with @huntercoledavis , the CSO and co-founder (alongside @LauraDeming) of @untillabs, which you may also know by its prior name, Cradle. They are a biotech startup devoted to organ-scale cryopreservation. They raised a $58M Series A back in September 2025, and are backed by Founders Fund (especially interesting!), Lux Ventures, and others.

In this interview, we mainly talk about the engineering and scientific difficulties in the cryopreservation field, including some background details on their September 2024 progress report on neural slice rewarming, how they characterize tissue damage in their attempts to do kidney cryopreservation, the potential economics of future cryopreservation protocols, and lots more. One of the most interesting conversations Iā€™ve had in a long time. If any of this work seems interesting, Until Labs is actively and aggressively hiring! Enjoy!

Full transcript available on the Owl website:

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CGPT5.1 Video Summary:

A. Executive Summary

The conversation begins with the rat-kidney vitrification study: a kidney was removed, loaded with cryoprotectants, vitrified, rewarmed, reimplanted, and ultimately recovered full function over weeks. This confirms that mammalian organs can survive both the cooling/rewarming process and the intermediate biochemical damage (e.g., transient cellular lysis). The interview then examines immune complications: even autologous grafts can provoke immune activation because cryogenic stress exposes intracellular epitopes, a mechanism previously observed in pediatric heart-tissue reimplantation.

Hunter Davis emphasizes how immature the organ-level field remains compared with embryo vitrification (~150,000 vitrified-embryo births per year in the US). He describes his evaluation rubric for cryopreservation papers: (1) organ-viability assays must match clinical standards in the target field (e.g., nephrology for kidneys), and (2) molecular papers must interrogate physical chemistry, especially how cryoprotectants interact with water via hydrogen bonding, Raman spectra, and coordination structure. He details Until Labsā€™ use of molecular dynamics, coexistence simulations, and emerging neural-network potentialsā€”not to perfectly model nucleation (still intractable) but to identify correlates that predict lab performance.

The second half focuses on economics, logistics, and regulatory paths. Organ vitrification reduces reliance on urgent, high-cost logistics (private jets, overnight surgeries), increases usable-organ yield by preventing transit expirations, and enables better immunological matching. Vitrification does not eliminate organ scarcity; it mitigates losses and enables future xenotransplantation, which Davis argues requires cryopreservation to enable ā€œon-demandā€ shelf-stable xenografts.

The discussion concludes with recruiting philosophy (agentic, low-ego, cross-disciplinary thinkers), Davisā€™s motivation (impact + tractability), and the internal bottlenecks: organ-scale preclinical studies and foundational physical chemistry remain the rate-limiting steps.

B. Bullet Summary

  1. A rat kidney has been vitrified, rewarmed, autotransplanted, and restored to full function after several weeks of recovery.
  2. Cryogenic stress can cause limited cellular lysis, exposing intracellular epitopes and provoking immune responsesā€”even in autologous grafts.
  3. Embryo vitrification is the sole cryobiology domain with massive N (~150k live births/year in the US).
  4. Organ-level cryopreservation lacks equivalent empirical depth; best practices are still forming.
  5. High-quality organ papers must use the same viability assays clinicians use (e.g., NMP biomarkers for kidneys, livers, lungs).
  6. At the molecular level, Davis values mechanistic work (e.g., waterā€“DMSO hydrogen-bond structure via Raman spectroscopy) over broad screens.
  7. Until Labs uses coexistence molecular dynamics to measure iceā€“liquid equilibria, not nucleation itself (too rare/fast to simulate).
  8. Neural-network potentials improve realism in modeling hydrogen bonds but remain computationally expensive.
  9. Quantum-mechanical accuracy is required for certain waterā€“CPA interactions that Lennard-Jones potentials cannot capture.
  10. Vitrification suppresses the logistical urgency of current organ procurement, eliminating the need for middle-of-the-night surgeries and private jets.
  11. Current organ loss from transit failures (weather delays, plane de-icing) numbers in the low thousands annually; vitrification could reclaim much of this.
  12. The organ-shortage crisis remains supply-limited even with perfect logistics; vitrification does not ā€œsolveā€ scarcity.
  13. DCD (donation after cardiac death) organs become more viable if ischemic windows can be extended with cryopreservation.
  14. Davis argues xenotransplantation requires vitrification to deliver ER-ready, on-demand hearts and kidneys for acute indications.
  15. Economic model: insurers + Medicaid reimburse transplant centers; vendors (TransMedics, Until) sell devices/services, not organs.
  16. Regulatory pathway likely proceeds via medical-device frameworks, analogous to hypothermic or normothermic perfusion machines.
  17. Recruiting emphasizes agentic, cross-disciplinary thinkers able to design experiments that prove themselves wrong.
  18. Medical expertise is hardest to recruit due to US clinical-practice incentives.
  19. Davis shifted from academia due to impact + tractability: time-shifting disease treatment offers a uniquely large ā€œlever arm.ā€
  20. The largest bottleneck is scaling organ-level preclinical experiments; theory is cheap, organ work is capital-intensive.

D. Claims & Evidence Table

Claim Evidence Provided Assessment
Rat kidneys can be vitrified and function after reimplantation. Describes autologous rat-kidney experiment: vitrified, rewarmed, transplanted, weeks-long recovery to normal function. Strong (consistent with published nanowarming literature).
Cryogenic lysis can provoke immune activation even in autologous grafts. Pediatric heart-tissue reimplantation cases show immune responses despite perfect matching. Moderateā€“strong: mechanism plausible; limited N in cryogenic context.
Embryo vitrification is a mature field (~150k births/year). IVF practice and US birth statistics. Strong; widely documented.
High-quality organ papers must match clinical viability assays. Davis emphasizes nephrology-standard markers, NMP biomarkers. Strong, consistent with transplant-medicine norms.
MD coexistence simulations correlate with experimental performance. Internal empirical correlation from Until Labs. Moderate; correlation ā‰  mechanistic simulation of nucleation.
Ice nucleation is too rare/fast for direct MD simulation. Explains femtosecond time-steps and nanosecond nucleation timescales. Strong; reflects known computational limits.
Neural-network potentials aid in modeling waterā€“CPA interactions. Davis notes improved accuracy for hydrogen bonding. Moderateā€“strong; supported by emerging literature.
Vitrification reduces reliance on private jets and urgent logistics. Current system requires high-cost, time-critical transport; vitrification removes urgency. Strong; logistics constraints are well known in OPOs.
Organ losses from logistics number in the thousands/year. Based on public OPO outcome data and anecdotal de-icing case. Moderate; precise numbers vary; mechanism plausible.
Xenotransplantation requires cryopreservation for full potential. Argument: shelf-stable xenografts unlock acute indications. Speculative but coherent; depends on future xeno viability.

E. Actionable Insights

  1. Organ viability assays must be harmonized with clinical transplant standards (e.g., NMP perfusion metrics) to enable credible translational evidence.
  2. Molecular-level cryoprotectant development should prioritize mechanistic water-interaction data (Raman spectra, hydrogen-bond topology) to enrich in-silico screening.
  3. Coexistence MD simulations + neural-network potentials can serve as an early-stage prioritization filter , even though they cannot model nucleation events.
  4. Engineering solutions should be co-optimized with cryoprotectant chemistry: improved volumetric heating reduces required CPA concentration and toxicity.
  5. Clinical value is front-loaded in logistics: reclaiming lost organs and improving matching yields immediate, high-value outcomes before whole-body applications.
  6. DCD donors are a near-term expansion frontier: extending ischemia tolerance could increase usable organ supply.
  7. For future xeno-organs, vitrified ā€œon-demandā€ stockpiles could reshape ER medicine , shifting transplantation from chronic to acute care.
  8. Recruiting strategy should emphasize agentic generalists with low-ego experimental skepticism , not niche specialists with rigid training.
  9. Accelerating preclinical organ-scale experiments is the binding constraint; capital should be directed to high-throughput organ perfusion + rewarming setups.
  10. Regulatory planning must resemble device pathways, using precedents from hypothermic and normothermic perfusion systems.

H. Technical Deep-Dive

Immune Epitope Exposure Mechanisms

Cryogenic stress induces limited but non-zero cell lysis, exposing intracellular proteins (e.g., actin, nuclear antigens) normally sequestered from immune surveillance. In an autologous context, these can behave like neo-epitopes. Pediatric cardiac reimplantation studies show this mechanism is plausible. Quantifying the threshold of lysis compatible with immune quiescence is an open research gap.

Waterā€“CPA Coordination

Raman spectroscopy and neutron-scattering studies show that CPAs like DMSO reduce tetrahedral water structure, increasing coordination heterogeneity and raising the free-energy barrier for critical nucleus formation. Accurate simulation requires quantum-accurate hydrogen-bond potentials; classical Lennard-Jones models distort coordination geometry. Neural-network potentials (e.g., ANI-style or DeepMD) incorporate short-range QM fidelity but remain computationally expensive.

Nucleation Simulation Challenge

Ice nucleation is a rare-event problem: nucleation times in supercooled water are orders of magnitude longer than MD time windows. Coexistence simulations bypass nucleation by pre-placing an iceā€“liquid interface and measuring extension vs melting. This yields correlative vitrification scores but cannot resolve heterogeneous nucleation sites on proteins, membranes, or vasculatureā€”still the unsolved core of cryobiology.

Organ-Scale Thermal Transport

Livers, kidneys, and hearts have centimeter-scale diffusion paths; conduction-only cooling/rewarming is too slow to avoid passage through growth-favored temperature windows. Volumetric rewarming (e.g., magnetic nanoparticle heating) provides near-isothermal internal heating, reducing spatial dT/dt gradients that otherwise cause crystallization. Vasculature provides natural perfusion pathways for uniform CPA loading and nanoparticle distribution.

Organ-Specific Constraints

Kidneys tolerate ischemia (ā‰ˆ72 h on ice), whereas lungs do not (ā‰ˆ4ā€“6 h). Livers are the most extensively researched organ in perfusion science. Whole-organ vitrification equalizes these disparities by eliminating ischemic clocks, but CPA toxicity, osmotic excursions, and rewarming heterogeneity remain organ-specific challenges.

I. Fact-Check and Evidence Review

Embryo vitrification success: Supported robustly; US data show ~150k vitrified-embryo births/year.

Rat-kidney vitrification: Confirmed via University of Minnesota nanowarming studies.

Cryoprotectant mechanistic literature: Substantial Raman/DSC data on DMSOā€“water interactions.

NMP biomarkers: Well-established predictors of graft viability in transplant literature.

Antifreeze proteinsā€™ temperature limits: Operate near 0 Ā°C; unsuitable for āˆ’130 Ā°C vitrification.

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