Why Cryopreservation is No Longer Science Fiction with Until Co-founder and CEO Laura Deming

What if we could pause biological time to wait for a cure for a disease? Thanks to innovations and research in reversible cryopreservation, this possibility is no longer just science fiction. Sarah Guo sits down with Laura Deming, CEO and co-founder of biotech startup Until, to dive deep into the growing field of reversible cryopreservation. Laura talks about how her time as a Thiel Fellow as well as her founding of the Longevity Fund fueled her obsession with solving the “social blindspot” of aging. Laura details how her new startup, Until, seeks to build tools that allow for “pressing pause” on biological time, starting with human organs with the hopes of scaling up to full body medical hibernation. Together, they also discuss why ice is the enemy of tissue, using engineering tools to help solve biological problems, and how this technology may revolutionize organ transplantation by removing time as a variable. Sign up for new podcasts every week. Email feedback to [email protected] Follow us on Twitter: @NoPriorsPod | @Saranormous | @EladGil | @LauraDeming | @untillabs Chapters: 00:00 – Cold Open 01:08 – Laura Deming Introduction 01:53 – Why Laura Focused on Cryo Preservation and Longevity 06:20 – Bringing on Co-Founder Hunter Davis 07:55 – Until’s Goal 10:10 – Other Use Cases for Cryo Technology 12:22 – Scientific Challenges in Cryo Tech 15:36 – Using Engineering Principles to Solve Biological Problems 20:18 – Scaling Up Cryo Preservation 21:48 – Leading and Recruiting at Until 25:02 – Why Hasn’t Cryo Tech Been Worked On More? 27:14 – Making Time Not a Variable in Organ Transplants 29:06 – Changing How the Molecular World is Depicted 30:47 – Conclusion

• 0:00Speaker 00

  What if you could take someone who is on their deathbed and find some way to hibernate them until the sort of critical cure for their disease comes online?

• 0:08Speaker 01

  The ability to freeze time for humans. I didn't actually think that was something you could go work on. So apparently it is.

• 0:14Speaker 00

  Our long-term goal is reversible whole-body cryopreservation for medical hibernation. But in the near term, what we work on is reversibly cryopreserving single human organs to help transplant patients get organs more efficiently. Making time not a variable changes the whole paradigm. One thing I love about the field of cryopreservation is I think, like, the problem speaks for itself. Water expands when it forms ice. That's just hard for your tissue to take without substantial damage. And the cool thing is that there's sort of a temperature below which ice formation stops happening. So basically, if you can traverse and you can get below that without ice formation, then you're good. We already reversibly cryopreserve tissue, including human tissue, all the time. And we do it for very long time periods. There are kids who were literally cryopreserved for 30 years as tiny embryos. And so the main question is not, is this possible to do at all? It's, is it possible to scale up?

• 0:59Speaker 01

  Given that's true, why don't you think it's been worked on?

• 1:08Speaker 01

  Hi, listeners. Welcome back to No Priors. Today, I'm really excited to be here with Laura Deming, previously the founder of the Longevity Fund, and now the co-founder and CEO of Until. We're going to talk about how Until is progressing the frontier of reversible cryopreservation, or freezing living things and waking them back up, beginning with human organs, progressing to small animals, and hopefully making progress on the whole body. It sounds like science fiction, but we'll talk about some of the scientific challenges, where we are today, and the implications if this is possible. Thanks so much. Welcome, Laura. Laura, thanks so much for doing this.

• 1:45Speaker 00

  Yeah, thanks for having me.

• 1:46Speaker 01

  I've been so looking forward to this since our Pantheon Watch sessions. We're talking about upload and the nature of consciousness. But one thing that you don't know is that my, like, very long ago wished-for technologies that I wanted to exist were telepathy and, like... Upload the ability to freeze time for humans. I didn't actually think that was something you could go work on. So apparently it is. How do you end up working on that or being interested in longevity at all?

• 2:14Speaker 00

  There's two different questions. So I come from longevity background, but in my mind, like reversible cryopreservation is applicable a bit outside of that as well. I don't know. I mean, I think I'm really obsessed with areas that feel like they should be worked on, but aren't. And, you know, when I was a kid, I think naively, just growing up, that seemed really obvious for longevity. And it was really surprising to realize that, you know, it's not the case that most people like are working on that explicitly as a goal. And in fact, that like, it's kind of like, I think longevity and aging can occupy this weird realm where because they're not like explicitly diseases in a way that's fully socially recognized yet. They're not seen as valid to work on, but like, that's not really for, I think, technical reasons on some level.

• 2:56Speaker 00

  It's more for like classification reasons because like, you know, you can't extend the lifespan of like, uh, sort of many different organisms using technology. And how much can you do in humans? We have no idea. And, you know, it could be very small of technology, but sort of like, I think longevity is interesting because it feels like an area where there's a social blind spot around something. And I find those very interesting.

• 3:17Speaker 01

  Perhaps I was just, I'm sure this is true, not very observant as a, you know, school age child. But I don't think I even understood aging was like a concept that I should consider at all. Like, and so how did you end up thinking about it in any depth?

• 3:31Speaker 00

  I grew up in a pretty odd setup. So, you know, I was in New Zealand, I was homeschooled. I didn't really have a, like, I didn't go to a normal biology class. I was kind of, you know, by myself in the house.

• 3:43Speaker 01

  I imagine you like staring at a field of sheep and then being like, someday we're going to get old. I should do something about this.

• 3:50Speaker 00

  Yeah, no, that would have been the farm that we had for a little bit. But I remember one thing that was, that really stood out to me was, um, at some point when I was a kid, I was thinking about how long people in my life were going to live and how old they were. And for some reason, it made a lot of sense to me that everyone should live until they were 10 years old and then die immediately at 10 years old. Like I just, that like, that seemed like some hypothesis. I didn't really know how old people were. And so working backwards, I was like, oh, my dad must be like, you know, maybe eight and my mom's younger than him. So like maybe seven. But I think one thing that was really striking was realizing that we don't all live until a certain age and then we die. In fact, we don't, you know, know. Like what determines how long we live? Like that was very interesting, right? This idea that like, I almost get if we all live until 10 years old and then we died immediately at 10, like I would feel much more confident with the idea that longevity is some kind of inalienable, like hard limit. But the idea that like, there was uncertainty about that.

• 4:35Speaker 00

  It was really interesting and then sort of like, what are the factors behind that uncertainty?

• 4:38Speaker 01

  So I'm gonna fast forward through a bunch of like, lab work you did and going to MIT and being a Thiel fellow, like, why a longevity fund?

• 4:48Speaker 00

  Me just being very literal, like, at the time that I was interested in longevity, I think if you ask the average person in the field, like, what's the big problem? Most people would say, well, we just can't get enough funding for our projects. And so that's the big problem. And I just took that literally, like, when I was a teenager, so I went out.

• 5:03Speaker 01

  I'll solve that problem.

• 5:03Speaker 00

  Yeah, I was literally like, I should just get a lot of money to like, help push longevity drugs forward. And the name for that happened to venture capital fund, but it definitely wasn't working downstream of the idea of venture capital. Like, that came after this idea of like, just getting money for projects that should have money and didn't.

• 5:19Speaker 01

  You did this for a number of years. What triggered the, like, sort of change in how you were gonna spend your attention to cryopreservation?

• 5:26Speaker 00

  I think just like, cryopreservation is one of the coolest, like, I think it's not like, to pardon the pun, but I think it's one of the coolest, most interesting, like, best problems ever. Like, I think, like, I mean, if, from so many different angles, like, I think you have such a counterfactual impact. Like, if you're obsessed with, like, just technical delight, like, just rush your, like, technical interest and diversity and, like, a lot of technical parts of the problem. And then also, I think from perspective of social impact, like, I'm just, it was just, it's such an interesting problem from like, how it's perceived and then like, what are the different factors of that? It was like zero to one. It was like the, I remember just seeing the problem clearly for the first time. I mean, a lot of the people in my life, I think, had been aware of it, but I just, it took me so long to really, I think, see it clearly for myself. But then it was just like zero to one of like, this is the only thing that I could

• 6:10Speaker 00

  imagine, pouring the next decade of, like, my work into. That was after I kind of done, kind of, the first set of work with the fund, I was kind of like, thinking about like, what is the next, like, big thing?

• 6:20Speaker 01

  With your co-founder Hunter, was it like, an immediately obvious, yes, we should work on this together?

• 6:26Speaker 00

  He's one of the few people where if I ask him a question, like he'll come back the next day and give me an answer where he's literally thought through from first principles, like what the correct answer is. Like, I remember at some point, I realized that he'd written a doc on like the principles of like, you know, cryopreservation. Like, most people, you know, like, like would write that from the literature or kind of like citing different sort of sources at various levels of granularity. Hunter went back and like re-derived fundamental laws of stat mech as a part of like, this is what you should know in cryopreservation doc. Like, I really admire how much he builds up from like, like, like really simple models to try to create coherent like technical pictures that are more complex. He's like the most fun, interesting, best person to work with, ever, for sure.

• 7:07Speaker 01

  And it wasn't a hard sell, like, we should go work on this problem in particular.

• 7:11Speaker 00

  It was not a hard sell, but it was not an interesting way. So I think one thing that I like, love about the field of cryopreservation is I think it's very compelling. Like, if you like, it's one of those things where if you, like, the problem speaks for itself. And so I remember telling Hunter about it in our first call, and he basically was like, "Oh, I don't buy it." He told me later that he didn't tell me in the call. But then he went off and thought about it for a couple of days and like, really thought about like, what we knew about ice formation, like, did, you know, some like, basic back of the envelope math, and came back and he was like, "Oh, wait, this seems like actually, or like, this seems like it's in the realm of possibility in a way that is very different from my initial intuition." And that, that sort of like conjugation is just so interesting to me.

• 7:55Speaker 01

  Maybe it's useful to zoom out and just say, like, what is the goal of Until?

• 7:58Speaker 00

  I would think about our goal as trying to create a new form of critical care. The example that I would give that is sort of the core of the company is, there are some years where certain diseases such as like metastatic melanoma go from being, like, like, sort of, in a single year, like metastatic melanoma went from being something that you had like a six to nine month prognosis, like less than a year of expected survival, to with like, you know, new combination immunotherapies, you might have a decade plus of expected survival, or like 50% of people sort of surviving over a decade, you know, without getting sort of death from melanoma. In fact, there was starting to have other things at that point. The tagline is like, "Single years can make the difference between a patient dying of internal illness and like, living long enough to make the critical cure." But right now, like, there's no way to press pause on their biological time.

• 8:43Speaker 00

  Like, what if you had an ambulance to the future, right? Like, what if you could take someone who is on their deathbed and, you know, find some way to, you know, just sort of hibernate them, basically, until the sort of critical cure for their disease comes online? And like, you know, and in this context, we're not talking about necessarily decades, or kind of like, you know, much longer than that. Initially, it's just kind of in the context of like, when there's a window where you could, you could imagine like, a critical trial is being done for a drug that were they eligible for, it could make a huge difference for their disease. To give an example of like, the need to, it's like, my sort of co-founder's father-in-law, had this happen to him in the sense that he got a sort of advanced cancer that that would have been treated or treatable or addressable by a therapy that came out, basically a couple of months after

• 9:27Speaker 00

  he was no longer eligible for the therapy. And he like missed, you know, the critical clinical trial by like, you know, a couple of months. And so it's sort of like that level of urgency that like someone in that position shouldn't have to, you know, miss a critical therapy because there's a couple of month difference in like when they got their sort of disease and when the therapy came available.

• 9:47Speaker 01

  And from a just like product perspective, that means you need to do whole body cryopreservation?

• 9:54Speaker 00

  Yeah, so, so like, to give context on technically how we think about this problem. So our, our long-term goal is reversible whole body cryopreservation for, you know, medical sort of hibernation. But in the near term, what we work on is reversibly cryopreserving human, single human organs to help transplant patients get organs more efficiently.

• 10:10Speaker 01

  I want to come back to like, all of the technical challenges here and where we are and what you think the next milestones are. But because you, you describe it in the context of medical use, like, I'm going to be honest, as a kid, I was like, well, I want to be able to freeze time because I want to be able to go to Mars, too. Or you said, because you've worked on longevity with this perspective, like aging is, you know, it could be considered a disease, a health state we should work on that is credible medical science. So how do you think about those other use cases?

• 10:39Speaker 00

  So an interesting thing when you start to think about,

• 10:43Speaker 00

  Like actually applying this technology is sort of what's the experience of the person, not just kind of technically for the disease, but socially. So like, like one of the number one reasons most people wouldn't do medical hibernation, and especially that it wouldn't be like for the most part recreational thing is that, you know, you, I think a lot of people view themselves in part defined by their social context. So like.

• 10:59Speaker 01

  And when you say recreational thing, you mean because like you, you just, you think of that as going to Mars as a recreational use case?

• 11:07Speaker 00

  Oh, no, sorry. I, I think this case, what I'm thinking of is, you know, some people might imagine that they would love to skip into the future just to see what happens, you know, and maybe, you know, like have their same amount of number of years of life, but like have the future shifted by some amount of time.

• 11:20Speaker 01

  Yes.

• 11:21Speaker 00

  But the number one reason that most people wouldn't do that and are also just, you know, very wary of the idea of hibernation for themselves is, you know.

• 11:28Speaker 01

  I can't take everybody with me.

• 11:29Speaker 00

  Yeah, exactly. It's a city that like you kind of find yourself by the people around you. And so I think, I think like, you know, those kinds of use cases, like going to Mars are like, those are all kind of things that could happen and could happen with or like sort of could happen, will require hibernation technology for certain like definitions of mind. But I think the thing that a lot of people will face is just like this question of like, is it worth, you know, traveling so far to give up my current social context? And that will put a limit on like how much people want to use this for like, I think there's like a real cost that that kind of you incur. And so it's in my mind, it only makes sense for like really serious use cases initially, where like you literally would die or like, you know, because yeah, because you're kind of putting on the line, like your current, like all of your current social reality and like how that will evolve without you versus like, you know, this other thing that you might want. But I mean, a lot of people might want to go to Mars, you know, that context, because I think I'm a little, yeah, the cost is pretty significant.

• 12:14Speaker 01

  It's very hard to know what we want, though. Like, a lot of people might make that decision whether or not, you know, their ultimate happiness is higher.

• 12:21Speaker 00

  That's fair.

• 12:22Speaker 01

  Maybe you can just break down how you think about the challenges scientifically, right? Versus, I think to maybe even Hunter's original reaction, like, sounds like science fiction. I don't know if you can go work on that thing.

• 12:34Speaker 00

  Yeah.

• 12:35Speaker 01

  Right? And so if it's, you know, crystal formation or whatever the set of challenges and what sequence you think you should solve them.

• 12:43Speaker 00

  I see. Yeah. Maybe I can just give a series of facts that I think.

• 12:50Speaker 00

  Together, sort of make the problem super interesting. So one fact is that ice formation is a stochastic process. So if ice just formed unilaterally in any given material past a certain point of temperature, like, you know, just like go from zero to one, it's like 100% ice. Like, that might be kind of hard to think carefully about technically. But ice sort of forms through a process of random nucleation and then extension. And this is cool because you can modulate the like, sort of nucleation, the rate of nucleation and extension to then modulate the probability of ice formation. And because it's probabilistic, if you can do that well enough and you can sort of spend minimal time in the temperature range where ice can nucleate, then that gives you a shot

• 13:35Speaker 00

  at sort of preventing a lot of ice formation. So like, the number one tagline would be like, avoid ice at all, or like, sort of avoid as much as possible. There may be some, like, I think some people might be working on technologies to cry preserve with some sort of like ice formation, but we're focused on regimes where you're basically trying to avoid as much ice formation as possible.

• 13:51Speaker 01

  Just for the non-biologists, you know, ice formation is bad because it breaks all the cell membranes.

• 13:55Speaker 00

  Yeah, so ice formation is bad because ice expands, water expands when it forms ice, and that's just hard for your tissue to take without substantial damage. So you want to avoid ice formation. And the cool thing is that there's a, there's sort of a temperature below which ice formation stops happening. So basically, if you can traverse, let's say, you know, going below 30 degrees or less, through to around minus 130, and you can get below that without ice formation, then you're good. And the interesting is, is at that point, you're good for quite a long time. So there have been human embryos that were reversibly cry, that were, you know, cry preserved for, the latest record was over 30 years, and then rewarmed and sort of viably used to create pregnancy.

• 14:40Speaker 00

  And then, you know, sort of like, there are kids who were literally cry preserved for 30 years as tiny embryos. And so that's the last thing, which was very surprising to me, which is that, like, we already reversibly cry preserved tissue, including human tissue, including cold body human tissue at that very, very small, like, you know, in a couple hundred cells stage. All the time and we do it for very long time periods, which I honestly like would have first principles been stuck on, is this possible to do it all? It's a possible scale up to a large, complex biological system that has a lot of vascular structure, where you're dealing with different material properties, where you have to think a lot about like perfusion and how to sort of diffuse chemicals in and out and how to like get heat in and out quickly enough. So the idea that you could pause all molecular motion and then randomly restarted and even a cell would survive that, you know, like from first principles to me used to seem crazy.

• 15:25Speaker 01

  But we know that works.

• 15:26Speaker 00

  Yeah, it's like, we just, we already like, so I just, just tried it and it worked. And so now the problem is like scaling that up and doing it in a way that's compatible with like, you know, tissue health.

• 15:35Speaker 01

  Yes, I think one of the things that was most wildly surprising to me, like being in your lab a little while ago is how much it looks like people were working on what I'd consider to be like engineering problems around. It's like, oh, how do we get something to warm quickly and safely enough versus let me go work on this therapeutic?

• 15:55Speaker 00

  Yeah. So, so, so actually I feel like there's this part of the problem that I've been trying to explain externally for a long time. Every time I try to explain it, I think it comes off as like not specific or something, but it is actually one of the core reasons why I think the problem is interesting to work on, which is that like you can trade off like engineering difficulty and biological difficulty to a non-zero degree, like not 100%. You can't just use engineering to solve the problem. You absolutely have biological questions and like those questions could come out in the negative for some of these cases. So like that's not saying you can just make an engineering problem, but like you can make your life easier on the biology front by building better engineering tooling. And the fact that that's possible is a huge deal. Like that is, that is not true for most problems in biology and it gives you a lot of leverage on the problem. This is probably

• 16:40Speaker 00

  interesting to maybe only like 5% of people watching this, but like I, I think that I'm obsessed with is just the idea like temperature is such a beautiful conceptual tool, right? It's like temperature as an idea, something that in physics took like took physics hundreds of years to come up with. It links like molecular motion to a high, like a single high level measurable parameter. And just tuning temperature like sort of tells you about almost like the roles of passive time of like molecules at the nanoscale. Like that's, that's a highly non-trivial sort of conceptual lever to have. Have on a problem. And in biology, one of the biggest problems is like it's really hard to find powerful conceptual levers on sort of like for like nano scale for for manipulating like the nano scale that have anything approaching that degree of sort of leverage.

• 17:23Speaker 00

  Basically, what that gives you is like you can apply a lot of theoretical sort of a lot of theoretical tool kit used in physics to model parts of this question in ways that are actually useful. And it is just not true that you can use like equations from physics to think usefully about almost any other problem in biology. There are publications like the and the context of like medical devices, but like in a in a context where you're talking about like changing the course of terminal illness, which this one is interesting because this doesn't mean that it'll change it, but like it gives you the possibility of some more time. I think it's one of the most important things to understand about the problem. I don't yet understand how to explain it in a way that is clear. But I think it's like one of the most important things to understand about the problem.

• 18:05Speaker 01

  Yeah, maybe if I think about actually applying it like just very concretely to what you are doing, like if it is challenging from a, you know, organ preservation biology perspective to have a organ reheated or sorry rewarmed like evenly throughout, then maybe the thing to do is to like change the surface area to volume ratio of like your heating device or distribute the heat in different ways without like changing your understanding of the biology, but just with new devices and technologies that you invent from the engineering perspective. Like that actually seems like a very simple example. I realize you're implying a like more fundamental view of like why temperature is just such a interesting framework to be working on from

• 18:50Speaker 01

  both an engineering perspective and a biology perspective. And there's like trade offs where you put your effort here. But I think that's actually that's something that like didn't did not occur to me at all coming into your lab and learning more about until I was like, oh, it's actually like a to some degree much simpler problem than I understood to the point of like, well, if you can just reduce and preserve reduce and increase temperature in these ways that are perfect through this organ is going to work. Right?

• 19:20Speaker 00

  Yeah, so I, uh, let me restate that and then give one caveat just to make sure that, like I, uh, can you correctly? So a way that you can talk about the trade-off between engineering and biology is that like with engineering, you can modulate cooling and rewarming rate, just to some, to certain extents. And then that can then change like how much, uh, what we call a cooperative agent or kind of chemical that, um, modulates ice formation, you add to the system. And you want to minimize the concentration of that cooperative agent.

• 19:48Speaker 01

  Basically, it can be toxic.

• 19:50Speaker 00

  Exactly.

• 19:50Speaker 01

  Yeah.

• 19:50Speaker 00

  And so as you increase cooling and rewarming rate, AKA spending therefore minimal time in kind of the dangerous zone of ice formation, you can correspondingly decrease the concentration of cooperative that you're putting in. But if you could instantaneously cool and re-warm, then you wouldn't have to put any CPA in, but that's, that's not something that, uh, we're default assuming is feasible for a, a large system. Um, so there, there's still always going to be a component of biology, AKA like how tissue responds, especially from a toxicity perspective to like a new chemical agent.

• 20:18Speaker 01

  Where are you now in this progression? Like, should I think of it as like, there's a kidney and then it seems like quite a large jump to a small animal, but maybe it's not?

• 20:29Speaker 00

  Yeah, so we work on the two in parallel. So we both work on scaling up cry preservation and rewarming technologies to a kind of human organ scale. And also in parallel, we work on a sort of whole rat reversible hibernation, uh, and translating technologies over, um, from sort of, um, what we learned on the kidney side into, into the rat context, as well as doing things specifically for, for rat.

• 20:53Speaker 01

  When you started the company, did you have a timeline in your own mind?

• 20:55Speaker 00

  Uh, so I, I think initially I was like, we could maybe make some progress and hopefully make some good products, but like the idea of full body cry preservation felt like that would be really far out if that was possible. I mean, I, I think it, I, I definitely still wouldn't put like a near-term timeline on it, but it, I feel like we have a much clearer roadmap, at least to get, to begin to get there. And the first steps seem faster than, than I would have imagined, um, if that makes sense. Like, but, but the, the big unknown to get to full body reversible is the brain. It's unclear, like, like the brain can withstand a lot of change and does withstand a lot of different types of damage or, or change with age, for example.

• 21:36Speaker 00

  But it's unclear whether, like what kind of injury the brain could sustain in the context of like a whole body reversible preservation protocol. And then like what level of fidelity it's possible to do. So like that, that, that to be clear is a big unknown on the neuroscience side. How do you recruit?

• 21:49Speaker 01

  And like lead in a company that has like, let's say, an unclear like timeline around a really big scientific goal like that, like in terms of both finding people that are the right fit, motivating them, and how do you think about urgency in that context?

• 22:04Speaker 00

  I mean, I think we have a pretty clear timeline for our first product, which is like get irreversibly cryopreserved. So basically transplant patients today surprisingly frequently miss organs that are on route to them because there's a timing problem. So like, you know, organs expire very quickly after they become available from a donor.

• 22:22Speaker 01

  That's very unfortunate.

• 22:24Speaker 00

  Yeah. And it's crazy because it's like they're the, they're like one of the most precious resources we know of. And yet, like, people regularly charter private jets, you know, like it's like you're pretty much surgeon on a private jet to go pick up an organ, get it back to the patient in time. And you're doing all of that at the last minute and scheduling the patient for surgery at the last minute. So the patient has to wait within like a two hour radius of a transplant center with a pager on them or like a notification device at all times. And so the first product that we're aiming towards is just, you know, being able to pause time for the organs. The patient doesn't, you know, you can take as long as you need to get the organ for the patient. And that's very near term. Like that's not long-term ethical. That's like, we're aiming to get that into like preclinical studies and into the clinic as quickly as possible. So I think it helps to have a very concrete goal that clearly is relevant to our long-term goal, right? I think another thing that was inspiring just about that product was like, if we're

• 23:07Speaker 00

  at all talking about whole body reversible cryopreservation, and we can't make a dent on that problem, like.

• 23:12Speaker 01

  There's no version of not going through it. Yeah.

• 23:14Speaker 00

  It's sort of the same as where like, it's like, if you're serious, that should be doable. And if like, you can't do that, then like, you're not the company to like, do the long-term thing. So that was nice for us to like, have a very clear benchmark for ourselves of like, you know, are we correct that this is attractable technology on that scale?

• 23:28Speaker 01

  I guess, like, is it, is it a challenge or to lead beyond that? Because everybody understands the company has a broader mission? Or is it just focus on step one?

• 23:37Speaker 00

  I think, I think there, there's the possibility that's difficult, but I think right now I feel good about sort of our ability to compete around that, which is like, I think if we were like, it's 100% possible to do whole body reversible cryopreservation, there's no question, we're certain, like, then we would just be bullshitters. And then we, like, we wouldn't be able to recruit because it's, you know, there's a lot of technical risk and there's a lot of uncertainty between here and there. But I think what we can't accurately expose the models that we use to think about the problem, you know, like, why, why we think that this is at all, like, possibly in scope, and like, you know, what we're testing to, you know, sort of trying to get closer to there. And I think the problem is, interesting enough, that, you know, some of the hunter, it's sort of like, really good people tend to be skeptical at first because there's an intuition that it shouldn't work. But then like, they'll see a lot of data very

• 24:20Speaker 00

  quickly where it's like, wait, I wouldn't have thought that was possible intuitively, but that seems to be possible. And so like, let me think about some reverse principles.

• 24:26Speaker 01

  What's another data point that you think matters besides like embryos can be frozen?

• 24:31Speaker 00

  Embryos can be reversibly cryopreserved. And there's work from the existing cryopology community, so from John Bishaw's group, and then predated by that also, you know, Greg Fahey has done excellent work, sort of looking at reversible cryopreservation in kidneys and showing like you can reversible cryopreserve a kidney, re-warm it, put it into a rat that does not have another kidney, and that rat returns normal function after about a month. So it's sort of like, you know, even just on the whole mammalian organ scale, like, this is not a problem that's entirely out in the wilderness, it's something that like, is even academically tractable right now.

• 25:01Speaker 01

  Given that's true, why don't you think it's been worked on? I realize I'm asking an answer for other people, but I'm like, well, that's very odd.

• 25:08Speaker 00

  Yeah, I mean, I think even the field of like, organ reversible cryopreservation really had trouble for a while attracting the resources that would be required to scale it. And I really give a lot of credit to the field pioneers, like, you know, Greg, you know, is this incredible example of somebody who fought tirelessly to make this field a reality and sort of make vitrification a thing that people were taking seriously. And, you know, like, through a long period where I think it just wasn't kind of something to focus on. But I don't know how to put it, but like, in venture, like, I think my whole, my whole job, sort of, in that part of my life is like, picking trends that like, sort of feel like, oh, this, this thing is, just feels weird, or it seems kind of hard to think about, but technically, like, there's nothing kind of that corresponds to that. And I think, like, for example, like, whole body reversible cryopreservation, like, now

• 25:53Speaker 00

  seen as just much more kind of reasonable, but whole body reversible cryopreservation, definitely an area where I think there's just like, so much possibility for conflation with like, really extreme, like, it's, it's, it's hard to talk about it rationally. People either like, love it and they love it so much that they won't question it, or it's like, they're worried that thinking about, that associating with it is a little bit too science fiction for kind of where it might be optimal for them to be focused. And so I think like, I'm kind of dancing around some things that like, are still a bit anti-mammatic around it, but yeah.

• 26:23Speaker 01

  The, the study of longevity has become much more mainstream over the last.

• 26:29Speaker 01

  Five years or so, both academically and in terms of consumer interest. Right. And I think those two things are linked. Do you hope that happens with cryopreservation?

• 26:41Speaker 00

  Aging becoming something that like a one of the best, like someone who seems one of the best, like next generation professors chooses to work on without shame or fear of like not getting grant is great. That part of aging and being on stream is great. And like, I definitely hope that that happens for cryopreservation, specifically also for cryopreservation of like variety of tissues, including like neural tissue and including like things related to whole body work, not exclusively, but like basically that those topics are like seen as something that you're like, it's fine to work on.

• 27:14Speaker 01

  Maybe just like if you go to paint a picture of organ transplantation is transformed by, until like, in what ways? Like, how do you think that will change? Either what type of care patients can receive, or even do you think that has any impact on how people think about the the speed of medical research?

• 27:38Speaker 00

  I think the thing that feels the most compelling for me is just like the experience of the transplant patient. It's really, I think, constricting. It's like you're waiting for a life-changing surgery and you have no idea when it will even be scheduled, you know, and you can't go on vacation or really leave like, and you have to like move, you have to be like close to the place where you will get surgery and you can't leave a certain radius of like travel distance to that place for fear of losing out on your life-changing surgery. Like, that is such a

• 28:06Speaker 01

  And surgery center house arrest.

• 28:07Speaker 00

  Yeah, that's such a crazy proposition. And then I also think, you know, right now for matching, it's like everything's done at literally the last minute. It's like someone dies and organ comes available. And like, you're just kind of calling around, trying to find like what patient is available to get this organ. And you don't have that much time to make the optimal match, right? Sort of like, like who can get to the hospital?

• 28:25Speaker 01

  Yeah.

• 28:26Speaker 00

  Who's on the wings?

• 28:26Speaker 01

  Yikes.

• 28:27Speaker 00

  And so I think just like one sort of transplant surgeon that we've been working with, the way he described it was just like, just making time not a variable changes the whole paradigm. I don't think that will happen overnight, obviously, but like, I think the dream would be that like, everyone in the ecosystem has the time they need to like, you know, make the best possible decisions, sort of like do things in a way that feels the best for them. Like, a surgeon doesn't have to stay up overnight, the same day that they flew out to get the organ to do this, the surgery, you know, they can like, Wait sort of until it's like the best time for them instead of doing it like literally, you know, like as soon as they land, like they go into operation like that. That it just, it's sort of something that when you really think about it, it's like, it's amazing that, I mean, it's incredible that like, everyone is operating this way right now.

• 29:06Speaker 01

  Maybe to close up, if we broaden the scope a little bit, are there other problems that are in, let's say, biology, medicine, science, technology that you think are like worth working on and interesting and perhaps feasible, but people are not looking at as much as they should be? You know, maybe not even making a value judgment, but that you're curious about?

• 29:28Speaker 00

  Aesthetically, I'm just really curious about like how to represent the molecular world in a way that people can understand and engage with. Like, I think it's just such a cool and beautiful thing. It's like, you know, we're talking about kindergarten like roles earlier. It's like this beautiful kindergarten like feels in my mind, very colorful, even though it's like not literally, sort of place to play around. And I think most people experience it as like flat triangles and squares in a biology textbook where it's like, you know, there's an arrow between like this triangle and this triangle. It's just like, doesn't make any conceptual sense and is like confusing and annoying. And so I'm just like, I personally am really curious about like how to represent the molecular world in a way that is really compelling and feels super exciting.

• 29:58Speaker 01

  From an education perspective?

• 30:00Speaker 00

  I think it is artistically cool if it's educational, but I think it's more just because I think it's so beautiful. It's like if you've never seen a tree, it's like, being able to see a tree, it's like, that would be so great, right? You know, it's like this complex fractal thing, and it's like light falling through the sort of tree branches. And I think like the molecular world is like that. It's just, it's a kind of view that's not made accessible to most people. It's hard to conceptualize. You have to like do some amount of studying to sort of like build the world in your mind correctly.

• 30:23Speaker 01

  I look forward to finding that art. Thanks, Laura.

• 30:25Speaker 00

  Thanks for having me.

• 30:29Speaker 01

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