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Close to the Edge Episode 11:
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Close to the Edge Episode 11:
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ALEX PHILIPPIDIS: Howdy, and thanks for taking the time to watch Close to the Edge, the new video series from GEN Edge where we invite leading biotech executives to discuss their science, technology, and their business strategy. I'm Alex Philippidis, Senior Business Editor with GEN-- Genetic Engineering and Biotechnology News-- the publication covering the biotech industry for 40 years.
KEVIN DAVIES: And I'm Kevin Davies, Executive Editor of The CRISPR Journal and GEN Biotechnology-- GEN's new marquee peer-reviewed journal launching early 2022. More details at genbiotechjournal.com.
ALEX PHILIPPIDIS: Close to the Edge is the flagship video of GEN Edge, our new premium subscription channel from GEN providing in-depth exclusive news, interviews, and analysis of key trends in the biotech industry, coupled with a range of multimedia offerings such as this one. More details of our free trial offer are at www.genengnews.com/genedge.
KEVIN DAVIES: Most of our guests on Close to the Edge are biotech CEOs, but we're making a slight exception here on episode 11. Not so much a biotech CEO as a world-renowned researcher and serial entrepreneur who seems to spin off a new biotech company about once every few weeks, or so it seems from the headlines. For nearly four decades, George Church, Professor of Genetics at Harvard Medical School, has been at the forefront of countless fields, including genomics, gene editing, organoids, synthetic biology, de-extinction, and I'm sure we'll cover a few others that we've missed in the introduction.
KEVIN DAVIES: So all the way from-- I believe he's at Harvard Medical School today-- George Church. Welcome to Close to the Edge.
GEORGE CHURCH: Oh, it's great to be here. Thank you.
KEVIN DAVIES: Fun to see you again, George. We look forward to a really interesting conversation. Tell us, before we talk about some of your company activities and spin offs, how about giving the audience the current state of the Church Lab at Harvard Medical School-- the scope, and scale? How many folks are currently working in the lab? And what are a few of the fun areas that your lab is focusing on right now?
GEORGE CHURCH: Well, it has fuzzy edges. There are a lot of people who come and go, visiting scientists and so on. Typically, it's less than 80 people these days.
KEVIN DAVIES: So, manageable.
GEORGE CHURCH: Right. But the problem is, a lot of the soft edges are a bunch of young startups that were with postdocs at the helm-- recent ex-postdocs-- and so they expect me to keep mentoring them exactly the way I did before. So it's not quite as small as it used to be, but it's a wonderful community. All the past and present post-docs, they mentor each other and they kind of take care of each other like older siblings.
GEORGE CHURCH: It's just wonderful to watch the camaraderie they have, rather than the kind of cutthroat that you might be in the cartoons.
KEVIN DAVIES: Dare I ask if you have a favorite project in the lab right now?
GEORGE CHURCH: Oh. Well, you probably that we recently got a large SRA sponsored research from two companies. One is involved in gamete production, and the other is working on elephants. So those were things that were very poorly funded before, and so it's interesting to watch that step up. But some of the things that I think are as quirky as those were once not so long ago are things like trying to do 3D printing by using developmental biology methods, rather than using 3D printing to make-- structure organs, used the way that organogenesis goes, but accelerated.
GEORGE CHURCH: So we've accelerated some things almost 100-fold, and we're just beginning to learn the language of morphology.
KEVIN DAVIES: Do you see more of your students-- it sounds like you do-- going into industry compared to maybe 20 or even 10 years ago? It sounds like continuing on the academic path is becoming the exception rather than the rule.
GEORGE CHURCH: That is exactly right, Kevin. I try not to influence it even subtly. But yeah, I think what they do is I see a couple of successes like Francois Vigneault with AbVitro and Juno and Luhan Yang with eGenesis and Qihan, and they just say, oh, I can do that. And then they get help from the older ones, too. So, yeah. So yes, it is the favored path at this point.
GEORGE CHURCH: Typically they get startups for academia around $2 million, and for industry it's more like $40 million. So it's kind of, at least at first, seems like a better deal.
KEVIN DAVIES: Yeah. Do you have some projects in the lab that are going on where you say, this has absolutely zero commercial potential or prospects, but it's still fun and I don't care?
GEORGE CHURCH: Yeah. So mammoths fell in that category.
KEVIN DAVIES: Yeah, it did. Right.
GEORGE CHURCH: I didn't think it was fundable by grants nor by industry, and I was dead wrong. And I'm happy to be wrong in that direction. One that I'm working on now that's kind of quirky is trying to make a nanogram probe that can go interstellar distances. And then at the other end, rather than going fly-by which is the Breakthrough Starshot idea-- flying by at 0.2 times speed of light-- this would actually land and then replicate, unpack, and make some communication device.
GEORGE CHURCH: So obviously, that's hard to see exactly where that goes. But it's part of the same idea of harnessing developmental biology so you can make almost anything that's entirely self-propelled. And this might be useful for, say, mining asteroids-- something much closer to home than the near the nearest star. We're in that kind of zone and colony, and figuring out ways that we could do a better job of colonies for humans.
KEVIN DAVIES: Great, OK. Alex, over to you.
ALEX PHILIPPIDIS: Thanks, Kevin George, if I'm not mistaken, you've co-founded about 20 companies or so. And we'll talk about many--
GEORGE CHURCH: 38.
ALEX PHILIPPIDIS: 38. Wow. OK.
GEORGE CHURCH: I've helped with a few more than that. But those are the three that I'm technically a co-founder on. Yeah.
ALEX PHILIPPIDIS: Wow. What has driven you to create all these new companies?
GEORGE CHURCH: Well, it's changed recently. Initially, it was other principle inv-- other faculty members maybe at other universities and I would co-conspire. Or a VC would say, hey, you're really right for this. And basically, I had to be told what was right in my face. And then later, mostly recently, it's been postdocs who get-- they know where the wind is blowing and they point out to me what's right in front of my face.
GEORGE CHURCH: But that's been even more pleasant. It's really great to watch them mature sort of overnight into being a leader rather than just being an assistant professor. Although, there's nothing wrong with being assistant professor, I should rush to add.
ALEX PHILIPPIDIS: Have you ever contemplated-- I know for a lot of these companies, you're a co-founder. Have you ever thought about being a CEO, or would that not work for you?
GEORGE CHURCH: Well, I suppose I think about it everything briefly. No, I don't think it would work well. I'm just too scattered. I'm too interested in too many things. A CEO really has to focus, and also has to be much better at raising money. [CHUCKLES] I get access to a lot of money, but in spite of myself, basically. Not because I'm good at it.
GEORGE CHURCH: Yeah.
ALEX PHILIPPIDIS: [LAUGHS] Wow. Two of your companies have made news within the past couple of months. You were mentioning elephants and mammoths before. One of those is Colossal Laboratories in Biosciences, launched in September with 15 million in seed funding, another serial entrepreneur, Ben Lamm, as your CEO. And I know Colossal's mission is de-extinction of the woolly mammoth and preservation of endangered Asian elephants, for example, enabling them to withstand Arctic temperatures.
ALEX PHILIPPIDIS: How far has that progressed, and how did that come about?
GEORGE CHURCH: Well, it hadn't progressed very far between 2006 and 2021 until September when we actually got some decent funding. I'm very grateful to Peter Thiel, who gave us roughly $10,000 a year for 10 years. But that's not the sort of thing you can do this kind of challenging project on, but it did keep us thinking about it. But anyway, as of September, we've managed to put together quite an amazing team.
GEORGE CHURCH: But more importantly, all that time when we didn't have money, we were feeding in from adjacent projects. So almost everything we do that has to do with human health related technologies is applicable, particularly multiplexed editing, which we did for transplantation work, where you're making maybe 40 or more edits to a multiplex editing and epigenomic reprogramming where we want to be able to make the egg and sperm and endometrium so we can support embryogenesis.
GEORGE CHURCH: All of that was being funded under genome grants and things like that. So really, it was coming together quite well, along with a couple dozen genomes of elephants, both living and extinct. And a lot of collaborations with ecologists and conservationists groups, like in particular Pleistocene Park. So it really just suddenly coalesced over the last couple of months.
ALEX PHILIPPIDIS: You spoke of multiplex editing. In this case, you have larger mammals. In this case, did that differ? How will that, versus some of the work, say, with the kidney and other organs as in eGenesis?
GEORGE CHURCH: Well, the kidneys that we're using right now are going into or have been for hundreds of days in pre-clinical trials with primates. They're going from pig to primates. So these are relatively large animals that we're dealing with. We also have clinical trials on a veterinary product for aging reversal in dogs. So the elephant is the largest of the animals so far, but it's not exceptional-- truly exceptional.
GEORGE CHURCH: And we think that we've sort of de-risked what we need to do in the elephants considerably via all these other activities in the other animals. And the pigs are the best example because we've got 42 edits. They're viable herds of pigs, a few dozen of them that are actively donating organs in three different hospitals in the United States.
ALEX PHILIPPIDIS: Now, some critics have expressed that this venture is not likely to succeed. Maybe it's too fanciful, or you'll have trouble socializing these gene-edited animals. What do you see as the biggest challenge for this colossal?
GEORGE CHURCH: Well, there are quite a few of them. I think if we do it exactly the way we did the pigs, the gestation period's longer, but it's not infinite. It's 22 months versus close to four months. Size is a little bit bigger, 100 kilogram birth weight, versus a piglet. But I think the socialization, we have some collaborators and precedents for that.
GEORGE CHURCH: There are, unfortunately, a lot of elephant calf orphans because of the poachers. And all of the elephant species, three or four species depending on the account, are endangered. But anyway, so there's experience with how you can raise, how you provide milk. Apparently, large blankets are sufficient to look to them like the belly of a mother.
GEORGE CHURCH: And hopefully, we'll innovate further on this sort of thing. But there are a lot of challenges. There are other challenges having to do with where are the places in the Arctic that have the largest carbon that's at risk-- largest amount? The Arctic overall has a lot more carbon than the tropical rainforest. But we would like to pick places that have the most and have the lowest human population density.
GEORGE CHURCH: So it's a fun project, because you really have to think in a very interdisciplinary way and have to be thoughtful about all of the economic and social consequences.
ALEX PHILIPPIDIS: Another one of your newer co-founded companies, relatively, is GRO Biosciences or GRO Bio for short. GRO Bio just raised $25 million toward developing protein therapeutics using an expanded amino acid alphabet. How will GRO Bio do that?
GEORGE CHURCH: So the thing that I really like about GRO Bio is that it's using the first organism that has a new genetic code. It was a designed genetic code that involved extensive-- we were just speaking about multiplex editing. This is big time. This is not 42 edits, but 321 edits, and we're now preparing one that has 62,000. But anyway, focusing on the one that GRO Bio is using, it allows three clever classes of nonstandard amino acids that give it the ability to have disulfides that are resistant to the reduction that occurs in cytoplasm, has amino acids that are resistant to proteases.
GEORGE CHURCH: And it has amino acids that can mimic the glycans on the surfaces of cells, which are incredibly important at heart to engineer where you want them and what you want them to be. So those are just three categories-- both the innovation of having highly efficient incorporation of non-standard amino acids, because we completely freed up a whole codon out of the 64 codons, but also the innovative chemistry of amino acids and applications.
GEORGE CHURCH: All three of them put together-- Dan Mandell, who has a post on our lab, really revolutionized the concept of biocontainment with these non-standard amino acids, has gone on to do a masterful job at leading this operation at GRO Bio.
ALEX PHILIPPIDIS: I recently interviewed Dan Mandell and Christopher Gregg, chief science officer who both started their research in your lab. How did they and you come to create GRO Bio?
GEORGE CHURCH: Well, I think it's symbolic or representative of many of the now postdoc initiated. We don't rush to do it. We try to incubate them as long as possible inside the lab until we're sure that they're mature enough so that we won't get diluted out immediately by running out of VC money. And so it was quite evident that people were excited about this new strain-- this first recoded strain.
GEORGE CHURCH: And they started looking around for what the best products were. The first thing that we had published on-- the first non-standard amino acid we published on for biocontainment was bipA, and that did not seem like a good starting product. But diselenides that we did in collaboration with Andy Ellington's lab did look like a great initial product.
GEORGE CHURCH: And that was quite enough to get it launched. But it's kind of true, every postdoc has an invention. Not every invention is something we want to immediately launch. We want to at least incubate it, and sometimes, we quite frankly just put it back into the academic hopper for a while longer.
ALEX PHILIPPIDIS: So when you work with former students and research fellows, how much of a special joy is there in that kind of company formation?
GEORGE CHURCH: Oh, it's really-- I've done a lot both ways. But most of the recent ones are done postdoc, because it's easier. It's more fun. I think it's better for them. We're already on the same wavelength. We've both been drinking the same Kool-Aid for several years. And so we can kind of finish each other's sentences but not in a way that's like inbred.
GEORGE CHURCH: It's more like they're going to take these big leaps, and I can follow along with them very easily in a way that it takes a while to build up that kind of trust. And it's just easier to do that in an academic lab, I think, than it is in a startup company. Startup company there's a lot more stress on bottom lines than there is in an academic lab.
ALEX PHILIPPIDIS: Kevin, over to you.
KEVIN DAVIES: Thank you, Alex. We can't have George on the show without spending a little bit of time talking about gene therapy and genome editing. So another recent Church production, I guess, is Dyno Therapeutics, which uses AI to design AAV, Adeno-Associated Viral, vectors for gene therapy. George, why is this technology so needed and so promising?
GEORGE CHURCH: Right. So there's admittedly quite a few ways of delivering genes-- DNAs, RNAs, double-stranded, single-stranded. There are quite a few. AAV has one of the best profiles for low immunoreactivity. It's not zero, but it's very low. It has a small size, which means that it is a little bit better at diffusing and penetrating. That is a downside when it comes to the payload, but it hasn't really been a gigantic problem so far.
GEORGE CHURCH: And it's probably the most advanced in terms of being able to target away from the liver and towards tissues that you care about. So those are some of the reasons. It's one of the most well-studied viruses. But I was shocked to find how few adenoviral sequences already existed when we started to do the machine learning. Machine learning, as you know, is helped by having lots of prior data.
GEORGE CHURCH: And it was also shocking that we found the new gene in such a well-studied, incredibly tiny virus. We weren't looking for it. We were just doing other things. So yeah. That's why we're doing--
KEVIN DAVIES: Is the purpose of the design to increase the tropism for different tissues, different organs?
GEORGE CHURCH: Correct. So you want to even it out, if you want to have homogeneous systemic delivery, or to target it, if you want to, say, conserve, to be able to inject a smaller dose, which can have lower toxicity or it can just be less expensive. So there's motivation to get away with lower dose.
KEVIN DAVIES: AAVs have become, arguably, the workhorse of most gene therapy trials in the clinic, but we do still see reports of adverse events and occasionally some fatalities in clinical trials. So is that an important driver behind this effort?
GEORGE CHURCH: Yes. So we have another technology, which is not a Dyno, that was aimed at innate immunity-- or just a very short 100-mer would be enough to lower that innate immunity. But in terms of humoral and cell mediated immunity, the peptides are the key thing, and Dyno is really good at making large libraries, millions of designed capsids-- so not random mutagenesis but designed capsids.
GEORGE CHURCH: With random mutagenesis, you basically kill the virus on the order of four mutations. But with the machine learning, we can make large libraries, and we can get out to 28, 29 mutations, probably more, without breaking it. So that's an awesome combination of the machine learning with these mega libraries.
KEVIN DAVIES: Right. I want to touch on CRISPR briefly. Just a little over two years ago, George, I was sitting in your office, and we recorded an episode for GuidePost, The CRISPR Journal's podcast series. I think was episode 40, highly recommended. We talked a lot about CRISPR and hereditary genome editing at that point. Of course, one of the big stories in CRISPR was the Nobel Prize last year to Jennifer Doudna and Emmanuelle Charpentier for the genetic scissors, as the committee called it.
KEVIN DAVIES: Do you think the Nobel Prize committee got it right?
GEORGE CHURCH: I was very happy with that. I know both of them well. Jennifer and I have co-founded or worked together on about three or four companies, including Inari, which is agriculture. Yeah, I think it was-- there were even earlier pioneers, and there were definitely people who came after who turned them into technologies.
GEORGE CHURCH: But they were right at the right position, so I'm very happy about that.
KEVIN DAVIES: Yeah. Well, I think probably the first company that you co-founded with Jennifer was Editas.
GEORGE CHURCH: Correct.
KEVIN DAVIES: And it's about seven years ago, I think, if my math is correct. And of course, the progress has been remarkable. CRISPR Therapeutics, Intellia, and most recently Editas announcing-- not yet peer-reviewed-- but announcing some interim clinical results. And I wanted to ask your impressions of those, because it seemed from-- not that they're necessarily the final jury. But the analysts, who commented on these results, didn't seem to be quite as enthusiastic as they were when CRISPR Therapeutics and Intellia published their phase one studies in The New England Journal.
KEVIN DAVIES: This is for early results on a clinical trial for a hereditary form of blindness, that Editas has been pioneering, called Leber congenital amaurosis.
GEORGE CHURCH: LCA10.
KEVIN DAVIES: What was your take on those early results?
GEORGE CHURCH: Well, I have to put in a caveat. I'm not really an active member of the SAP anymore, and so I don't really have much inside information-- which I probably shouldn't share anyway if I did.
KEVIN DAVIES: Yes.
GEORGE CHURCH: I think the LCA10 was-- a lot of these are chosen based on the limitations of CRISPR, which are that it's good at making a mess, of knocking things out. I call it genome vandalism. And so you're looking for something where it might have a deleterious dominant allele that you want to take out, something like that. And LCA10 was one of those. And it was heralded as the first in vivo CRISPR application.
GEORGE CHURCH: And I think it's too early to be drawing fine lines between each of the early entrants. I'm just pleased by how well all three of these companies have done. I'm involved in two of them. And I've sat at tables many times with the three CEOs, and they get along spectacularly. There's no animosity that I can see. The whole patent thing was really quite academic.
GEORGE CHURCH: Literally, it involved academics, and the companies just paid the bills. So it's just a wonderful community. I think their market cap for the three companies is upwards of $12 billion. And they're helping patients. So I think we should celebrate all three of them and any other company that's out there working on gene therapy broadly, not just CRISPR.
KEVIN DAVIES: Yeah, yeah. That said-- and I think you've sort of teed up this next question quite nicely. We've seen in the last few years tremendous progress in complementary forms of genome editing, base editing, prime editing, and just in the last few weeks a wave of preprints about retrons, and integrases, and recombinases, and transposases. So the genome editing toolbox is overflowing now. Do you see, then, interest in and usage of CRISPR-Cas potentially receding as this toolbox becomes ever richer and more useful?
KEVIN DAVIES:
GEORGE CHURCH: Quite likely. There are many things before CRISPR that we're really quite good. We made like 5,000 perfectly precise edited homologous recombinations in mice, prior to CRISPR, using Capecchi and Smithies' methods, for which they rightly got the Nobel Prize as well. And I love the integrases. One of the big unsolved problems has been putting in bigger pieces of DNA.
GEORGE CHURCH: And Tessera, which I'm also involved in, is not only doing that, but they're looking into the human genome for protein enzymes that won't cause an immune response, which CRISPR is definitely a foreign object. So there's all kinds of things we can do better. But I want to quote the founder of the programming language Fortran. He was asked what the programming language of the future would be like.
GEORGE CHURCH: And he says, I don't what it's going to be like, but it was going to be called Fortran. And I think that's kind of happened with CRISPR. We're giving CRISPR credit for all kinds of things that pre-dated it and post-dated it. And that's fine. If the population can relate to a funny name, that's good.
KEVIN DAVIES: Yeah, yeah. Oh, I think they clearly have. So a lot of current interest in genome editing, and writing, and rewriting-- I want to go back-- I can't resist-- to talk about reading DNA for just a minute. 20 years ago, George, I remember it vividly. You and Craig Venter, among others, were really the first people who said, yeah, we've got the Human Genome Project.
KEVIN DAVIES: Great. We need millions more, and so we've got to get the price down-- even as the champagne was still popping. It's been quite a ride. Genome sequencing is now almost ubiquitous, and human genome is readily available for, I think, a few hundred dollars. Do we still need better, faster technologies to sequence DNA?
GEORGE CHURCH: Absolutely. What we also need to use is the technology we have at the price we have. Because right now, we have this ironic situation where we have a really great price of $300, and that is low enough that you should be able to get probably a 8- to 10-fold return on investment just from serious Mendelian diseases alone. That's probably a trillion dollars that you could save if the healthcare business got a little more serious about prevention.
GEORGE CHURCH: Anyway, do we need more? Yes, because in addition to the inherited genome-- which ideally we could get to billions of people-- there is the day-to-day variation in our environment and our body which also has to be read out-- so the epigenetics and the immunome that's happening within our body and then all kinds of pathogens, and commensals, and allergens in our air. So I think what we need is like portable genomes, for one thing, Our cell phone has 1, or 2, or 3 cameras on it.
GEORGE CHURCH: It should have a few chemical sensors, as well-- chemical and genomic sensors. And then a whole new category of sequencing that we need, which would also consume-- it'll make doing eight billion genomes time six billion base pairs look like small potatoes-- is imaging. There's some imaging methods, notably 10x, acquired by company ReadCoor. And Bruker has a Vutara division that's spun off a company called Acuity that my wife has been involved in.
GEORGE CHURCH: There, you can image every pixel. Every voxel in a thick specimen can be turned into a bar code for DNA, RNA, and protein. So just imagine how much sequencing that will consume.
KEVIN DAVIES: Right.
GEORGE CHURCH: Colors are now sequences, right?
KEVIN DAVIES: Right.
GEORGE CHURCH: And we have more or less an infinite number of colors available for identifying DNA, RNA, protein in C2.
KEVIN DAVIES: Excellent. Well, another good segue. Alex, over to you.
ALEX PHILIPPIDIS: OK, thanks, Kevin. And speaking of segues, to Roswell Biotechnologies, where earlier this week you presented at an event hosted by Roswell, for which you're an advisor. Roswell calls itself the molecular electronics company and unveiled a sensor for single molecule detection. And I think that's what you were talking about just now. You have a paper currently under review, as well. What are your hopes for this technology? And even more basically, how does it work?
GEORGE CHURCH: So we have to give credit to Jim Tour, who's one of the co-advisors and pioneers in this field of molecular electronics. What he did was he showed that you could make a single molecule transistor essentially. But then there's a fair amount left of the subsequent developers to make a megapixel array of such molecular transistors, and make them work, and to get the element that is forming the gate.
GEORGE CHURCH: So the way it works is, with any transistor, is you have a source and a drain where the major electrons flow. And then you've got a gate, which is highly leveraged, where a small fraction of the total determines kind of turning on the valve for the flow of electrons. And that gate historically has been another transistor feeding into this transistor. But now we can have a molecule, and it can be, for example, DNA polymerase, or it could be an antibody antigen interaction.
GEORGE CHURCH: Basically, you can have chemical sensors and nucleic acid sequencing all happening on the same platform. And it's just amazing, the way the thing self-assembles. Some of this is also true for nanopores. But this is much more versatile, I think, than anything we've seen in nanopores, because it is entirely in solution. There's no lipid bilayer present.
GEORGE CHURCH: There's a solid phase where you have a sensor that happens real time. And I think it's also much more highly manufacturable. So I think we're going to see a similar growth curve to what happened to Ion Torrents. Also, Barry Merriman and I were involved in both Roswell and Ion Torrents.
ALEX PHILIPPIDIS: Would these sensors be things we would have on our phone someday? Or would we need other types of vehicles for--
GEORGE CHURCH: Absolutely. They're about the same si-- in a megapixel array, they're the same size as your multi-megapixel phone camera arrays. And they're completely water compatible. So we should be monitoring our food, air, and water on a routine basis with these things. I think it's a little hard to imagine, just like for some people it's very hard to imagine having a computer in your pocket.
GEORGE CHURCH: When I used to ask them in the '60s, when I was very infatuated with computers, they thought, completely, I wouldn't even want one even if it did fit in my pocket. And now try to pry it loose out of their hands. Anyway, I think we are in dire need of more awareness of our environments. It's as if we were blind to all the things floating around, all the pathogens, and allergens, and cancers, and so forth that are developing in our body.
GEORGE CHURCH: Just imagine you could see all of those or better yet that you have a device that kind of buries all the details and tells you when something alarming is happening. It's kind of like our cell phones right now. They don't tell you about the atomic clocks and the GPS satellites. They just tell you when to turn right and left. I think that's where we're going to with this-- and sharing it with social networks.
GEORGE CHURCH: So it's not just telling me I shouldn't go into that room full of Ebola. It's telling the whole community that there's something wrong with that room.
ALEX PHILIPPIDIS: Wow. And how far does this go toward delivering on the promise of the $100 genome? You said it was $300 right now.
GEORGE CHURCH: I don't think there really is a magic number. The magic number was probably $1,000 because that was clearly below the point where you should be able to get a high return on your investment. So if you got the insurance companies, health care providers, almost anybody in the health care system to give it away for free-- but not look at it. They don't have to be the bad guys where they're raising your premiums.
GEORGE CHURCH: If they give it away for free, then you will be a better patient. You will be healthier, and then all the health care costs and insurance payouts go down. So the insurance guys could be the good guys at any moment, ever since the $1,000. But I think it'll get down to $100 within probably two years. It could get down there even faster if they were willing to put up with slightly smaller profit margins.
GEORGE CHURCH: And there's a monopolistic thing going on. It's very analogous to what happened with ABI, and IBM, and a lot of other interesting-- AT&T.
ALEX PHILIPPIDIS: Right.
GEORGE CHURCH: Monopolies change, fortunately.
ALEX PHILIPPIDIS: Another of your interest is in aging research, where years ago you'd co-founded Elysium Health, which offers dietary supplements. The military's planning clinical research and anti-aging with another company, as GEN reported in the summer. More recently, Yuri Milner was said to have invested in Altos Labs, which focuses on reprogramming cells in the lab to prolong human life. How close or how far are we to reversing the effects of aging?
GEORGE CHURCH: Yeah. Well, it's an interesting point. I was involved in the Altos, some of the early discussions, and co-authored with David Sinclair some of the aging reversal use of the Yamanaka factors. Shinya Yamanaka got the Nobel Prize for real aging reversal going from, say, 80-year-olds to zero, to embryos. That's a proof of concept that now has been extended to a gene therapy type of scenario in mice.
GEORGE CHURCH: Those factors, they stay in the cell they're delivered to. And so we've put a little more emphasis into delivering factors that diffuse out, that are secreted, that get distributed systemically. So until we've solved the earlier problem we were talking about, good AV delivery, we have this option of delivering imperfectly of the viral delivered messenger nucleic acids but then delivering broadly the secreted proteins.
GEORGE CHURCH: So that was the basis of Rejuvenate Bio-- well, first three papers and then Rejuvenate File. And they're doing it in dogs first, because the aging reversal in dogs-- or any clinical trial is cheaper, faster in dogs. And also, there's a huge outpouring of enthusiasm for end-of-life benefits in dogs.
GEORGE CHURCH: But I like the term aging reversal that you used. I use it a lot myself as a preference over longevity. Some of my colleagues are trying to force the FDA to accept aging and longevity of diseases, which I think they're probably right from a scientific standpoint. But from a bureaucratic standpoint, it's easier just to accept what FDA does very well, which is serious diseases that you already have.
GEORGE CHURCH: It's hard to do long-term preventatives, because you're starting with somebody that's already pretty healthy. And it's much more likely you're going to make them get worse. Also, with aging and longevity, has such scatter in the human population that any two people might differ 30, 40 years of a normal health span. And so that's a very long clinical trial while aging reversal can happen in weeks.
GEORGE CHURCH: Almost every disease is affected by aging, and so any of these serious diseases of aging can be reversed. And then if your drug is working or your gene therapy is working on all of them at once-- it should be if you're getting it to core of aging-- then you can get any one of them approved, and you basically can get all the rest for free. So that's why I'm excited, and I think it's happening very quickly.
GEORGE CHURCH: The whole field of biotech is on an exponential, partly because reading and writing DNA is on an exponential. And any gene therapy that's aimed at a large population has the chance of being a very inexpensive therapy, in contrast to some of the gene therapies which have the dubious honor of being the most expensive therapy in history, like Zolgensma is $2.5 million per dose.
GEORGE CHURCH: You've got the counterpoint, which is AstraZeneca's adenoviral-delivered double-stranded DNA for COVID, which is $4 a dose. That's my kind of gene therapy.
ALEX PHILIPPIDIS: Do I understand, then, that gene therapy would be a preferred or a main modality for carrying out reversal of aging? Or will we see several over time, as we do with a host of other conditions?
GEORGE CHURCH: Yeah, I don't want to be pragmatic or particularly predictive about it. I tend to gravitate towards gene therapy because of the precision with which you can place it. In addition to injecting a particular site, it tends to stay where you put it. It's a smart kind of therapy, and there can be all kinds of nucleic acid and protein tricks that you can play that are not available small molecules.
GEORGE CHURCH: But I wouldn't write out-- I wouldn't say that small molecules should be ignored, by any means. They have all kinds of advantages. I think, whatever we do, it's going to be a poly pharmaceutical, meaning multiple different pathways simultaneously. Because as some of my colleagues have pointed out, if you just get one of the pathways of aging or cancer, you might gain three years on average in the population.
GEORGE CHURCH: You really have to whack all the moles at once to really get the aging reversal that we're looking for.
ALEX PHILIPPIDIS: And, George, a couple of years startups have focused on using blockchain. There's HLTH.network, which says it's created the first global omics data sharing and analytics marketplace. Three years ago, you co-founded Nebula Genomics with the promise of offering lower cost sequencing of data that you can still store securely through blockchain. Now, earlier this year, Nebula was acquired by ProPhase Labs for almost $15 million.
ALEX PHILIPPIDIS: Why was that company sold? And what form will your involvement have going forward?
GEORGE CHURCH: Yeah. You can think of it as a merger, if you want. ProPhase gave Nebula the ability to-- an experience in direct-to-consumer. So that was what the ProPhase side of it is providing-- and larger scale, scaling up faster. The core that Nebula's providing, in addition to the first $300 genome-- Veritas had provided the first $1,000 genome in 2016.
GEORGE CHURCH: But what Nebula is providing with a variety of encryption-related tools-- the blockchain public ledger is an unalterable way tracking all the ways that the data has been shared. But the homomorphic encryption query allows you to ask questions about the data without actually ever decrypting it. So rather than sharing your genome, we're giving your genome away.
GEORGE CHURCH: You retain it. And there's very circumspect and limited kinds of queries that can be made, but nevertheless very powerful. For example, a physician could help diagnose you without ever possessing your genome. And so it's showing attention to one of the things that people list is the reason that they're not taking advantage of this incredibly cost-effective bit of what should be one of the biggest bits of preventative and personalized medicine in history.
GEORGE CHURCH: And people have various reasons. Either they haven't heard of it, or they're worried about the privacy-- worried about insurance companies in some vague sense. Or they just don't think it'll do anything, again, for a variety of reasons. I think the main problem is the 1% problem, which is the same reason that people didn't accept the surgeon general's warnings about cigarettes.
GEORGE CHURCH: And they didn't buckle up even though they had seat belts in the car, and they had a law. They still didn't buckle up. It's because they felt like, well, 99%'s pretty good lottery odds. And it's not on a public health basis. Anyway, I think we mostly got past that with-- and COVID-19, another one. 1%, I'm good with that.
GEORGE CHURCH: But you're not. You are until your loved ones start dropping off.
ALEX PHILIPPIDIS: Yeah. And looking at another startup that you co-founded, eGenesis Bio, which focuses on xenotransplantation, human compatible organs through multiplex gene editing. How did you get interested in xenotransplantation, and what's the company been doing lately?
GEORGE CHURCH: Yeah. So frankly, what happened was I had just been vaguely aware of it for years. It had been pioneers working on it for two decades before I really got involved. And what happened is we made-- or I don't say we made. Enough noise was made about CRISPR that the pioneers in xenotransplantation, who had been kind of circling around one key gene, which was alpha 1-3-galactosyltransferase, which caused a very acute reaction of animal organs-- like in hours, not in months-- just a immediate reaction.
GEORGE CHURCH: They thought, if they could edit that gene, that would be the cool thing. But then they later realized that that wasn't nearly enough. And collectively, everybody had their favorite gene. They invited us to join into the party with CRISPR. And when we counted them all up, there were over 40 genes that we had to edit, which we now have done multiple times, in multiple different strains of pigs, for various reasons-- and did a sibling company in China, in Hangzhou, called Qihan.
GEORGE CHURCH: But China had its own problems with African swine fever virus, which made it harder to do any kind of pig work. But eGenesis-- back at the ranch in Cambridge, Massachusetts, Genesis has done a really great job of producing multiplex or-- it's really a testament to how much multiplexing you can do in the germline and not mess up the organism, because there's dozens of these things that are now in, as I mentioned, pre-clinical trials in three hospitals.
GEORGE CHURCH: That's looking quite good. Hopefully, there'll be clinical trials in humans soon.
ALEX PHILIPPIDIS: And back in April, eGenesis expanded its research with Duke University to include preclinical research of gene edited kidneys implanted in NHPs, Non-Human Primates. Where does that project be-- [INTERPOSING VOICES]
GEORGE CHURCH: And also at Massachusetts General Hospital and a third hospital-- and islet cells heart. So there's quite a few. Almost everything that's currently transplanted human-to-human is probably up for grabs. I can't say too much about those studies. They're looking very promising. Once they get into the one-year range, which some of them have now, then it becomes a matter of tastes.
GEORGE CHURCH: The FDA will approve moving into human clinical trials at that year point. That's been kind of the magic cut off. But you want to make sure that it goes well. Just because you passed that point is not going to be sufficient-- but hopefully very soon.
ALEX PHILIPPIDIS: All right. More broadly, George, do you find it fairly easy to acquire seed funding when you launch a company nowadays? Or are you still having issues with some startups getting off the ground?
GEORGE CHURCH: It's definitely easier. Certainly, the last couple of years, investors have done very well, both with private and public stocks. That helps. Our reputation has gotten better and better as the years go by, which I'm grateful that that's the perception. But there still are little companies, some of my favorites, that spend more time than they should have to-- the CEO spends-- and more and more frequently, CEOs are scientists.
GEORGE CHURCH: So they're spending precious time they could be focusing on science. So it would be nice if it were even a little bit easier. We don't want to make it too easy, just like we don't want the FDA to be too easy, because there will be unfortunate things that happen if there's not some pushback. But yeah, it's better. I'll tell you the real place that the money is needed the most-- at least right now when we're doing well as an industry-- is in the period between the crazy idea and the precede launch-- crazy idea phase, where we're talking about nanopores, where you take some weird technology from neurobiology called a patch clamp, and you put it together with a DNA polymerase [INAUDIBLE]..
GEORGE CHURCH: That's too weird for words. But now it's one of the main ways of doing long-read sequencing and the only portable sequencer. So it's hard to get grant funding for that. It's hard to get philanthropy funding for it. Often, they're quite technical. Unfortunately, they don't share, with science fiction, the easy communication of sci-fi.
GEORGE CHURCH: They have all the disadvantages of sci-fi, that nobody believes them, with all the disadvantages of the highly technical science, that nobody understands them. So that's the valley of death. It's not the valley of death that most people talk about.
ALEX PHILIPPIDIS: Well, summing up, George, you've been on the faculty of Harvard Medical School for more than 30 years. You show absolutely no sign of slowing down. What are your major goals and hopes for the next 5 to 10 years?
GEORGE CHURCH: Oh, I thought you were going to ask about next 200 years-- for my personal lab, next 200 years, yeah. Yeah, I think 5, 10 years is short time with clinical trials, but it's a very long time with innovation. And a lot of these things are happening in parallel. So in the same 5 to 10-- and in fact, we've now seen a clinical trial that only took 11 months, and that's got our salivation going.
GEORGE CHURCH: But I've mentioned, at the beginning, some of the far out things that we're doing. Another one that I didn't mention is recording information in biological systems. We got a lot of attention for recording in vitro a book, my book Regenesis, in digital form and then in DNA form, made 70 billion copies of it.
GEORGE CHURCH: And that launched an industry that is now an international consortium of companies that are doing that. But I think all of that-- and this is a point that I think is an interesting feature, which is that you can write DNA increasingly easily in vivo. So there's no phosphoramidite synthesis or even new enzymatic methods that we and others are working on in vitro.
GEORGE CHURCH: It's not in vitro at all. It's in vivo. And so we've made a mouse that records about a terabyte of information in 30 nanograms of DNA, scattered through its genome, scattered through every one of its cells, as the equivalent of a black box that you have in airplanes for flight recording. But every cell has its experience with respect to developmental biology.
GEORGE CHURCH: And you could also record a growing number of physiological parameters. A group at UC Irvine took a similar-- took our method and extended it considerably to monitor hypoxia. But basically, you can have flight recorders in all your cells. And then you only have to read the ones that went wrong in some way that you can't use normal diagnosis for.
GEORGE CHURCH: So I think that's quirky. But I think that's a little more evident what the path to market might be than, say, interstellar nanogram probe.
KEVIN DAVIES: Thank you very much, George. We have to leave it there unfortunately. We would love to carry on the conversation, but we'll do this another time. Thanks so much to our special guest--
GEORGE CHURCH: Thank you.
KEVIN DAVIES: --George Church for making the time for us today and joining us on Close to the Edge.
GEORGE CHURCH: Absolutely.
ALEX PHILIPPIDIS: Thanks, George. GEN Edge is where biotech gets down to business. You can sign up for a free introductory trial at www.genengnews.com. Close to the Edge is produced by Bobby Grandone. I'm Alex Philippidis thanking you again for taking the time, and we'll see you next time on Close to the Edge. [MUSIC PLAYING]
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ALEX PHILIPPIDIS: Howdy, and thanks for taking the time to watch Close to the Edge, the new video series from GEN Edge where we invite leading biotech executives to discuss their science, technology, and their business strategy. I'm Alex Philippidis, Senior Business Editor with GEN-- Genetic Engineering and Biotechnology News-- the publication covering the biotech industry for 40 years.
KEVIN DAVIES: And I'm Kevin Davies, Executive Editor of The CRISPR Journal and GEN Biotechnology-- GEN's new marquee peer-reviewed journal launching early 2022. More details at genbiotechjournal.com.
ALEX PHILIPPIDIS: Close to the Edge is the flagship video of GEN Edge, our new premium subscription channel from GEN providing in-depth exclusive news, interviews, and analysis of key trends in the biotech industry, coupled with a range of multimedia offerings such as this one. More details of our free trial offer are at www.genengnews.com/genedge.
KEVIN DAVIES: Most of our guests on Close to the Edge are biotech CEOs, but we're making a slight exception here on episode 11. Not so much a biotech CEO as a world-renowned researcher and serial entrepreneur who seems to spin off a new biotech company about once every few weeks, or so it seems from the headlines. For nearly four decades, George Church, Professor of Genetics at Harvard Medical School, has been at the forefront of countless fields, including genomics, gene editing, organoids, synthetic biology, de-extinction, and I'm sure we'll cover a few others that we've missed in the introduction.
KEVIN DAVIES: So all the way from-- I believe he's at Harvard Medical School today-- George Church. Welcome to Close to the Edge.
GEORGE CHURCH: Oh, it's great to be here. Thank you.
KEVIN DAVIES: Fun to see you again, George. We look forward to a really interesting conversation. Tell us, before we talk about some of your company activities and spin offs, how about giving the audience the current state of the Church Lab at Harvard Medical School-- the scope, and scale? How many folks are currently working in the lab? And what are a few of the fun areas that your lab is focusing on right now?
GEORGE CHURCH: Well, it has fuzzy edges. There are a lot of people who come and go, visiting scientists and so on. Typically, it's less than 80 people these days.
KEVIN DAVIES: So, manageable.
GEORGE CHURCH: Right. But the problem is, a lot of the soft edges are a bunch of young startups that were with postdocs at the helm-- recent ex-postdocs-- and so they expect me to keep mentoring them exactly the way I did before. So it's not quite as small as it used to be, but it's a wonderful community. All the past and present post-docs, they mentor each other and they kind of take care of each other like older siblings.
GEORGE CHURCH: It's just wonderful to watch the camaraderie they have, rather than the kind of cutthroat that you might be in the cartoons.
KEVIN DAVIES: Dare I ask if you have a favorite project in the lab right now?
GEORGE CHURCH: Oh. Well, you probably that we recently got a large SRA sponsored research from two companies. One is involved in gamete production, and the other is working on elephants. So those were things that were very poorly funded before, and so it's interesting to watch that step up. But some of the things that I think are as quirky as those were once not so long ago are things like trying to do 3D printing by using developmental biology methods, rather than using 3D printing to make-- structure organs, used the way that organogenesis goes, but accelerated.
GEORGE CHURCH: So we've accelerated some things almost 100-fold, and we're just beginning to learn the language of morphology.
KEVIN DAVIES: Do you see more of your students-- it sounds like you do-- going into industry compared to maybe 20 or even 10 years ago? It sounds like continuing on the academic path is becoming the exception rather than the rule.
GEORGE CHURCH: That is exactly right, Kevin. I try not to influence it even subtly. But yeah, I think what they do is I see a couple of successes like Francois Vigneault with AbVitro and Juno and Luhan Yang with eGenesis and Qihan, and they just say, oh, I can do that. And then they get help from the older ones, too. So, yeah. So yes, it is the favored path at this point.
GEORGE CHURCH: Typically they get startups for academia around $2 million, and for industry it's more like $40 million. So it's kind of, at least at first, seems like a better deal.
KEVIN DAVIES: Yeah. Do you have some projects in the lab that are going on where you say, this has absolutely zero commercial potential or prospects, but it's still fun and I don't care?
GEORGE CHURCH: Yeah. So mammoths fell in that category.
KEVIN DAVIES: Yeah, it did. Right.
GEORGE CHURCH: I didn't think it was fundable by grants nor by industry, and I was dead wrong. And I'm happy to be wrong in that direction. One that I'm working on now that's kind of quirky is trying to make a nanogram probe that can go interstellar distances. And then at the other end, rather than going fly-by which is the Breakthrough Starshot idea-- flying by at 0.2 times speed of light-- this would actually land and then replicate, unpack, and make some communication device.
GEORGE CHURCH: So obviously, that's hard to see exactly where that goes. But it's part of the same idea of harnessing developmental biology so you can make almost anything that's entirely self-propelled. And this might be useful for, say, mining asteroids-- something much closer to home than the near the nearest star. We're in that kind of zone and colony, and figuring out ways that we could do a better job of colonies for humans.
KEVIN DAVIES: Great, OK. Alex, over to you.
ALEX PHILIPPIDIS: Thanks, Kevin George, if I'm not mistaken, you've co-founded about 20 companies or so. And we'll talk about many--
GEORGE CHURCH: 38.
ALEX PHILIPPIDIS: 38. Wow. OK.
GEORGE CHURCH: I've helped with a few more than that. But those are the three that I'm technically a co-founder on. Yeah.
ALEX PHILIPPIDIS: Wow. What has driven you to create all these new companies?
GEORGE CHURCH: Well, it's changed recently. Initially, it was other principle inv-- other faculty members maybe at other universities and I would co-conspire. Or a VC would say, hey, you're really right for this. And basically, I had to be told what was right in my face. And then later, mostly recently, it's been postdocs who get-- they know where the wind is blowing and they point out to me what's right in front of my face.
GEORGE CHURCH: But that's been even more pleasant. It's really great to watch them mature sort of overnight into being a leader rather than just being an assistant professor. Although, there's nothing wrong with being assistant professor, I should rush to add.
ALEX PHILIPPIDIS: Have you ever contemplated-- I know for a lot of these companies, you're a co-founder. Have you ever thought about being a CEO, or would that not work for you?
GEORGE CHURCH: Well, I suppose I think about it everything briefly. No, I don't think it would work well. I'm just too scattered. I'm too interested in too many things. A CEO really has to focus, and also has to be much better at raising money. [CHUCKLES] I get access to a lot of money, but in spite of myself, basically. Not because I'm good at it.
GEORGE CHURCH: Yeah.
ALEX PHILIPPIDIS: [LAUGHS] Wow. Two of your companies have made news within the past couple of months. You were mentioning elephants and mammoths before. One of those is Colossal Laboratories in Biosciences, launched in September with 15 million in seed funding, another serial entrepreneur, Ben Lamm, as your CEO. And I know Colossal's mission is de-extinction of the woolly mammoth and preservation of endangered Asian elephants, for example, enabling them to withstand Arctic temperatures.
ALEX PHILIPPIDIS: How far has that progressed, and how did that come about?
GEORGE CHURCH: Well, it hadn't progressed very far between 2006 and 2021 until September when we actually got some decent funding. I'm very grateful to Peter Thiel, who gave us roughly $10,000 a year for 10 years. But that's not the sort of thing you can do this kind of challenging project on, but it did keep us thinking about it. But anyway, as of September, we've managed to put together quite an amazing team.
GEORGE CHURCH: But more importantly, all that time when we didn't have money, we were feeding in from adjacent projects. So almost everything we do that has to do with human health related technologies is applicable, particularly multiplexed editing, which we did for transplantation work, where you're making maybe 40 or more edits to a multiplex editing and epigenomic reprogramming where we want to be able to make the egg and sperm and endometrium so we can support embryogenesis.
GEORGE CHURCH: All of that was being funded under genome grants and things like that. So really, it was coming together quite well, along with a couple dozen genomes of elephants, both living and extinct. And a lot of collaborations with ecologists and conservationists groups, like in particular Pleistocene Park. So it really just suddenly coalesced over the last couple of months.
ALEX PHILIPPIDIS: You spoke of multiplex editing. In this case, you have larger mammals. In this case, did that differ? How will that, versus some of the work, say, with the kidney and other organs as in eGenesis?
GEORGE CHURCH: Well, the kidneys that we're using right now are going into or have been for hundreds of days in pre-clinical trials with primates. They're going from pig to primates. So these are relatively large animals that we're dealing with. We also have clinical trials on a veterinary product for aging reversal in dogs. So the elephant is the largest of the animals so far, but it's not exceptional-- truly exceptional.
GEORGE CHURCH: And we think that we've sort of de-risked what we need to do in the elephants considerably via all these other activities in the other animals. And the pigs are the best example because we've got 42 edits. They're viable herds of pigs, a few dozen of them that are actively donating organs in three different hospitals in the United States.
ALEX PHILIPPIDIS: Now, some critics have expressed that this venture is not likely to succeed. Maybe it's too fanciful, or you'll have trouble socializing these gene-edited animals. What do you see as the biggest challenge for this colossal?
GEORGE CHURCH: Well, there are quite a few of them. I think if we do it exactly the way we did the pigs, the gestation period's longer, but it's not infinite. It's 22 months versus close to four months. Size is a little bit bigger, 100 kilogram birth weight, versus a piglet. But I think the socialization, we have some collaborators and precedents for that.
GEORGE CHURCH: There are, unfortunately, a lot of elephant calf orphans because of the poachers. And all of the elephant species, three or four species depending on the account, are endangered. But anyway, so there's experience with how you can raise, how you provide milk. Apparently, large blankets are sufficient to look to them like the belly of a mother.
GEORGE CHURCH: And hopefully, we'll innovate further on this sort of thing. But there are a lot of challenges. There are other challenges having to do with where are the places in the Arctic that have the largest carbon that's at risk-- largest amount? The Arctic overall has a lot more carbon than the tropical rainforest. But we would like to pick places that have the most and have the lowest human population density.
GEORGE CHURCH: So it's a fun project, because you really have to think in a very interdisciplinary way and have to be thoughtful about all of the economic and social consequences.
ALEX PHILIPPIDIS: Another one of your newer co-founded companies, relatively, is GRO Biosciences or GRO Bio for short. GRO Bio just raised $25 million toward developing protein therapeutics using an expanded amino acid alphabet. How will GRO Bio do that?
GEORGE CHURCH: So the thing that I really like about GRO Bio is that it's using the first organism that has a new genetic code. It was a designed genetic code that involved extensive-- we were just speaking about multiplex editing. This is big time. This is not 42 edits, but 321 edits, and we're now preparing one that has 62,000. But anyway, focusing on the one that GRO Bio is using, it allows three clever classes of nonstandard amino acids that give it the ability to have disulfides that are resistant to the reduction that occurs in cytoplasm, has amino acids that are resistant to proteases.
GEORGE CHURCH: And it has amino acids that can mimic the glycans on the surfaces of cells, which are incredibly important at heart to engineer where you want them and what you want them to be. So those are just three categories-- both the innovation of having highly efficient incorporation of non-standard amino acids, because we completely freed up a whole codon out of the 64 codons, but also the innovative chemistry of amino acids and applications.
GEORGE CHURCH: All three of them put together-- Dan Mandell, who has a post on our lab, really revolutionized the concept of biocontainment with these non-standard amino acids, has gone on to do a masterful job at leading this operation at GRO Bio.
ALEX PHILIPPIDIS: I recently interviewed Dan Mandell and Christopher Gregg, chief science officer who both started their research in your lab. How did they and you come to create GRO Bio?
GEORGE CHURCH: Well, I think it's symbolic or representative of many of the now postdoc initiated. We don't rush to do it. We try to incubate them as long as possible inside the lab until we're sure that they're mature enough so that we won't get diluted out immediately by running out of VC money. And so it was quite evident that people were excited about this new strain-- this first recoded strain.
GEORGE CHURCH: And they started looking around for what the best products were. The first thing that we had published on-- the first non-standard amino acid we published on for biocontainment was bipA, and that did not seem like a good starting product. But diselenides that we did in collaboration with Andy Ellington's lab did look like a great initial product.
GEORGE CHURCH: And that was quite enough to get it launched. But it's kind of true, every postdoc has an invention. Not every invention is something we want to immediately launch. We want to at least incubate it, and sometimes, we quite frankly just put it back into the academic hopper for a while longer.
ALEX PHILIPPIDIS: So when you work with former students and research fellows, how much of a special joy is there in that kind of company formation?
GEORGE CHURCH: Oh, it's really-- I've done a lot both ways. But most of the recent ones are done postdoc, because it's easier. It's more fun. I think it's better for them. We're already on the same wavelength. We've both been drinking the same Kool-Aid for several years. And so we can kind of finish each other's sentences but not in a way that's like inbred.
GEORGE CHURCH: It's more like they're going to take these big leaps, and I can follow along with them very easily in a way that it takes a while to build up that kind of trust. And it's just easier to do that in an academic lab, I think, than it is in a startup company. Startup company there's a lot more stress on bottom lines than there is in an academic lab.
ALEX PHILIPPIDIS: Kevin, over to you.
KEVIN DAVIES: Thank you, Alex. We can't have George on the show without spending a little bit of time talking about gene therapy and genome editing. So another recent Church production, I guess, is Dyno Therapeutics, which uses AI to design AAV, Adeno-Associated Viral, vectors for gene therapy. George, why is this technology so needed and so promising?
GEORGE CHURCH: Right. So there's admittedly quite a few ways of delivering genes-- DNAs, RNAs, double-stranded, single-stranded. There are quite a few. AAV has one of the best profiles for low immunoreactivity. It's not zero, but it's very low. It has a small size, which means that it is a little bit better at diffusing and penetrating. That is a downside when it comes to the payload, but it hasn't really been a gigantic problem so far.
GEORGE CHURCH: And it's probably the most advanced in terms of being able to target away from the liver and towards tissues that you care about. So those are some of the reasons. It's one of the most well-studied viruses. But I was shocked to find how few adenoviral sequences already existed when we started to do the machine learning. Machine learning, as you know, is helped by having lots of prior data.
GEORGE CHURCH: And it was also shocking that we found the new gene in such a well-studied, incredibly tiny virus. We weren't looking for it. We were just doing other things. So yeah. That's why we're doing--
KEVIN DAVIES: Is the purpose of the design to increase the tropism for different tissues, different organs?
GEORGE CHURCH: Correct. So you want to even it out, if you want to have homogeneous systemic delivery, or to target it, if you want to, say, conserve, to be able to inject a smaller dose, which can have lower toxicity or it can just be less expensive. So there's motivation to get away with lower dose.
KEVIN DAVIES: AAVs have become, arguably, the workhorse of most gene therapy trials in the clinic, but we do still see reports of adverse events and occasionally some fatalities in clinical trials. So is that an important driver behind this effort?
GEORGE CHURCH: Yes. So we have another technology, which is not a Dyno, that was aimed at innate immunity-- or just a very short 100-mer would be enough to lower that innate immunity. But in terms of humoral and cell mediated immunity, the peptides are the key thing, and Dyno is really good at making large libraries, millions of designed capsids-- so not random mutagenesis but designed capsids.
GEORGE CHURCH: With random mutagenesis, you basically kill the virus on the order of four mutations. But with the machine learning, we can make large libraries, and we can get out to 28, 29 mutations, probably more, without breaking it. So that's an awesome combination of the machine learning with these mega libraries.
KEVIN DAVIES: Right. I want to touch on CRISPR briefly. Just a little over two years ago, George, I was sitting in your office, and we recorded an episode for GuidePost, The CRISPR Journal's podcast series. I think was episode 40, highly recommended. We talked a lot about CRISPR and hereditary genome editing at that point. Of course, one of the big stories in CRISPR was the Nobel Prize last year to Jennifer Doudna and Emmanuelle Charpentier for the genetic scissors, as the committee called it.
KEVIN DAVIES: Do you think the Nobel Prize committee got it right?
GEORGE CHURCH: I was very happy with that. I know both of them well. Jennifer and I have co-founded or worked together on about three or four companies, including Inari, which is agriculture. Yeah, I think it was-- there were even earlier pioneers, and there were definitely people who came after who turned them into technologies.
GEORGE CHURCH: But they were right at the right position, so I'm very happy about that.
KEVIN DAVIES: Yeah. Well, I think probably the first company that you co-founded with Jennifer was Editas.
GEORGE CHURCH: Correct.
KEVIN DAVIES: And it's about seven years ago, I think, if my math is correct. And of course, the progress has been remarkable. CRISPR Therapeutics, Intellia, and most recently Editas announcing-- not yet peer-reviewed-- but announcing some interim clinical results. And I wanted to ask your impressions of those, because it seemed from-- not that they're necessarily the final jury. But the analysts, who commented on these results, didn't seem to be quite as enthusiastic as they were when CRISPR Therapeutics and Intellia published their phase one studies in The New England Journal.
KEVIN DAVIES: This is for early results on a clinical trial for a hereditary form of blindness, that Editas has been pioneering, called Leber congenital amaurosis.
GEORGE CHURCH: LCA10.
KEVIN DAVIES: What was your take on those early results?
GEORGE CHURCH: Well, I have to put in a caveat. I'm not really an active member of the SAP anymore, and so I don't really have much inside information-- which I probably shouldn't share anyway if I did.
KEVIN DAVIES: Yes.
GEORGE CHURCH: I think the LCA10 was-- a lot of these are chosen based on the limitations of CRISPR, which are that it's good at making a mess, of knocking things out. I call it genome vandalism. And so you're looking for something where it might have a deleterious dominant allele that you want to take out, something like that. And LCA10 was one of those. And it was heralded as the first in vivo CRISPR application.
GEORGE CHURCH: And I think it's too early to be drawing fine lines between each of the early entrants. I'm just pleased by how well all three of these companies have done. I'm involved in two of them. And I've sat at tables many times with the three CEOs, and they get along spectacularly. There's no animosity that I can see. The whole patent thing was really quite academic.
GEORGE CHURCH: Literally, it involved academics, and the companies just paid the bills. So it's just a wonderful community. I think their market cap for the three companies is upwards of $12 billion. And they're helping patients. So I think we should celebrate all three of them and any other company that's out there working on gene therapy broadly, not just CRISPR.
KEVIN DAVIES: Yeah, yeah. That said-- and I think you've sort of teed up this next question quite nicely. We've seen in the last few years tremendous progress in complementary forms of genome editing, base editing, prime editing, and just in the last few weeks a wave of preprints about retrons, and integrases, and recombinases, and transposases. So the genome editing toolbox is overflowing now. Do you see, then, interest in and usage of CRISPR-Cas potentially receding as this toolbox becomes ever richer and more useful?
KEVIN DAVIES:
GEORGE CHURCH: Quite likely. There are many things before CRISPR that we're really quite good. We made like 5,000 perfectly precise edited homologous recombinations in mice, prior to CRISPR, using Capecchi and Smithies' methods, for which they rightly got the Nobel Prize as well. And I love the integrases. One of the big unsolved problems has been putting in bigger pieces of DNA.
GEORGE CHURCH: And Tessera, which I'm also involved in, is not only doing that, but they're looking into the human genome for protein enzymes that won't cause an immune response, which CRISPR is definitely a foreign object. So there's all kinds of things we can do better. But I want to quote the founder of the programming language Fortran. He was asked what the programming language of the future would be like.
GEORGE CHURCH: And he says, I don't what it's going to be like, but it was going to be called Fortran. And I think that's kind of happened with CRISPR. We're giving CRISPR credit for all kinds of things that pre-dated it and post-dated it. And that's fine. If the population can relate to a funny name, that's good.
KEVIN DAVIES: Yeah, yeah. Oh, I think they clearly have. So a lot of current interest in genome editing, and writing, and rewriting-- I want to go back-- I can't resist-- to talk about reading DNA for just a minute. 20 years ago, George, I remember it vividly. You and Craig Venter, among others, were really the first people who said, yeah, we've got the Human Genome Project.
KEVIN DAVIES: Great. We need millions more, and so we've got to get the price down-- even as the champagne was still popping. It's been quite a ride. Genome sequencing is now almost ubiquitous, and human genome is readily available for, I think, a few hundred dollars. Do we still need better, faster technologies to sequence DNA?
GEORGE CHURCH: Absolutely. What we also need to use is the technology we have at the price we have. Because right now, we have this ironic situation where we have a really great price of $300, and that is low enough that you should be able to get probably a 8- to 10-fold return on investment just from serious Mendelian diseases alone. That's probably a trillion dollars that you could save if the healthcare business got a little more serious about prevention.
GEORGE CHURCH: Anyway, do we need more? Yes, because in addition to the inherited genome-- which ideally we could get to billions of people-- there is the day-to-day variation in our environment and our body which also has to be read out-- so the epigenetics and the immunome that's happening within our body and then all kinds of pathogens, and commensals, and allergens in our air. So I think what we need is like portable genomes, for one thing, Our cell phone has 1, or 2, or 3 cameras on it.
GEORGE CHURCH: It should have a few chemical sensors, as well-- chemical and genomic sensors. And then a whole new category of sequencing that we need, which would also consume-- it'll make doing eight billion genomes time six billion base pairs look like small potatoes-- is imaging. There's some imaging methods, notably 10x, acquired by company ReadCoor. And Bruker has a Vutara division that's spun off a company called Acuity that my wife has been involved in.
GEORGE CHURCH: There, you can image every pixel. Every voxel in a thick specimen can be turned into a bar code for DNA, RNA, and protein. So just imagine how much sequencing that will consume.
KEVIN DAVIES: Right.
GEORGE CHURCH: Colors are now sequences, right?
KEVIN DAVIES: Right.
GEORGE CHURCH: And we have more or less an infinite number of colors available for identifying DNA, RNA, protein in C2.
KEVIN DAVIES: Excellent. Well, another good segue. Alex, over to you.
ALEX PHILIPPIDIS: OK, thanks, Kevin. And speaking of segues, to Roswell Biotechnologies, where earlier this week you presented at an event hosted by Roswell, for which you're an advisor. Roswell calls itself the molecular electronics company and unveiled a sensor for single molecule detection. And I think that's what you were talking about just now. You have a paper currently under review, as well. What are your hopes for this technology? And even more basically, how does it work?
GEORGE CHURCH: So we have to give credit to Jim Tour, who's one of the co-advisors and pioneers in this field of molecular electronics. What he did was he showed that you could make a single molecule transistor essentially. But then there's a fair amount left of the subsequent developers to make a megapixel array of such molecular transistors, and make them work, and to get the element that is forming the gate.
GEORGE CHURCH: So the way it works is, with any transistor, is you have a source and a drain where the major electrons flow. And then you've got a gate, which is highly leveraged, where a small fraction of the total determines kind of turning on the valve for the flow of electrons. And that gate historically has been another transistor feeding into this transistor. But now we can have a molecule, and it can be, for example, DNA polymerase, or it could be an antibody antigen interaction.
GEORGE CHURCH: Basically, you can have chemical sensors and nucleic acid sequencing all happening on the same platform. And it's just amazing, the way the thing self-assembles. Some of this is also true for nanopores. But this is much more versatile, I think, than anything we've seen in nanopores, because it is entirely in solution. There's no lipid bilayer present.
GEORGE CHURCH: There's a solid phase where you have a sensor that happens real time. And I think it's also much more highly manufacturable. So I think we're going to see a similar growth curve to what happened to Ion Torrents. Also, Barry Merriman and I were involved in both Roswell and Ion Torrents.
ALEX PHILIPPIDIS: Would these sensors be things we would have on our phone someday? Or would we need other types of vehicles for--
GEORGE CHURCH: Absolutely. They're about the same si-- in a megapixel array, they're the same size as your multi-megapixel phone camera arrays. And they're completely water compatible. So we should be monitoring our food, air, and water on a routine basis with these things. I think it's a little hard to imagine, just like for some people it's very hard to imagine having a computer in your pocket.
GEORGE CHURCH: When I used to ask them in the '60s, when I was very infatuated with computers, they thought, completely, I wouldn't even want one even if it did fit in my pocket. And now try to pry it loose out of their hands. Anyway, I think we are in dire need of more awareness of our environments. It's as if we were blind to all the things floating around, all the pathogens, and allergens, and cancers, and so forth that are developing in our body.
GEORGE CHURCH: Just imagine you could see all of those or better yet that you have a device that kind of buries all the details and tells you when something alarming is happening. It's kind of like our cell phones right now. They don't tell you about the atomic clocks and the GPS satellites. They just tell you when to turn right and left. I think that's where we're going to with this-- and sharing it with social networks.
GEORGE CHURCH: So it's not just telling me I shouldn't go into that room full of Ebola. It's telling the whole community that there's something wrong with that room.
ALEX PHILIPPIDIS: Wow. And how far does this go toward delivering on the promise of the $100 genome? You said it was $300 right now.
GEORGE CHURCH: I don't think there really is a magic number. The magic number was probably $1,000 because that was clearly below the point where you should be able to get a high return on your investment. So if you got the insurance companies, health care providers, almost anybody in the health care system to give it away for free-- but not look at it. They don't have to be the bad guys where they're raising your premiums.
GEORGE CHURCH: If they give it away for free, then you will be a better patient. You will be healthier, and then all the health care costs and insurance payouts go down. So the insurance guys could be the good guys at any moment, ever since the $1,000. But I think it'll get down to $100 within probably two years. It could get down there even faster if they were willing to put up with slightly smaller profit margins.
GEORGE CHURCH: And there's a monopolistic thing going on. It's very analogous to what happened with ABI, and IBM, and a lot of other interesting-- AT&T.
ALEX PHILIPPIDIS: Right.
GEORGE CHURCH: Monopolies change, fortunately.
ALEX PHILIPPIDIS: Another of your interest is in aging research, where years ago you'd co-founded Elysium Health, which offers dietary supplements. The military's planning clinical research and anti-aging with another company, as GEN reported in the summer. More recently, Yuri Milner was said to have invested in Altos Labs, which focuses on reprogramming cells in the lab to prolong human life. How close or how far are we to reversing the effects of aging?
GEORGE CHURCH: Yeah. Well, it's an interesting point. I was involved in the Altos, some of the early discussions, and co-authored with David Sinclair some of the aging reversal use of the Yamanaka factors. Shinya Yamanaka got the Nobel Prize for real aging reversal going from, say, 80-year-olds to zero, to embryos. That's a proof of concept that now has been extended to a gene therapy type of scenario in mice.
GEORGE CHURCH: Those factors, they stay in the cell they're delivered to. And so we've put a little more emphasis into delivering factors that diffuse out, that are secreted, that get distributed systemically. So until we've solved the earlier problem we were talking about, good AV delivery, we have this option of delivering imperfectly of the viral delivered messenger nucleic acids but then delivering broadly the secreted proteins.
GEORGE CHURCH: So that was the basis of Rejuvenate Bio-- well, first three papers and then Rejuvenate File. And they're doing it in dogs first, because the aging reversal in dogs-- or any clinical trial is cheaper, faster in dogs. And also, there's a huge outpouring of enthusiasm for end-of-life benefits in dogs.
GEORGE CHURCH: But I like the term aging reversal that you used. I use it a lot myself as a preference over longevity. Some of my colleagues are trying to force the FDA to accept aging and longevity of diseases, which I think they're probably right from a scientific standpoint. But from a bureaucratic standpoint, it's easier just to accept what FDA does very well, which is serious diseases that you already have.
GEORGE CHURCH: It's hard to do long-term preventatives, because you're starting with somebody that's already pretty healthy. And it's much more likely you're going to make them get worse. Also, with aging and longevity, has such scatter in the human population that any two people might differ 30, 40 years of a normal health span. And so that's a very long clinical trial while aging reversal can happen in weeks.
GEORGE CHURCH: Almost every disease is affected by aging, and so any of these serious diseases of aging can be reversed. And then if your drug is working or your gene therapy is working on all of them at once-- it should be if you're getting it to core of aging-- then you can get any one of them approved, and you basically can get all the rest for free. So that's why I'm excited, and I think it's happening very quickly.
GEORGE CHURCH: The whole field of biotech is on an exponential, partly because reading and writing DNA is on an exponential. And any gene therapy that's aimed at a large population has the chance of being a very inexpensive therapy, in contrast to some of the gene therapies which have the dubious honor of being the most expensive therapy in history, like Zolgensma is $2.5 million per dose.
GEORGE CHURCH: You've got the counterpoint, which is AstraZeneca's adenoviral-delivered double-stranded DNA for COVID, which is $4 a dose. That's my kind of gene therapy.
ALEX PHILIPPIDIS: Do I understand, then, that gene therapy would be a preferred or a main modality for carrying out reversal of aging? Or will we see several over time, as we do with a host of other conditions?
GEORGE CHURCH: Yeah, I don't want to be pragmatic or particularly predictive about it. I tend to gravitate towards gene therapy because of the precision with which you can place it. In addition to injecting a particular site, it tends to stay where you put it. It's a smart kind of therapy, and there can be all kinds of nucleic acid and protein tricks that you can play that are not available small molecules.
GEORGE CHURCH: But I wouldn't write out-- I wouldn't say that small molecules should be ignored, by any means. They have all kinds of advantages. I think, whatever we do, it's going to be a poly pharmaceutical, meaning multiple different pathways simultaneously. Because as some of my colleagues have pointed out, if you just get one of the pathways of aging or cancer, you might gain three years on average in the population.
GEORGE CHURCH: You really have to whack all the moles at once to really get the aging reversal that we're looking for.
ALEX PHILIPPIDIS: And, George, a couple of years startups have focused on using blockchain. There's HLTH.network, which says it's created the first global omics data sharing and analytics marketplace. Three years ago, you co-founded Nebula Genomics with the promise of offering lower cost sequencing of data that you can still store securely through blockchain. Now, earlier this year, Nebula was acquired by ProPhase Labs for almost $15 million.
ALEX PHILIPPIDIS: Why was that company sold? And what form will your involvement have going forward?
GEORGE CHURCH: Yeah. You can think of it as a merger, if you want. ProPhase gave Nebula the ability to-- an experience in direct-to-consumer. So that was what the ProPhase side of it is providing-- and larger scale, scaling up faster. The core that Nebula's providing, in addition to the first $300 genome-- Veritas had provided the first $1,000 genome in 2016.
GEORGE CHURCH: But what Nebula is providing with a variety of encryption-related tools-- the blockchain public ledger is an unalterable way tracking all the ways that the data has been shared. But the homomorphic encryption query allows you to ask questions about the data without actually ever decrypting it. So rather than sharing your genome, we're giving your genome away.
GEORGE CHURCH: You retain it. And there's very circumspect and limited kinds of queries that can be made, but nevertheless very powerful. For example, a physician could help diagnose you without ever possessing your genome. And so it's showing attention to one of the things that people list is the reason that they're not taking advantage of this incredibly cost-effective bit of what should be one of the biggest bits of preventative and personalized medicine in history.
GEORGE CHURCH: And people have various reasons. Either they haven't heard of it, or they're worried about the privacy-- worried about insurance companies in some vague sense. Or they just don't think it'll do anything, again, for a variety of reasons. I think the main problem is the 1% problem, which is the same reason that people didn't accept the surgeon general's warnings about cigarettes.
GEORGE CHURCH: And they didn't buckle up even though they had seat belts in the car, and they had a law. They still didn't buckle up. It's because they felt like, well, 99%'s pretty good lottery odds. And it's not on a public health basis. Anyway, I think we mostly got past that with-- and COVID-19, another one. 1%, I'm good with that.
GEORGE CHURCH: But you're not. You are until your loved ones start dropping off.
ALEX PHILIPPIDIS: Yeah. And looking at another startup that you co-founded, eGenesis Bio, which focuses on xenotransplantation, human compatible organs through multiplex gene editing. How did you get interested in xenotransplantation, and what's the company been doing lately?
GEORGE CHURCH: Yeah. So frankly, what happened was I had just been vaguely aware of it for years. It had been pioneers working on it for two decades before I really got involved. And what happened is we made-- or I don't say we made. Enough noise was made about CRISPR that the pioneers in xenotransplantation, who had been kind of circling around one key gene, which was alpha 1-3-galactosyltransferase, which caused a very acute reaction of animal organs-- like in hours, not in months-- just a immediate reaction.
GEORGE CHURCH: They thought, if they could edit that gene, that would be the cool thing. But then they later realized that that wasn't nearly enough. And collectively, everybody had their favorite gene. They invited us to join into the party with CRISPR. And when we counted them all up, there were over 40 genes that we had to edit, which we now have done multiple times, in multiple different strains of pigs, for various reasons-- and did a sibling company in China, in Hangzhou, called Qihan.
GEORGE CHURCH: But China had its own problems with African swine fever virus, which made it harder to do any kind of pig work. But eGenesis-- back at the ranch in Cambridge, Massachusetts, Genesis has done a really great job of producing multiplex or-- it's really a testament to how much multiplexing you can do in the germline and not mess up the organism, because there's dozens of these things that are now in, as I mentioned, pre-clinical trials in three hospitals.
GEORGE CHURCH: That's looking quite good. Hopefully, there'll be clinical trials in humans soon.
ALEX PHILIPPIDIS: And back in April, eGenesis expanded its research with Duke University to include preclinical research of gene edited kidneys implanted in NHPs, Non-Human Primates. Where does that project be-- [INTERPOSING VOICES]
GEORGE CHURCH: And also at Massachusetts General Hospital and a third hospital-- and islet cells heart. So there's quite a few. Almost everything that's currently transplanted human-to-human is probably up for grabs. I can't say too much about those studies. They're looking very promising. Once they get into the one-year range, which some of them have now, then it becomes a matter of tastes.
GEORGE CHURCH: The FDA will approve moving into human clinical trials at that year point. That's been kind of the magic cut off. But you want to make sure that it goes well. Just because you passed that point is not going to be sufficient-- but hopefully very soon.
ALEX PHILIPPIDIS: All right. More broadly, George, do you find it fairly easy to acquire seed funding when you launch a company nowadays? Or are you still having issues with some startups getting off the ground?
GEORGE CHURCH: It's definitely easier. Certainly, the last couple of years, investors have done very well, both with private and public stocks. That helps. Our reputation has gotten better and better as the years go by, which I'm grateful that that's the perception. But there still are little companies, some of my favorites, that spend more time than they should have to-- the CEO spends-- and more and more frequently, CEOs are scientists.
GEORGE CHURCH: So they're spending precious time they could be focusing on science. So it would be nice if it were even a little bit easier. We don't want to make it too easy, just like we don't want the FDA to be too easy, because there will be unfortunate things that happen if there's not some pushback. But yeah, it's better. I'll tell you the real place that the money is needed the most-- at least right now when we're doing well as an industry-- is in the period between the crazy idea and the precede launch-- crazy idea phase, where we're talking about nanopores, where you take some weird technology from neurobiology called a patch clamp, and you put it together with a DNA polymerase [INAUDIBLE]..
GEORGE CHURCH: That's too weird for words. But now it's one of the main ways of doing long-read sequencing and the only portable sequencer. So it's hard to get grant funding for that. It's hard to get philanthropy funding for it. Often, they're quite technical. Unfortunately, they don't share, with science fiction, the easy communication of sci-fi.
GEORGE CHURCH: They have all the disadvantages of sci-fi, that nobody believes them, with all the disadvantages of the highly technical science, that nobody understands them. So that's the valley of death. It's not the valley of death that most people talk about.
ALEX PHILIPPIDIS: Well, summing up, George, you've been on the faculty of Harvard Medical School for more than 30 years. You show absolutely no sign of slowing down. What are your major goals and hopes for the next 5 to 10 years?
GEORGE CHURCH: Oh, I thought you were going to ask about next 200 years-- for my personal lab, next 200 years, yeah. Yeah, I think 5, 10 years is short time with clinical trials, but it's a very long time with innovation. And a lot of these things are happening in parallel. So in the same 5 to 10-- and in fact, we've now seen a clinical trial that only took 11 months, and that's got our salivation going.
GEORGE CHURCH: But I've mentioned, at the beginning, some of the far out things that we're doing. Another one that I didn't mention is recording information in biological systems. We got a lot of attention for recording in vitro a book, my book Regenesis, in digital form and then in DNA form, made 70 billion copies of it.
GEORGE CHURCH: And that launched an industry that is now an international consortium of companies that are doing that. But I think all of that-- and this is a point that I think is an interesting feature, which is that you can write DNA increasingly easily in vivo. So there's no phosphoramidite synthesis or even new enzymatic methods that we and others are working on in vitro.
GEORGE CHURCH: It's not in vitro at all. It's in vivo. And so we've made a mouse that records about a terabyte of information in 30 nanograms of DNA, scattered through its genome, scattered through every one of its cells, as the equivalent of a black box that you have in airplanes for flight recording. But every cell has its experience with respect to developmental biology.
GEORGE CHURCH: And you could also record a growing number of physiological parameters. A group at UC Irvine took a similar-- took our method and extended it considerably to monitor hypoxia. But basically, you can have flight recorders in all your cells. And then you only have to read the ones that went wrong in some way that you can't use normal diagnosis for.
GEORGE CHURCH: So I think that's quirky. But I think that's a little more evident what the path to market might be than, say, interstellar nanogram probe.
KEVIN DAVIES: Thank you very much, George. We have to leave it there unfortunately. We would love to carry on the conversation, but we'll do this another time. Thanks so much to our special guest--
GEORGE CHURCH: Thank you.
KEVIN DAVIES: --George Church for making the time for us today and joining us on Close to the Edge.
GEORGE CHURCH: Absolutely.
ALEX PHILIPPIDIS: Thanks, George. GEN Edge is where biotech gets down to business. You can sign up for a free introductory trial at www.genengnews.com. Close to the Edge is produced by Bobby Grandone. I'm Alex Philippidis thanking you again for taking the time, and we'll see you next time on Close to the Edge. [MUSIC PLAYING]
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