hello and welcome to the genetics podcast I'm your host Patrick short my background is in population genomics and studying the genetic causes of rare disease I did my PhD at the Sanger Institute in the University of Cambridge and have been in biotech since 2018 when I started sonog genetics sonog genetics helps academic and Industry researchers to run large-scale genetic testing programs that speed up their clinical trials generate data sets for the next big breakthrough and give participants the best possible experience taking part in research each episode of the genetics podcast we bring you insights from the leading Minds in genetics and precision medicine including household names and Nobel Prize winners as well as early career scientists and biotechs working on the next big breakthrough whether you're a scientist entrepreneur executive Patient Advocate or simply someone curious about how genetics shapes our world you're in the right place thank you for listening and let's get started welcome everyone to the genetics podcast and George church thank you so much I think I could talk to you for a 100 hours and we would still have uh lots to cover um so we're going to try to do our best in 45 or 50 minutes today I was wondering you know there's tons of things people can watch Ted Talks they can read all sorts of things that you've done what are the one or two things that you're working on right now that you're really excited about that don't quite have the coverage yet or that you think could be B in the next couple of years that are important projects to you well they might might not have the coverage because they don't deserve the coverage but I'll mention them anyway um kind of pet projects that that will probably languish for years just like the like our elephant project languished for decade uh before it got money uh one of one of them is um the idea of making a a box that can turn electricity into um almost anything I teach a course called how to grow almost anything at Harvard MIT and and the idea is to make this box that that maybe sits in your kitchen and makes food initially from electricity assuming that electricity becomes abundant from a variety of sources and is more efficient in a photon if it comes from photons anyway this this box will address issues of supply chain possibility of pandemics where you really don't want to open your door uh and it and it will achieve what uh hasn't happened yet in the International Space Station nor in submarines which is full recycling anyway that's one pet thing on that one what makes full recycling so hard like why what what is the heart of the problem there well it's not part of it is people just haven't thought about uh you know electricity is being more abundant than Farmland uh and if and you can and also some of the organisms we're working on have extraordinary doubling times like 10,000 20,000 times faster than corn uh and so that means that the foot footprint can be shrunk and um anyway so uh they just you just haven't thought about electricity being in some cases an easier supply chain than other things right um less disruptable um I mean you know geothermal local solar so forth Fusion maybe and fusion yeah right um so yeah so uh the other problem is we can do full recycling for Animals just humans are a little more fastidious about you know but they they they think we think that we're not eating poop when we're eating poop all the time you know a nematode usually uh so that that kind of thing you know so so that's project number one and what's project number two uh number two is uh is biow weather maps so this is something I've working on since the turn of the Millennium and and the idea is to is to get is to enable people in participatory science where they uh um you know like weather you know where where where it actually matters to them what they what they wear out that day and things like that um but this is broaden it from weather to including all sorts of biological things Al allergens pathogens um environmental uh non-biological environmental hazards and so forth just kind of packaged together in a way that's entertaining and and useful um and that could include things like little envelopes that you have kind of ubiquitously everywhere that you know don't require Postage and you just stick whatever you want in there some you know uh some envelope you licked or you know or something that you found in your backyard and you put it in there and you don't have to give answer any questions whatsoever because where it was postmarked and the sample itself explains everything that needs to be explain then they email it back to you if you it gave your email address I guess you do have to answer that that one question so it's kind of there's a citizen science angle here right where you it you don't need you don't even necessarily need sensor arrays everywhere you could do this in some kind of if you had enough people in you know one person per neighborhood resolution you'd be you'd be fine right although sensor arrays would be part of this as well as well as things that are already going on like the CDC and Wastewater measurement I mean I my wife and I look at those almost every day for Massachusetts Co Wastewater but but it's so specific it's just Co wouldn't it be great if you just kind of like you it's like car Canary and the coal mine but Canary that can detect more than just methan yeah I I went to the Canary Islands which are off the coast of North Africa and a couple weeks ago and they the weather app actually told me that the air quality was really poor because there's basically these things called kalimas where there's a sandstorm that comes off the they're close enough to the Sahara Desert I think that they get these sandstorms but I in none of the other weather apps had it there was just one we looked at that said oh by the way the air quality is you're going to be breathing sand they have it in in towns like uh La you know right where the air quality varies but I'm all of these things are are part of weather that are usually neglected and I think it makes it much more interesting and also more more valuable uh and we finally have the cost of doing the the DNA part of this for allergens and pathogens down so low that we really could kind of um you know democratize it yeah I wanted to ask you about viruses um more generally when doing the research for this episode there was an an early timed post I think it was from December 2019 there was an article talking about you you talking about the importance of engineering viral resistance into humans and a month later we were hit with the global pandemic and obviously you've been thinking about this for for decades probably but how what's changed since then you've been doing a lot of work on this um and it's it's in the public Consciousness a lot more and than it was then but um the problem hasn't gone away right and and in many ways our eyes have been open to how bad this could be round two or round three in the the future what where's your current thinking on that well one one dramatic thing that's changed since then you're right we have been thinking about it since around 2002 as is how do you make a general solution to the problem of viruses because it takes so long to adapt to a new one I mean it took us about a year to come up with something decent for covid-19 and that's like the world record by far in terms of speediness uh and and the next one might not give us a year right um so so the thing that's happened since um that that prophecy was was that we actually we we finally got complete virus resistance for at least one organism it's it's the industrial microb equalized so it's of industrial significance but it also points to a general method we think we can do it for any plant animal or human um and and the the idea is very simple is as you change the genetic code we essentially swapped a serin and alucine in the genetic code and those are very different chemically and so when you swap swap those two EV the host is in on the game so it doesn't affect it at all but the virus is broken in every Gene in multiple places and so it can't really even evolve around it the way it would evolve around say A you know a new HIV drug uh so so that would be the the ultimate vaccine is is it protects you against all viruses even ones we've never seen before all naturally occurring viruses you can obviously engineer a virus that that would get around it but hopefully nobody would do that um so um and the challenge for human I mean we can do this for plants and animals relatively easily I mean it's it's like 10 times more work plus the you know just just in terms of number of base pairs to change but it's also uh even more work because they're a little harder to get DNA in and so forth but but anyway I mean that something we did like one little lab on a Sho string did it uh this year and published it nature should be easy to scale up but then the other hard thing is you have you only have access to the germline for you know microbes animals and plants and for humans you'd have to figure out a way to get it into a large chunk of of the cells uh now if it's if you get hematopoetic stem cells that gives you that makes you resistant to a large category of viruses um and that's relatively easy to do um and if you put it into every transplanted organ you at least make them better you know a lot a lot of transplants are initiated because of infectious disease you know hepatitis so forth um various respiratory infections um so so that would that would be the the camel's nose in the Under the Tent uh but I think with time we could figure out ways of replacing all kinds of tissues that are not common place right now if the if the need is is great enough and and possibly do it in a form that's like a vaccine um where it's not it's not a surgery it's just uh you know an injection that that where the cells find their to the right place and and replace the the organ components with with new components yeah and that that paper if people are interested is the one you're referencing is a swap genetic code prevents viral infections and Gene transfer is that right correct yeah and and what's happening there you're you're you're changing the way that the TRNA is function in some way um you're not maybe you can explain a little bit about how that works under the and I think you mentioned before that it's something you could do in in mammals as well potentially right you've done it in eoli first for for obvious reason yeah you hit you hit it nail on the head it's it's it's TRNA trickery um and I've been working on TRNA now for 51 years so uh old friend um and it it basically is there 64 triplet codons and um uh our lab pioneered changing one of those Cod codons and then Jason Chin changed that one plus two more and now we're in the process of changing seven changing meaning first you free it up so it's not it's you move it move it to a synonymous codon so you take every instance of u c uh a or G which is code sering you switch those over to the other sering the other four stearing codons and now it's quote freed up and once it's freed up then you can delete the TR for it which now makes it somewhat resistant to viruses um in fact we showed it even with the stop code on just one code on we can make them resistant to about 80% of viruses but then there's some viruses that have some tricky things like they bring in their own TRNA so the fact you got rid of the host one doesn't help and so then we we took this extra thing of swapping the serin and Lucine and and it's that's not sufficient you have to make it the TRNA that does that swap abundant enough it can't be uh thwarted by viral mechanisms like cleaving the TRNA or bringing in extra TR so we put in a viral TRNA and that was a critical component uh and expressed it at high levels anyway that that results in the host is fine virus um all viruses that we've tested and we even went beyond the lab strains we went out and got wild viruses from you know sewage and farm waste and and and found some that brought in their own t R and none of them um are detect have any detectable replication so I think we we got it and it's completely General because every every microb plant and animal has a genetic code not all of them have a virus problem but huge fraction of the ones we care about do have a virus problem yeah there's a there's an obvious direction to go with this which is around the ethics discussion but I I was thinking rather than going into the ethics for now of any individual one of these I was really interested to learn actually about some of your underlying ethical principles because I when I think about you I think about someone who pushes the boundaries both technologically and ethically and you're very famous for um you know not always having the conventional Norms that um that certainly the popular press uh have when it comes to things that we should or shouldn't do and I have the sense that there's a really core set of ethical principles that guide you for example you're vegan um I'd love to hear a little bit about the decision that there um but you're not you know you're not doing things just uh just cuz you can or because you feel like it I think there's some there's some kind of clear set of guiding North Star principles and I I wondered if you had a sense of what what those were and where they're different from what might be mainstream today but but could change in the future yeah I think again you hit the nail on the head uh uh ethics and safety are are are number one uh so ethics is safety and efficacy that's the sort of the FDA version and um and then um accessibility affordability um is not really addressed by the FDA but is is a top priority for us as well and and you're right we we we we typically do that first and it probably is easier to discuss it as a general principle than to do it one by one through each of my projects but almost every project we worked on at least from my point of view had uh some component of safety and affordability that we needed to address UPF front and so we almost always publish the ethics safety affordability stuff first and then and then reveal the you know the the potentially disruptive in a positive way uh uh technology so for example um when we brought out a method of synthesizing DNA big DNA from uh chips um that looked like it might be a 10,000 fold effect and could enable potentially making pathogens and so and so we felt so you start examining that causes you to because you're close to it I mean I don't think we're particularly more ethical but we're close to it and if we feel a responsibility we say okay what could you do about it and at the time it was kind of popular to say oh we're going to have a you know code of ethics well that doesn't do any good if somebody doesn't sign sign it or doesn't mean it when they sign it yeah and so I I thought that what we needed was surveillance and uh in particular some automated system for surveilling all synthesis and that and then that um um that was a uh resisted by the lawyers and synthesis companies because the invasion of privacy of the Pharma companies and and them being responsible for if anything goes wrong while they're not responsible if they don't look uh event those objections were overcome and now it's standard in the field uh from 2004 white paper I wrote to today it's 80 90% And it hopefully will be 100% soon Kevin esfeld and his team have produced a new set of software on top of the the old set that I think looks very promising anyway I dwell on that one as an example I could give other examples for personal genomics and for um Gan drives and Etc but uh but let's go back to the general principles uh which is to um yeah not assume that everybody is going to sign up for something uh voluntary that's the surveillance component um also uh you know think try to think out of the box is to and to listen to what listen to a broad set of voices don't don't just educate them which is sometimes consider what scientists should do is to be educ educated um and uh and you know and get that communication going the real thing is they say oh SCI should interact with the public well generally speaking the public doesn't have time uh you know they barely have interest either um even if you tell them that you know they're so used to Chicken Little saying the sky is falling that it's pretty hard to get their attention and usually when you do it's on something that isn't a problem that you know it's like I mean for example I think um germline engineering is not an urgent Public Health crisis it it's not even clear that anybody's even made a business model for it or a medical argument for it it's it's almost useless and but nevertheless a huge amount of energy is spent both in science in science ethics and in reaching the public while almost nobody is talking about the adjacent thing which is you you could use somatic cell genetics to make super solders actually more easily than you could with uh with germline uh because you don't have to wait for 20 years for them to grow up right yeah and and it's just it's just a nonissue UHC partly because there's eight billion of us that have already missed the deadline for germline you know it's like doesn't apply to us uh and so anyway um it's another example I I delved into a little bit um so so what else yeah so so listen to PE listen to the public in various ways participate in P podcasts like this one you know don't say no to journalists all you know as some kind of knee-jerk reaction they're they almost never get it wrong if you get a little bit of practice in what it is and how to talk to them um I mean I've done hundreds of interviews and essentially none of them the only ones that go only time the news gets wrong is when they don't talk to me at all right right they they take the story and they put their own twist on it yeah uh but that that's not I I I don't complain about that because you they didn't do any factchecking um I complain about the fact they didn't do fact checking but yeah on my fault but then then when the facts are wrong you're not surprised what about these area a lot of the areas that you work in that seem to be the trickiest are the ones where unknown unknowns are are kind of to the question so Gene drives and and maybe you can briefly explain what those are same with germline genetic engineering I suppose the and and the certainly with the mammoth and bringing back other extinct species the common you know the common objection is we actually don't know what could go wrong because we're tinkering with complex systems how how do you think about those cases and and how you protect against that yeah I um I mean part of it is most of these things are the the number of unknown unknown shrinks the more you think about it and talk about it and that's why it's really nice to get way out ahead of it you know like Jurassic Park started us thinking about the extinction back in 1990 and it's it's not going to be practical until 20 30 let's say 20 28 in that in that range and even then yeah so so it gave us plenty of time to think about it think of All Things That Go wrong there still will be things we miss just like we you know we missed Vio for example and HRT uh in the pharmaceutical World um but what you do is you try your best um you may be over prepare um it's better to have you know uh you know too much protection that's what I was saying earlier about Supply chains and you know if we have a little box in everybody's house already for just for general principles then we're much more prepared for other things that that could be rare and I love thinking about things that could be rare you know these Corner cases they provide us with um we don't want false reassurance what we want to do is uh over prepare anyway um so you listed um you know for germline again I think it's surveillance uh that was missing from the discussion because we now have already had one breach uh where someone spent three years in jail but he's back out and doing similar stuff uh the the breach the problem was there wasn't PE many people knew about it in advance before JK H did it uh and I I think they should have reported it right you know it it reporting it isn't synonymous with sending him to jail fact could have they might have saved him from jail since they knew about it before he did it um so uh and so they say well we didn't know who to go to that's that's lame you go to some random person and and they'll tell you some other random person and you just keep going to random people till you get the right Fe I would have started with the FBI frankly even though they don't have international they find the right person wouldn't they pretty quickly I mean I know a bunch of people in the FBI and that's who I would go to or you could go to the head of the FDA or head of NIH or and and it probably the answer the answer will come from from one of their subordinates but still you you tried you got it on record that you yeah that you rang the bell so that was that was what was wrong there and and there should be in many cases there should be a kind of a whistleblower Credo that that says that protect that that encourages The Whistleblower in some way or another but doesn't encourage false whistleblowing right so you need that you need that balance and the encouragement has to go beyond protecting The Whistleblower because that's not really encouragement it's like it's like okay we're going to put you in the witness protection program for life you know yeah great you know hence you're going to be a billionaire no you're actually gonna be much worse off um so um what was the other example you gave an addition of germine Gene drives genan drives so so there the the concern is the concern was with GMOs and General is that they'll spread uh now in practice they haven't really spread in fact it's hard to make an organism that will survive in the wild that you know that's at all different from what you took from the wild so now the Exceptions there are two that I know of and I've worked on both of them one of them is the virus resistant eoli that we we talked about earlier and the other one is Gene drives because virus resistance equoli has a selective Advantage um and that it's resistance all viruses and all of its buddies are sensitive uh genan Drive have a different ADV not really classical selection where you're selecting on the phenotype it's it's a genetic mechanism that causes 100% of The Offspring to inherit uh the drive uh the gene Drive Al um rather than the normal 50% and 100% spreads very quickly it requires sexual reproduction and a rapid generation time which people don't always appreciate when they hear about the so that means it's limited things like mosquitoes and and rodents and uh you know things things like that um if you put the wrong so so that's why the first three papers that Kevin eseld and I wrote were all about how to reverse it and contain it right um uh kind of culminating the daisy uh chain Gene drives which um where if you started on an Island um where you have the right amount of of of three different Gene drives you can keep it from going to the mainland um because on the mainland will get swamped out by the wild time um that that addresses a broad set of unknown unknowns and that it gives you the control over reversing and and containing even if you don't know what it is you're reverse what it is that the problem that you're dealing with so so that's one way of dealing with the unknown unknowns just having a general and in fact almost any technology you should have you should give some thought how you reverse it um for example you know cell phones I don't think we have a clue as to how we would reverse uh people's addiction to cell phones or addiction to oxycotton or a whole bunch of other things clearly the War on Drugs is not the reversal process that we should have thought about in advance so so that that would be one of you know you're asking some of my general strategies yes um that would good way to think about it yeah so I I suppose the Willie Mammoth will have some kind of off switch if it if it completely if it looks like it's wreck the ecosystem that we are prepared for in the sense that uh goats were introduced into uh Ecuadorian Galapagos Islands long ago uh and they've become quite a pest considering that one of the major source of income in the in Ecuador is tourism right and uh these things are tromping all over the the eggs that that the reptiles believe on the on you know on the ground um and and rats are a similar thing in many many islands not just the galpagos they they eat the bird eggs and the bird young uh for rare exotic beautiful birds and song birds so uh but they got rid of the goats uh Ecuador showed that you can get rid of how do they do it anything you can see uh you can get rid of they just give people let them hunt or what do they do no they had to go beyond that you know some sometimes governments will take the easy way out which is they just say it's open season on snakes or something uh but it usually ends up people killing the wrong thing and right and not killing the thing they should be and not getting enough of them um but no they they they put uh trained marksmen in helicopters and just right and goats really can't hide from helicopters and for rats they tend to put rat poison down in little packages on the island however that that's worked on I think A Hundred Islands but they're about 600 more Islands to go and those have problems with um you know farm animals and humans being on the island um kids and things that don't know not to eat the rat poison so so that that's where genan drives might come in eliminating the rodent populations so were invasive species yeah it sounds like could be a more humane way to do it as well you you the idea would be you introduce a rodent population with the gene drive and then after a couple Generations it it minimizes right yeah yeah and so so no you know as as they say in the movies no animals were hurt in the in the filming of this movie right just reproducing that's all they had yeah and I think dying of warrin uh which is a you know reduces your clotting ability is not a pleasant way to go but no you just having um the rat equivalent of birth control is not so bad yes I I want to ask another more general question which was about your creative process you are you're a prolific inventor you set the record uh may let me know if it's not still the record but I think in 2018 you spun off 16 biotech companies in a single year uh you have hundreds of patents hundreds of companies I I'm interested in what you do do do things just come to your mind and it's and there is no process or do you have uh do you read widely I've just really curious to learn about what you do to generate so many interesting ideas well that's a good question and probably the short answer is I don't know but uh nevertheless since the question is is asked uh uh you know I think uh uh a16z and Dre and horoz wrote wrote a a thing on what's what's in the water in the jur lab yeah and so so I reflect on it so the one thing is I think that people that are that grow up different in any way doesn't you it doesn't have to be some specific kind of autism it's in any way you know if you're a little bit chubby or if you're too thin or you know you know get good grades or bad grades or you know whatever it is it makes you feel different and then you start thinking different so that's one thing uh and I was I was different on a number of different axes that we don't need don't need to go into um but um so it doesn't have to be some mental gift uh it's just just being slightly ostracized um and it's not even that it's not even not even not always that painful uh so a second thing is listening so just like the ethics conversation we had it's important for Innovation which is you listen to people and don't discount what they say now very often they don't the people that mention something to you all they're doing is they're like jogging your you know your creative juices they don't they they neither have the idea nor the wherewithal to do it but it's good to give them credit if you can anyway and an example of that um just to be concrete um I was interviewed I think in 2008 by Nicholas Wade and so I give him credit for this uh you know he was he was doing a story on like a tiny bit of the mammoth genome that had been done uh by the Penn State University team and um and he was trying to figure out is there if there was more to the story than just some pathetic amount of DNA being sequenced uh and he knew that that my lab had developed some of the tools that was being used for reading D ancient DNA and we also developed tools for writing DNA but not ancient DNA so he put the two together which I think is his uh maybe he was influenced in term by by Jurassic Park yes um because this is this is 2008 he had 18 years to think about it uh and uh and so he asked that and and instead of me saying look you know that's not my department you know that's going to look that's going to look silly if I answer that question every my colleagues will ridicule me I just said look a legitimate New York Times journalist has to ask the question I should try to answer it even if it's not my field in a way it was my field because it brought together two of my things which were reading and writing DNA and so I estimated you know how much it might cost and I was as usual I was underestimating the problem uh but uh and then I went off and thought about it and said M we could do this really could do this and we I should think of what's the right species you know it isn't necessarily the first one that was suggested um yeah by Nicholas uh and then I started digging around and found Sergey zov's work on uh the impact of removing large herbivores from the Arctic how the negative impact on the diversity of the ecosystem and in particular the the protection of the permafrost keeping it Perma and frosty uh and I I was very influenced by that and I met him shortly thereafter he and his son came and visited uh and then I reciprocated by going to Siberia um I think they got the what was that like was it was that have you been back Siberia it was it was amazing the timing was amazing it was uh the first year in history we didn't know this when we went it was first year in history that um the summer melt didn't fully refreeze we saw the consequent we would go into these deep underground caves that apparently everybody in Siberia builds for storing their their summer fish uh for the you know all the way through so they don't need a freezer they just stored underground but anyway there was evidence of melt uh there and so forth um it was also amazing because we we had three film Crews mainly because it was one was on Stuart brand who was a Pioneer in a number of different fields and and and he and I were essentially doing this together um and and uh and then the whole business about the permafrost melting and so forth there uh it's releasing it in the for a lot of it in the form of methane and so you get this dramatic uh image of going out poking a little hole through one of the The Ice in the lakes and holding a match and it's just you get this flame coming up out of the out of the ice and it's just it's just Unforgettable you can't can't see that and it's not just the Lakes it's it's the the around adjacent to the Lakes all the way out into the Arctic Ocean there's all these methane clathrates at the bottom of the ocean so it's it's about uh 100 200 times more of that at risk than than the carbon that we're worrying about that comes out of our so-called polluters uh in in the human race so anyway it's a big deal um have you um we mentioned Jurassic Park a couple times have you ever met Michael kryon or Stephen spieler what do they what do they think about your Mammoth work if they had a chance Michael unfortunately has passed but he was a a student medical student at Harvard Medical School and and I have to say you know I've admired I've read most of his books uh and admire the way he thinks about things um but I think he didn't he should have finished medical school at least finished the the course on biochemistry because one of the things that he put in the book that the the first book uh uh thoracic part was uh the lysing contingency it's called and uh and the idea is that make all the dinosaurs addicted to lysine as a in their diet and then if they escape then they don't have any lysine the problem with that is that all microbes plants and animals have lysine in them in abundance it's an essential amino acid and and no matter what food they eat scab line so it was a kind of a I I don't think he did it tongue and cheek I I don't know what well yeah did it but he's in Good Company because the NIH did a very similar thing their guidelines for biocontainment were based on diaminopimelic acid which is also present all over the place in particular present wherever eoli grows because eoli has diamino pic acid so there's two examples of how not to do biocontainment we published an example in 2015 about how to do it where you use a chemical that is only producible by organic complicated organic chemistry and doesn't occur in the wild and that chemical was B A but there could have been any of a variety of organic chemistry produced amino acids uh for example but anyway uh the other interesting connection with Jurassic Park that I have is uh when it first came out I I saw that a couple of the pages were covered with DNA I say that's pretty rare to have actual DNA sequence filling a page uh so I said I wonder what that is they called it dinosaur DNA but I I knew back in 1990 there's no way that have it and uh s i I wrote a program to figure out what it was back then we didn't have blast and other great uh tools and uh and it turned out it was uh something I had done as a first year graduate student uh together with Greg sutliffe which was the the plaz PBR 322 and he had stuffed in kind of random sequences here and there but was 90% it was from the eoli plasma I thought that was kind of funny too interesting dinosaur DNA as okay is there is any dinosaur DNA well preserved enough I know in the story it was in Amber or something but it's it's way further back than all the ancient we're used to working with is it even is it even possible what you think I I I have a a principle of of avoiding the word impossible my my life and my work in my lab um you know it's too easy to dismiss things and that's another thing getting back to your question of how to invent new things is just just just instead of putting it in the trash can putting it up on the wall where you can say hey that's a challenge rather than a piece of garbage almost everything that I've done has been uh dismissed by a large number of people as either impossible or useless or but typically both uh uh that's when you know it's a good idea right they tell you it's imposs that's what I double down the definition of fanatic is somebody who wants they anyway so your question was yeah I was uh I guess what would the conditions need to be for preserved if you wanted to do the the dino version of the mammoth so there there's two answers I mean one one is the age keeps slipping going further and further back uh um and and each time they say well this is it this is as far back as you can go because we can do these mathematical calculations of Decay rate and blah blah blah so at one point I think it was like 100 100,000 years was considered some gigantic record maybe it was 10,000 before that and then 200,000 now I think it's 2 million um which is getting into the range um the but but then the other answer is you don't necessarily have to get the DNA to get the answer so for example you don't have to get the ancient DNA so so for example you take modern DNA and reconstruct philogenetic trees you can reconstruct the ancestral DNA and this has been done in a number of groups where they've reconstructed uh either the common ancestor of ruminant mammals or the common ancestor of all life and you know and they think that those proteins are probably adapted for 65 degrees so you can you can actually get information about what life was back that then now it's hard to get the cyst regulatory DNA and RNA is probably going to be a little hard reconstruct from that method but but again never say never you know uh also in the Third Way is just by studying modern organisms and studying the bones or whatever you have from the ancient times and figure what modern mechanisms would it take to make those bones so again yes we don't know how far that method can go so you could basically three methods which are uncertain in a very promising way yeah fascinating I am I was curious I had a a couple more before we run out of time here I was curious about um the your decision long ago to become I think the first person to basically open source your medical record you're the fifth person ever genome sequenced um you know people know that how involved you were I was wondering whether your how your position has changed on open sourcing one's medical information through everything you've learned through pgp everything everything yourself you've been proven right in a lot of ways that uh you stood the test of time nobody has designed virus to go after you yet or done anything crazy with your data but I'm I'm wondering what you've learned because it's been a it's been a couple decades right since you started this well this was an interesting exercise and thinking out of the box too not not only thinking out of the box of how um medical consenting was done but also what could go wrong uh so what what is going wrong already and what's could go wrong so so what was going wrong at the time I proposed the personal Genome Project was that people were being consented with the false promise of anonymity other words they said there's no way that anybody can identify and they later partly thanks to my uh U Consciousness raising they watered it down to well there are ways we think they're unlikely um but they were actually quite likely when I raised the the alarm uh because at the time you know things like millions of Veterans Administration and hospital records were getting hacked or or lost in the subway and right and so forth so um and in fact the the the value of medical records was was estimated to be 30 times the value of your credit card theft um because credit card you cancel immediately while all the medical records you can't cancel you know like your mother's make name and your social security number and stuck yeah anyway um so that was that was the out of the box on what was wrong oh the other thing was wrong in advance was uh that if you found out something about the patient you couldn't tell them so if you found out that all they had to do was take drug X and they'd probably be fine and they could do that in cons in consultation with their physician you can't tell them that you couldn't tell them that back then and so I felt that that if you got the data from them you you could give it back them as long as they've been proven that they are capable of handling that information so so that's why we put in requirement to get 100% on an entrance exam and it wasn't everybody everybody I I think could pass it uh um that W that was uh and so that so then um so on the side of what could go wrong if we neutralize those two problems um uh we would we put that in the consent all things we could think of and and one of them was like you said a pathogen that got your name on it another one was um that people could take your DNA and plant it at a crime scene um and we tried to make scenarios that were more risky and maybe even more unlikely uh but to figuring that if they were okay with those scenarios they would also be okay with the unknown unknowns that we couldn't we couldn't list so the idea was just kind of go overprepared um and then we could handle the unknown unknowns which you know again it was a question you asked earlier that was quite appropriate here too and so fast forward to today he asked what lessons were learned well the pgp I think has turned out to be a a pretty big success is we didn't set out to um to be the dominant sequencing group I mean you know I I you know anytime I want something done in an industrial scale I launch a company I don't try to do it academically now there are some academic Labs that have tried to compete with industry but you know for either genome sequencing or gene therapy I just more more power but but so I I hope we will sequence uh all 8 billion people or or the subset that are willing to get to get educated and and sequenced um soon BEC because of the commercial uh components um because you know there's trillions of dollars that could be saved if everybody got sequenced and that's a separate conversation for why I think that's true um so for the personal Geno project was not successful in being dominating the sequencing field it was successful in showing that you that you could test out a bunch of we tested out almost every technology for all multiomic things that are very standard now which were exceptionally did bomic microbiomics immunomics uh proteins uh um Medical Imaging and and and we didn't make them available for every person but whatever we got available we would make it available to the public yeah and so it gave the public an idea of you know how you would integrate these things so forth also we became because we were the one of the only ones that had a consent that that consented you for reidentification and for commercial use those were showstoppers for a lot of projects and and Commercial use in particular um but we consented them for that and that turned out to be a good thing so for example the nist National Institute standard technology used our samples in preference over every other sample in the world because of those two Clauses um and they're continuing to they're they're they're uh increasing that not just for providing DNA standards worldwide they made tens of thousands of ampules of of uh from Trio trios mother father um Offspring um but but they're expanding it to to cell line so forth and the cells in the personal Genome Project have been used for a variety of projects because even though you might be able to encrypt the DNA information it's hard to encrypt the DNA in the cell that you're Distributing to all these lamps so again important to to make sure they're okay with it in advance rather than you know coercing them after it's too late as was done with Henry Henry LAX the hila cell line they sort of after the fact they're getting ready to publish it both in Europe and America and they they said to the family here sign on this thing you know we've already we've already avoided your your privacy we just want you to be okay with it and they actually weren't okay with it is my understanding they signed anyway a last question I wanted to leave us with here was your prediction on societal views on genome editing and embryos is something we touched on a little bit today um and I have there's an interesting real world example that uh episode 59 of our podcast I had the pleasure of interviewing guy named Daniel barvin who uh lost his father to ALS found out that he had the C9 ORF 72 expansion and then made the decision to undergo IVF and and pgd to try to ensure that he didn't pass the the gene the expansion onto his child and I think this is an example that probably a lot of people look at it and say this is um this feels this feels okay ethically and and I understand here and I think you've made the point for a long time that we do a lot we make a lot of decisions on behalf of our children and and um genome editing is in what ways is it different in what ways is it not I'm wondering if you could speculate a little bit on how societal views may change over the next decade or two on this um as the technology becomes more available as well well this actually integrates a number of topics we've touch touched on um uh I think so editing is often used as the bud buzzword for gene therapy more generally and cell therapy is kind of I think of his gene therapy done xvivo and then reintroduced in cellular form um all of these are I cluster together um but if you but then there's a a version of that where it's done in the germ line and I think that ALS you people will come up with with Arguments for germine but usually there's a much better alternative uh and and first I'll talk about the alternative to to gene therapy uh so I'm heavily involved in advancing gene therapy but I think a fundamental thing I thought was wrong with the field when I entered it uh and have been working ever since just like I helped lower the cost of reading and writing DNA by 20 million fold we needed a similar thing for gene therapy because it was the most expensive drug category in history um up to $ three A5 millionar per dose um and and I think that the misunderstanding or the willful uh misrepresentation is that there is an alternative to to the $3 million a dose which is genetic counseling which is somewhere around $300 for a lifetime Gene counseling and it's dropping in price we're figuring out how to we the automate a lot of the counseling parts and and the price of the genome itself has dropped to 250 it keeps dropping so that that needs to be seriously considered and we need to think more it's it's been a solv problem since the mid 80s when Doria sharim uh uh showed that you could apply this to at least one Community that's willing to adopt it and eliminate or Reduce by tenfold um you know nine different genetic diseases like like T saxs which is devastating you know killing kids at four years old it's devastating for the whole family so so there is that that alternative to to to gene therapy in general and I think uh in the form of invitro fertilization um I mean you can go much earlier and you you can avoid all the ethical issues of terminate uh pregnancy termination and IVF um but uh IVF is almost the ideal way of dealing with um dominant diseases um and which you can't really do preconception um and uh so so one of my companies Orchid Health has a system by which they sequence every single IVF embryo to find the ones that that uh since we're only allowed to implant one embryo at a time now to avoid octom moms uh we uh uh a lot of them don't take you know they they and that's um kind of gut wrenching experience maybe even more so than a than a miscarriage in a normal pregnancy um partly because of the cost and the hormone injections it's just just much more painful process than than a typical pregnancy so um so with orc at Health you can identify the ones that are more likely to succeed in the implantation and and uh developmental process um I think that would that would solve ALS and and almost all both recessive and dominant diseases unless you have a vast number of different genetic problem polyenic and it's well polyenic uh it it could be that if you fix one of the polygenic it becomes a little less polyenic put something protective in there and clear it out a lot of polygenics we live with I mean you know a lot of essentially all of us have some polygenic disease um fact all of us do have the polygenic disease of of dying before we're 120 years old um but we we consider it normal that's actually a topic that um we could probably spend a whole hour on but maybe we'll I'll I'll follow up in three or six months and see if you want to talk we have a strong program in in aging reversal but uh back to the The Germ line I think that that can be avoided by genetic counseling in particular I IVF if you have a dominant Al um but uh the the other the other thing about it is it really other than that there's in including that there's really no argument for it is is that there's uh you know like I said eight 8 million of us are are past the point where it would be a benefit to us it might be a benefit to the small number of babies that are born each year but there's Alternatives that are much more cost- effective yeah amazing well thank you This was um I I'm amazed at actually how much Gr we managed to cover and it's a testament to how uh how much you've thought about all these areas so thank you so much for the time and for sharing this with us yeah well thank you it was a very um enjoyable uh interview and uh you you hit on some angles I think or they pleas articulated the way you did so good that was my hope I um I've been I've been hoping to interview you for a long time you obviously have uh had a prolific career so uh thanks again yeah thank you that wraps up this week's episode of the genetics podcast I'd like to give a huge thank you to our guests for sharing their valuable insights and experience and thank you as well to our listeners as always for tuning in if you enjoyed today's talk the number one thing I would really appreciate from you is if you could share it with a friend or colleague who you think would enjoy it as well we would also really appreciate if you could subscribe to our show and give us a quick rate and review on Apple podcast spotifi or your favorite podcast platform both of these things help us become more visible when people search for genetic and precision medicine podcasts and we're always eager to hear from you please reach out to us with any questions or feedback on social media you can find sonog genetics on Twitter LinkedIn or visit sonog genetics.com finally a big thank you to the team behind the scenes who make all this possible in particular Amy cousins and Sonia sha who produced the show and James Pierce from selected frequencies who handles the audio engineering I'm Patrick short your host and it's been a pleasure thank you and we'll see you next time on the genetics podcast
