Scientist Stories: Greg Verdine, The Future of Human Biology

Good morning, everybody. Thanks for being here. My name is Megan Field King, and I'm a reporter at STAT. Just got introductions to everybody, but I'm going to start off by giving these three folks a few minutes each to talk a little bit about their sort of big picture highlights. Level thoughts on today's topic, and then we're going to move into some questions for me, and we're going to leave lots of time for questions from the audience. So be thinking of what you might want to ask. So with that, we'll start with you, Greg, since you're closest to me, to get started.

Yeah, what I, what I took as the theme of this session is really the broader question, not, not just of the impact of genome editing, which is worthy of discussion, but just thinking more broadly about the impact of genomic technologies and related things on the future of human health and welfare. I come to that, having been to that question, having been a professor at Harvard for a little bit over 30 years and having been a venture partner in several venture funds that have been involved in developing therapeutics, Third Rock, TPG, Wuxi Healthcare Ventures. And then in the last several years, I've gotten involved in actually running companies. Initially, while I was professor at Harvard, I founded Wave Life Sciences, a genomic medicine company, and then Fogg Pharma and LifeMind. So all focused around this idea of creating actionability for the genomic information that we're getting from sequencing human beings.

Okay. So, you know, when you're inside, you don't understand how important what's happening is. And all of you are creating something that's really strange, which is a parallel evolutionary So for 4 billion years, basically all life on Earth depended on two actions, right? Natural selection, random mutation. And when you go and you say, "I'm not gonna let this forest be. I'm going to tear down this forest and put a cornfield here," or, "I'm gonna put a soybean field here," or, "I'm gonna put a suburb here," or, "I'm gonna put a garden right here," you're practicing natural selection. Except it's unnatural selection because it's not what nature would do if it was left alone. It's what you're choosing to do. I'd like to have some little flowers over here, and I'd like to have some cows over here, and I'd like to have some cats over here, and I don't like bears, and I'm gonna get rid of the wolves. And what that's doing is it's taking a natural system and it's creating a parallel branch of evolution, which is a human-directed branch of evolution. And that's unnatural selection. And that's about half the surface of Earth today. So that's a big bloody deal, right? Because it's all of us choosing what's going to live and die, not what nature's choosing to live and die. And that's a superpower. Because that's not like leaping tall buildings in single bounds. You can do that with a helicopter. But deciding at least half of what lives and dies on Earth is a big bloody responsibility. Then the second part of this thing is you've had random mutation. So, you know, this thing kind of randomly goes along and grows an eye and has 2 or 3 cells and has 5 cells and has 10 cells and evolves into things. And 99.9% of that stuff has gone extinct. All right, so you have these waves of natural selection over random mutation. What all of you do is to flip that system on its head. Because what all of you do is you practice to pick a random two words, intelligent design. You're basically saying, I want this gene here to make this. And that is the opposite of random, right? That is directed evolution. And when you're practicing these things, what you're doing is you're creating a a completely parallel evolutionary branch that allows you to create things like new life forms. And again, that becomes an awesome responsibility. It gives you extraordinary abilities, gives you abilities that no other species, no other human has ever had before. And ground zero for that is right here. And so what's fascinating about this place and a couple of other spots, right? I mean, there's some in San Diego, there's some in San Francisco. There's a couple of other spots, but it's very few spots in the world that are guiding the future of life and the evolution of life on this planet. And it's getting really interesting because you're beginning to get these experiments where, for the first time that we ever know of, you have life forms that are not based on the 4 base pairs of DNA. So all of a sudden you get ATXY instead of ATCG. And then you get ATCGXY plus 2 more. What that does is it takes your dozens of amino acids you can play with and puts into the hundreds of amino acids you can play with and the thousands of amino acids you can play with. And it begins to show that we are not a unique solution. It begins to show you that you can create heredity based on different chemistries under different circumstances And you can begin to think of life forms that could live, say, in the liquid methane seas of one of Neptune's moons. So your palette is just growing an extraordinary degree. And, you know, the two folks who are sitting on either side of me are two of the high priests of this stuff, because if there's anybody leading this stuff in the world, it's these two. And what they're doing I think is crazy underestimated. I think when you think about what was important 2,000 years ago that the Romans did, well, who was the richest person then? That's not the measure. It's who was the greatest artist, who was the greatest writer, who was the greatest philosopher, and who were the greatest inventors? And what I think we fail to recognize often is just how important what's going on here is. And who's walking into this room and what the consequences of what all of you are doing are. And we have to think about those consequences because our responsibility is to invent it, but it's also to guide it and to talk about it and to talk about possible futures. So I'll stop there.

Yeah, so just, I'm a I'm basically a lab rat. I both do experiments and I am an experimental subject. And what I think the thing that makes this all possible, what Lon and Greg are talking about, is an exponential curve that is actually accelerating. And that— and we're harnessing it. So we've brought down the cost of sequencing and synthesis about 10 million-fold, and nevertheless people can make a profit even though, you know, if you brought down the cost of just about anything else 10 million-fold, that would not be good for the industry. So that, for better or for worse, that encourages me to keep bringing prices down, both for equitable distribution of wealth but also for wealth creation. Editing has not been 10 million-fold. It's a little hard to measure, but We just had a— just published a preprint where we improved editing for one of my obsessions, which is multiplexing, from our previous record of 62 edits in a pig cell to now 26,000 edits in human cells. You may not feel that you need 26,000 edits right at the moment, moment, but there was a time where we didn't feel that we needed to sequence more than a piece of a gene at a time, that anything else was ridiculous. Now we're in an era where we— if we want to check a base pair that we just changed, we sequence the whole genome just to make sure that we didn't change something else. So you get used to these things quite rapidly. You might say, oh, that's very great, you can bring down the cost of sequencing and synthesis and editing, but it's not going to affect pharma. You know, that's going up. We all know that. And maybe that's a good thing. Especially as we get to precision medicine, it's going to be incredibly expensive per drug. In fact, I'm embarrassed to say that I'm part of the revolution that created the most expensive expensive drugs in history, which is gene therapy and gene editing. But I think it— we can, if we wish, accept the fixed costs of doing large clinical trials and maybe even the fixed failure rate of, you know, 4 to 20% success. But nevertheless, if you have a drug that everybody uses, then you then you have a big denominator and it can be quite affordable. And the one sort of class of drugs that probably everybody might benefit from is something that reduces decline, reverses aging, extends life in a way that we're healthy for longer. That would at least buy us some time to get the rest of our act together. So, maybe more about that later.

So in the vein of getting our act together, I mean, there's obviously been a lot of conversation in the last few months about the ethics of germline editing in humans. But I'm curious what sort of conversations you think we need to be having both about that but about other technologies that are emerging that we need to be talking about right now. And whether you think we're having those conversations. That question's for everybody.

Everybody is looking at me. So, yeah, so I was somewhat involved in this. I'm one of the few people who've seen the primary data, the two articles that J.K. Huh produced for the he was outed by Antonio Regalado in November. I just, first I want to say that I think that we're maybe slightly overdoing this in the sense that it would be like having moratorium on something we already have laws on. A moratorium is not nearly as impressive as a law is with enforcement where you're not supposed to dispense drugs drugs without approval, for example. And also I think that it is possible that this will— I'm not making a bold prediction here, but it's possible that this will pale in significance to somatic therapies in general, not just gene therapies or not just editing, partly because there are only 100 million people born every year, but there are 7.5 billion of us. Who can constitute a bigger market. So that's one thing, bigger market. Second of all is the feedback loop for germline is, you know, if you're talking about, say, cognitive enhancement, it's 20 years. If you're talking about aging, it's 60 years. It's a long feedback loop, which is generally discouraged in clinical trials and investment. While if you did the same sort of things on an adult, you'd have faster feedback, bigger mark, and so forth. So I think it's kind of like this idea of banning something that's already banned, or banning something that's actually kind of not that useful. It would be like banning jetpacks or something. It's like, yeah, okay, you don't need to because nobody's really selling jetpacks. Anyway, that's mine. I could go on, but maybe specific questions.

I think the conversation really in all these things is not about whether changing a genome is intrinsically good or bad. It's about the risk-benefit and subjecting recklessly, you know, children to risk. So I think technology is going to provide all kinds of avenues that allow one to manage risk while altering genomes in an increasingly precise way. So I think there's no question we're headed for this in the future, and it's a question of how it gets implemented. One thing to bear in mind is that if you take a blastocyst that's at the 200-cell stage or so, you can take a cell out from that early embryo and fully sequence it and even put a cell into an embryo that's been fully sequenced. And so that kind of technology creates the opportunity to know exactly what one is doing when one is altering a genome. In fact, you know, I was going to make the point here today that we're probably headed for a future in in which sex is just for fun and it's no longer for procreation, that the technology to analyze the genetic status of embryos is going to become increasingly important. And it's already being implemented in certain areas of genetically bottlenecked populations. In order to, for example, to do in vitro fertilization, remove a cell from the embryo, fully sequence that embryo, and decide on that basis what should be implanted. So I think that to me the bottom line is the conversation needs to be about risk-benefit and not the intrinsic value of any of these technologies. They're clearly in our future.

So I'm going to riff a little bit on what you were talking about, especially because you went down the sex path. It's always good to—

I always go that way, Juan.

—continue those conversations.

That's my go-to thing.

You know, it wakes rooms up. So, look, I mean, it's fascinating to think what happens if you had access to a time machine. And so you bring back your your dear old grandparents, they're sitting in front of you, they're 21 years old because it's a time machine, and you're going to talk to them about sex. And just think about what he said. "Dear Grandpa, Grandma, let me tell you about the birds and the bees. Do you know you can now have sex and not have a child?" And their eyes would get really wide, right? Because for most of human history, sex had a consequence. And we have completely decoupled sex from the consequence on a pretty consistent basis. Then the second thing he said, "Oh, by the way, you know, in vitro fertilization today," and, you know, grandpa and grandma's eyes would get really large because they'd say, "In vitro what? So you're gonna take an egg and a sperm and you're gonna mix them in a little plastic or glass dish and two bodies are never gonna come together? Well, you know what, we used to call that the Immaculate Conception. We thought it was a miracle, and you're now telling me you're performing 5 million miracles a year." And then this stuff about you freezing this stuff and having a surrogate mother, so you can have identical twins born 20 years apart. So you've now decoupled sex from consequence, sex from contact, and sex from time. Okay? And to them, 2 generations ago, this would be like really strange birds and bees. Now, fast forward this. The stuff that's going on in labs like yours is stuff which will lead to the same kind of conversation in 2 generations. So now your 70-year-old grandkids bring you back and they talk about the birds and the bees. Do you think sex is going to look anything near what it looks like today, right? When you can transplant uterus, when you can begin to have calves that are being conceived and grown in the equivalent of Ziploc bags outside a calf's body. Now, as you push that forward, it means that males are gonna be able to have kids. It means that kids may not be carried inside the body. It means that it might be much more accessible and easy to change things if the fetus is external. It means that your grandkids, if you don't apply this technology, they're gonna say, so I had a P53 or a BRCA and you didn't edit it out? What the hell were you thinking? Right? And, you know, stuff we take for granted two generations ago would have seemed utterly weird. And you can't be a futurist, but what you can do is you can take the current trends of stuff that's going on in George is just sitting there tinkering in an innocent lab. No, pay attention to what George and Greg are doing, right? And then figure out if-then. And that makes for much more accurate predictions. Don't invent stuff out of whole cloth. Look at what all of you are doing and then think it through for 5 years or think it through for 10 years or think it through for 20 years and look at what already happened. And then put it on an exponential curve. And then think about the ethics. But the ethics is really complicated, right? Because before all these procedures, had the majority been asked, the majority would have said, hell no. But once baby Louise Brown is born, within 2 days of that photograph coming out, you go from majority no to majority yes. So it's really complicated debates, right? In a polarized time where you're on this side or you're on this side, nuance and humility is something that's missing. And nuance and humility is really important in the stuff we do.

And sort of jumping onto the issue of ethics, which is just obviously such a big one in this area, I'm wondering, A, how you think the public A, if the public should get involved or be involved in this conversation, and B, if you all could expand a little bit more on the ethical issues that are surrounding the technologies that we're talking about, in particular— and I know someone had touched on this briefly— but when it comes to making sure that new biomedical advances are equitably distributed.

Anyone can start. Yeah. Well, I brought up the distribution problem. There are very few technologies that actually are. You know, we're certainly making progress on everybody getting clean water and access to electronics, but it's still quite far away. You know, maybe there are 6 billion cell phones, but they're not equally distributed. One thing that is equally distributed is a biotechnology, which is smallpox. We are now at the point where you You no longer even have to have a few pennies for smallpox vaccine because it's extinct. So that's an example of something we can do. I think that gene therapy could be made something that you could take orally and it could, you know, you could make it very high efficiency and safety. But right now it is the most expensive means in addition to IVF, which is quite a bit more inexpensive, as Greg pointed out. There's something even less expensive, which is matchmaking, which has almost eliminated 9 genetic diseases in the Ashkenazi community. And why we haven't scaled that up to the entire world is an interesting question, because that could be nearly free now that the cost of sequencing is nearly free, and that many of— much of what you want to do in terms of matchmaking is essentially as easy to computerize as anything else we've done already. So I think that's one way of making it equitably distributed. It's, you know, the first step is to not say that it's impossible. If you start saying that it's impossible, then it greatly changes your attitude towards— and it's not even necessarily that far away. Some of these things, you know, we predicted that it would be 6 decades to get an affordable genome, and it was about 6 to 10 years. So don't assume that it's that far away.

I think for most of these technologies, they are fundamentally democratizable. You could have a high school student do genome editing in a human cell without any trouble whatsoever, whether they would do it at the highest state of the art. And I've been reading this book. Book by Yuval Noah Harari, his 21 Lessons for the 21st Century, and he, I think, makes a compelling argument that what we really have to be worried about democratization of artificial intelligence, that that's much harder to democratize than most of what we're talking about here, and it's really a question of time displacement, whether it happens now or it happens 20 years from now, even patented Medicines will go off patent in a blink of the eye in terms of human history. So I think to the extent it's where educators can have, I think, a significant role. And we have to do, I think, a much better job. I think this also extends to the FDA, that I'd like to see the FDA embrace a broader role in education and really allowing people to make an informed decision. And I think that we as scientists need to work harder to help to educate the public. I think George has been very, very good at that. We all have to— Eric Lander has been particularly good at that. I think it's a responsibility that is probably going to come from people who spend their time time teaching undergraduates at places like Harvard and Princeton, Berkeley, Caltech, UMass, whatever. So I think we have to focus our attention on it.

So I'm going to take a very narrow slice on ethics, which may be relevant to some in this room. So years ago, when the Beltway used to move in DC, every morning at a certain time there was a backup. And it drove the traffic authorities nuts because they had this brand new beltway, it moved except in this one spot. And so they tested this and they tested that and, you know, finally there's a newspaper story, they can't figure out what's going on. In comes a letter to the newspaper, Washington Post, says, "My name is John Nestor and I get on every morning and I go to the far left-hand lane and I set my cruise control at 49 miles an hour." The speed limit is 50, and for some reason people honk at me and want me to get out of the way, but I'm following the letter of the law. And I can't tell you the response to that. I mean, people were just furious that this guy would do that. Well, absolutely hysterical, except guess where this guy worked? He worked at the FDA. And he never approved a drug because the letter of the law says The drug has to be safe. And no drug can be safe. There's always a chance. And he was following the letter of the law and then he got fired. And dear old Ralph Nader, bless his heart, sued to reinstate this guy. And this guy lived out his career and never approved a single drug during his entire career. Now, there's a certain irony to this because one of the divisions he was in charge of was the renal drug division and he died of cancer. Kidney failure. The obituary in the Washington Post was, FDA official known for strict driving habits dies. But sometimes you can kill people because you don't act. Because for every year an IRB says, hey, why don't we just study this for another year? Why don't we take the summer off because this might not be safe? Hey, let's have another 2 or 3 years to study this stuff. Yeah, we can kill people through mistakes and we do kill people through mistakes and there are some bad actors out there. But the majority of people involved in drug discovery and in academic research are not bad apples. And every year that we stop this stuff and say, let's do this in 10 years or 12 years instead of doing it in 3 years. Well, look, I care if it's for hair loss, okay? But it really doesn't matter what I look like. If you're doing that for cancer, if you're doing that for gene therapy, if you're doing it for a whole series of other things, you may end up killing more people because you're being careful than you're saving. And we have to measure the cost of acting against the cost of not acting., and that gets lost in a lot of the ethical debates. Because it's very easy to say, "These are the bad people, these are the good people, we're just trying to protect you. Let's study this for another 5 years," without ever measuring the consequences of what you're doing when you do that. That's a really important part of ethics that gets lost in a lot of these debates, because it's easy to stereotype people.

So with that, we have a little less than 15 minutes. I would love to open this up to questions from the audience. I think there are microphones that are around the room. Does anyone have any questions?

[INAUDIBLE] genetically modified organisms in terms of feeding the world.

If we can't feed the world, we won't have the humanity or the biology to play around with. Yet here in the West, we seem obsessed with the— against GMOs. Yet where they're needed, where food is medicine to feed the world, they seem to be denied and prevented from being out there.

What's your view about GMOs?

I'm hearing from you today. So I think GMOs is a big word. And I think agriculture has mostly brought GMOs in as a producer trait. So it makes it easier for the farmer not to use as many pesticides. It makes it easy to grow in drought areas. It makes it easy to grow in— salt areas, and what that does is it makes the world easier for the farmer. But if you go into Whole Foods and it says, you know, genetically modified corn $1, all natural corn $1.25, a lot of people are buying the all natural corn even though the price is higher. Now, if you start to flip that and you can take strains of wild Italian broccoli and put it into food and say possible cancer preventing corn, $3, All natural corn, $1, right? Then when you start getting consumer-facing traits in foods, and you see a little bit of that with modified rice, but if you see more of that, then the acceptance is gonna be much higher of GMOs. And why am I pretty certain about that? Because a lot of the medicines all of you produce are GMOs. All biologics are GMOs by their nature. And you don't see a lot of bitching about, oh, I don't want something to cure my cancer because it's a GMO. No, right? And I think agriculture is going to flip on that. But you need to have more consumer-facing traits for people to accept it, either in price or in output and characteristics of the stuff.

I think we can probably hear you even if there's— Sure.

Jim Bowen, Syrus Research. It was wonderful hearing you. Philosophical question. You had discussed unnatural selection, the fact that we are pushing the boundaries of science in a way that we are changing what would be considered a normal evolutionary pathway. Do you think it would be fair to consider an alternative hypothesis is that we are simply participating in natural selection based on human beings, our brains evolving, the curiosity we have exhibited over— developed over millennia, that based on our scientific advancements, the way we're evolving, nature's giving us a push to say, hey, you better speed it up if you want to continue living on this planet or expanding. Or alternatively, if we don't apply, as you were saying, ethics, humility, wisdom in applying these technologies that we're following the alternate path, we're selecting against us, so eventually human beings will be extinct and perhaps the dolphins will be able to take over.

Yeah, I mean, we're going very fast. I mean, whether you call it natural or unnatural, humans are part of nature, but we're going at unprecedented speeds. Some of it is trial and error, but an awful lot of it also involves computers and human intelligence in planning for the future. We probably, as Juan says, we can make mistakes of omission. If we just do nothing at all, our planet and all the life on it will be destroyed by a variety of natural phenomenon. So that's another mandate that we have that all the other organisms on the planet are not even thinking about that particular problem.

So I'm reminded of that cartoon that says asteroids are nature's way of asking, how's your space program doing? Right? So if you don't have stuff to take out asteroids, you know you're going to die. And there has been no species as dominant on this planet planet since the entire planet was covered by blue-green sludge meters deep, right? I mean, the whole damn thing was covered by this gunk. No other species has had anywhere near the dominance that we've had or the control over other species. So there are people who say, "Well, that's completely natural." Well, no, it's not completely natural. No species has ever come close to being as dominant. Over what lives and dies on Earth. No species has ever guided what lives and dies on Earth close to us. I mean, the only rival at some points were viruses and plagues. But we are so much more powerful than any virus or any plague at taking out or creating species and saying, "I want 6 billion animals that I can eat. I want these kinds of flowers." I don't want this kind of stuff. And recognizing that is incredibly important, because if you don't recognize it, you don't apply the Pottery Barn rule: you break it, you own it. Right? And if you're doing this, you're also responsible for this. And you can't say, well, you know, that's nature. No, it's not. Right? And for good and for ill, Take responsibility for what you're doing and face it head-on. And by the way, I'm an optimistic curmudgeon, right? I don't want you to walk out of here thinking, "Oh my God, the world's gonna die." No, I think the world's gonna be a better place in 100 years, in 200 years, in 500 years. I wish I was here to see it. I don't think I will be, but this is a very cool time to be alive, especially in Boston.

And can I ask, who's— when you're saying own your responsibility, I mean, whose responsibility do you think it is? Like, who is the person that has to answer for how new advances are being developed and how they're being applied and implemented?

I don't think there's a more important corner on this planet than Vassar and Main Street. And I actually mean that literally. There isn't a place anywhere where you can walk through those 6 buildings and look at the future of the brain and the Whitehead and Novartis and the Coke and the Gates and the Stata. And about 1% of the global economy is gonna come out of that corner in terms of spinouts from folks like this. I don't think there's a place on the planet that has ever concentrated the ability to change life and AI and the internet and the future of all of us that looks anything like Boston. California is big, it's really important, but try walking from Berkeley to UCSF to Stanford. You've got 92 colleges and universities here, right? And people just don't understand because Boston doesn't like to brag. You go into this This parking lot right here, there aren't a lot of Ferraris and Maseratis in there because the currency isn't what do you got, it's what did you make, what did you learn, what have you found, what are you building. And that's a currency that comes out of wearing jeans. It doesn't come out of diamonds. You don't show up in Boston and say, "Hey, I'm a big guy. I'm a really powerful woman." No. You do what George just did. Doing some stuff in my lab, and that probably means he's on his way to a Nobel Prize. You know? Somebody here tells you, "I know a little bit about that," shut up and listen. Right? And we're really privileged to live here. This is one of the most powerful music clusters on the planet. Very few people know that. There's one competitor to Juilliard. It's Berklee. And it's sitting right next to the symphony and the conservatory and the pops. In 4 blocks, you've got one of the most powerful music clusters on the planet. The finance sector downtown. That's one of the most powerful finance sectors anywhere. But Abby Johnson walks into the hotel, you'd have no idea this is the most powerful woman in finance in the country.

Right?

And it's just a privilege to be here. This is a very cool spot.

Anybody else want to jump in?

Yeah, go ahead. Actually, I have the microphone. Hi, this is Christina Hartman from the EveryLife Foundation for Rare Diseases in Washington, D.C. So we represent the entire rare disease community, and 95% of our patient population still does not have access or an FDA-approved treatment in existence. A lot of our patients take therapies off-label, but there are still many who have absolutely nothing, and probably in part due to the bad beltway drivers, I'm sure, at the FDA. However, my own daughter was born recently with a rare genetic disorder. It took me a year to get a diagnosis and I live two blocks from the NIH, and they told me that that was actually fast. So one of the things I'd like to hear from you all is, you know, we clearly have a long way to go. It's great that we can consider creating designer babies, but for everyone in this room, I'd like to remind you that there's a good chance that one of your children or grandchildren could be born with a de novo pathogenic disorder. My daughter's was not inherited. It was just a random base pair that was swapped, leading to an amino acid change. A lot of our kids have these issues. Many of them have degenerative disorders, and they die before the age of 5. So given that this is still the current situation, you know, where do we go next? Are we going to focus on designer babies, and how much of that can you really control? Or are we going to help the kids what can we do for the kids who are right here right now who still desperately need therapies?

I think there are just— first of all, I wish your daughter the best, and I certainly hope there's something that someone in our community can do to help. I think there are a couple things that we have to hope happens as fast as possible. And one thing is that we get to situation in which all newborns are fully sequenced from stem to stern. I think that's coming. George can probably talk about, you know, what the time constant is, but it feels like it's probably within the next 5 to 10 years. And so— and that's not spot sequencing, it's not SNP, it's full stem-to-stern sequencing at high density to say what is your genetic inheritance. That's number one. Number two, we desperately need to increase the design-build-test, design-build-test cycle for therapeutics. And we especially need kinds of therapeutics— we need more— a lot of rare genetic disorders are loss of function because it's just a lot easier to lose a function than to gain a function. So we need a much faster design-build-test cycle for gain-of-function therapies. Right now we have only a few different ways of doing that, gene therapy being one. And I think there is now, fortunately, a major thrust in that area. But other types of medicines that have a rapid cycle are, for example, nucleic acid therapies. Therapeutics. So I think that's probably the best chance to accelerate the vista. Now, there's reason to be optimistic. If you look at spinal muscular atrophy, for example, I think largely through the efforts of Dinakar Singh and Lauren Eng, who founded the SMA Foundation, the time frame for identification of the genetic cause of a disease to actually getting not just one but two therapies out into the market was remarkably fast. And in that case, it was because the medicine is in fact a genetic medicine. It's an oligonucleotide therapeutic. I think there's reason to be optimistic. It's never going to be fast enough. But we are, as George mentioned, we are in a time of accelerating both understanding a time of acceleration of actionability on that biology.

I would just add, I'd be delighted to work with you on this, but the de novo mutations that act very quickly can do so much damage before the child is even born that you really have to do it early. I mean, you can have microcephaly, for example, that would be very hard to come come up with a drug that would fix that after birth. So one possibility would be universal IVF. That sounds a little strange because if you sequence them before you even implant them, that's the earliest you could possibly do it. And you could do whole genome sequencing and we're getting much— we're really quite good at predicting most of the very serious diseases, Mendelian diseases that you're talking about. You know, but the other possibility would be have something that's— that you don't have to do IVF, which is not that easy or convenient medically, but you could still detect it at the similar few-cell stage. Those would be my two suggestions for the most extreme de novo mutations.

[INAUDIBLE] So with that, I think we're actually out of time for this morning, but everyone could join me in thanking the panelists. This was really interesting.