#309 Jamie Metzl: Why Gene Editing Needs Governance Or We Lose Control

0:00I absolutely believe that the future of humans will include the genome editing of preimplanted human embryos that will be taken to term. So now what we need to be doing is laying the foundation, not just of the science, which isn't quite there yet, but also the legal, regulatory, governance, social norms, all the other pieces of societal infrastructure that are required to do this responsibly and not have it just turn into some kind of Nuremberg style human experimentation. even if the people who are getting these procedures aren't prisoners, but they're just kind of rich people trying to give their kids a leg up.

0:47Build the future of multi-agent software with Agency. That's A-G-N-T-C-Y. Now an open source Linux Foundation project, Agency is building the Internet of Agents, a collaborative layer where AI agents can discover, connect, and work across any framework. All the pieces engineers need to deploy multi-agent systems now belong to everyone who builds on agency, including robust identity and access management that ensures every agent is authenticated and trusted before interacting. Agency also provides opens standardized tools for agent discovery, seamless protocols for agent-to-agent communication, and modular components for scalable workflows.

1:44Collaborate with developers from Cisco, Dell Technologies, Google Cloud, Oracle, Red Hat, and more than 75 other supporting companies to build next generation AI infrastructure together. Agency is dropping code, specs and services, no strings attached. Visit agency.org to contribute. That's A-G-N-T-C-Y dot O-R-G. How did you get to writing about the future? Well, thanks so much, Craig. Greg, really a pleasure to be with you. My story in this stuff starts about 30 years ago. I was working on the National Security Council for then President Bill Clinton. And my boss at the time and current friend was Richard Clark, who at that time was obscure, later became very well known after 9-11 as kind of the Cassandra who had warned about everything but not been able to change the course of events.

2:53And Dick always used to say that if everyone in Washington is focusing on one thing, you can be sure there's something much more important that's being missed. And the key to efficacy in Washington and in life is to try to solve problems that other people don't see. And for him at the time, it was terrorism and cyber. And for me, 30 years ago, looking around the world, this convergence, what I now call superconvergence, of these incredible computer tools of machine learning, now we call AI, the tools of biotechnology, at that time the nascent genetics revolution, were all going to come together with profound implications for a whole lot of things.

3:34So I became very obsessive in my just self-learning about all of these issues. And when I was ready, I started writing articles about this issue and what it meant and what America could do to prepare. And then those articles got a lot of attention. And a member of Congress, Brad Sherman, called me up and said that he'd read them and he thought it was really important. He wanted to hold hearings based on what I'd written and asked if I'd be the lead witness and help him organize the hearings, which I did. And so I was doing a lot of speaking and writing on this topic, but I felt like I wasn't breaking through with the message to the broader audience I was trying to reach.

4:20And so earlier in my life, I had done my PhD on why the world failed to respond to the Cambodian genocide. And that was published as my first book. And then my first novel was exploring those same issues, but as stories so that people could absorb this history and in a more personal, intimate way. And so then that was when, with this other issue of these converging technology revolutions, I decided that I wanted to write sci-fi novels exploring all of these issues, but doing it in the context of stories. And that was the genesis of my two near-term sci-fi novels, Genesis Code and Eternal Sonata.

5:03And when I was at Genesis Code, it deals with human genetic engineering and Eternal Sonata, the science of hacking aging. And when I was on my book tours for those books, and I would explain the science to people in my way as someone who taught it all to myself, I could just see in people's eyes that they were suddenly getting that there was a very meaningful story that would have big implications for their lives. And suddenly they saw it. They saw themselves inside of those stories. And that was what made me feel I had to write a popular nonfiction book about the past, present, and future of humanity and certainly genetic modification and biotechnology and what that would mean for humans.

5:46And that led to Hacking Darwin, Genetic Engineering and the Future of Humanity. And that became a pretty big international bestseller. And when I was on my book tours for that book, I'd give a lot of talks and I never use notes. And I always just, so for that reason, my talks just change. Every time I give a talk, I'll incorporate new things. And I found my talks about human genetic engineering were just shifting because I would say, well, here's the story of human genetic engineering, but that's just a little piece of this much bigger story at the confluence of these exponential technological revolutions.

6:26And here's the even bigger story. And so that was what led me to start developing the thesis for what became my latest book, Superconvergence. And along the way, after Hack and Darwin was written, where I had predicted that the first CRISPR babies would be born in China, I'd predicted I had a list of five genes that would most likely be mutated. And one of the genes on my list was the one that the Chinese biophysicist Hu Zhongkui altered in 2018. After that, I was invited by Dr. Tedros, the director general of the WHO, to be a member of the World Health Organization Expert Advisory Committee on Human Genome Editing.

7:09And now after super convergence, now I've become a commissioner of the Lancet Commission on Precision Medicine, which is going to be working over the next three years to come up with a kind of a blueprint as much as possible for the future of health care at the intersection of these technologies. Precision medicine is kind of a shorthand, but it's really how do we think differently about the application of technology into health care. So basically my view is that there's so much happening and to understand it in a deep way, we really have to come at it from different angles. And certainly for me, kind of thinking like a science fiction writer is really important because increasingly we're living in a world that is moving at a pace of science fiction and feels to most of us like it has significant elements of science fiction.

8:04Yeah. And you focus on, within biotech, on gene editing, on genomics. But the super convergence is much broader than that. I mean, it's affecting everything from material science to fusion, you know, energy production and quantum mechanics. I mean, how wide and why did you decide to focus on genomics? So my net is pretty broad. I mean, my basic thesis is that the big story of this moment of life on Earth, not just human life, the life on Earth is this is the moment when one species suddenly developed the increasing ability to engineer novel intelligence and re-engineer life. And so that's going to have profound implications really across the board of everything.

9:07My particular focus was on the story of reengineering life. And so that has implications beyond just the life sciences, but it's obviously transformative for human health and healthcare, obviously transformative for agriculture, for energy now with the new age of biofuels, for advanced materials where we have new ways of developing the industrial products that we need for data storage. People think that there's this big division between computing and genetics, but DNA, of course, is the greatest information storage mechanism in history. It's much, much, better and more efficient in really every way than any kind of computing infrastructure that we have today.

10:01And so you could keep going broader and broader because even issues like quantum, which may feel to some people like they're totally dissociated from the life sciences, aren't dissociated at all. The quantum computers will be another tool to help us understand the world around us, including the living systems around us more deeply. That's what Richard and Feynman said that essentially the world isn't binary, the world is quantum. And so we need quantum analytics to better understand quantum systems. So I really see it as all of one piece. But when writing a book, I couldn't call the book the everything book.

10:41And so I tried to bind it as the intersection AI genetics and biotech. And I mean, there are so many ways we could go in this conversation. But let's focus on the CRISPR babies. Yeah. And because that seems to have come back. I mean, MIT had He Jiankui, you know, hosted him for a while and wrote a lot about those interactions. and then his supposed wife, it's a little unclear, Cathy Thier, as a startup now that's focused on gene editing to prevent hereditary diseases or genetic diseases. Why do you think it's coming? Well, you mentioned in the book that there was a long debate about IVF in vitro fertilization, and it took a long time for people to accept that as ethical and normal.

12:01Do you think there will be that same trajectory with gene editing of embryos? I absolutely do, but that doesn't mean that anything goes or should go right now. The reason why I've called He Jung Kuei every bad name in the book, a rogue, a lout, a scoundrel, is because I think that what he did was so phenomenally unethical. And not only that, by racing to be first without any regard to the basic underlying ethics or what's good for humanity or science solely for financial and nationalist reasons, as far as I can tell, he just basically undermined this entire field. So I absolutely believe that the future of humans will include the genome editing of pre-implanted human embryos that will be taken to TURP.

13:06And that will happen. I believe it will happen in the future. But I'm also, as I mentioned, I was a member of the WHO Expert Advisory Committee on Human Genome Editing, and I 100 % stand by our position that we humans aren't ready for doing that now. And so now what we need to be doing is laying the foundation, not just of the science, which isn't quite there yet, but also the legal, regulatory, governance, social norms, all the other pieces of societal infrastructure that are required to do this responsibly and not have it just turn into some kind of Nuremberg-style human experimentation. even if the people who are getting these procedures aren't prisoners, but they're just kind of rich people trying to give their kids a leg up.

14:03Yeah. But again, on the IVF debate, it was a little different because the outcome wasn't debated or the future wasn't debated as much as just the fact that there are religious and societal norms that were being broken. In gene editing, there's a real question once you have heritable mutations in the dean or edits in the gene, in the genome, what that could mean further down the line. Or as we all know, genes are not as discreet as you would like to think. So editing a gene may have one positive effect, but you don't see what negative effects it may have. Yeah, that's exactly right. We understand such a tiny percentage of the full complexity of human biology.

15:15And that's why when we're thinking about making one very specific change, changing a single mutated nucleotide from abnormal to more normal, especially if the abnormal mutation has the potential to be highly deadly. You know, at least that's a little clearer because if you know that somebody has a mutation that's going to cause Huntington's disease or some other deadly disorder, and you can change that. And of all the ways of addressing that, one option is wait till a child is born and treat it somatically. And another option is fetal surgery. And a third option in very limited cases may be editing the pre-implanted embryo.

16:02So in that third option, if we're saying we're going to make this single change that we're pretty confident is going to change a painful five-year life to a relatively normal 90 or 100-year life, then the cost-benefit analysis may be justified. What He Jiankui was doing had nothing to do with treating some kind of disease. What he was trying to do was to give these future children enhanced resistance to HIV at some point later in life. And it was totally unnecessary and unethical. And the risk clearly wasn't worth the reward. I thought in Ho's case, the intent was to develop a therapy for the children of HIV positive parents.

16:58No, it wasn't a therapy. So it was for children who had one parent who was already infected with HIV. But there's very, very simple things to do, for example, when it's the father called sperm washing. And so it's very easy to make sure that a father with HIV won't pass it to their children. So if it had been, if that first case had been carried out very openly, very transparently, very collaboratively, and it was addressing something, a single gene mutation disorder that otherwise would have been deadly to the child and there were no other alternatives, that would have been a great use case. This was very different for them.

17:53yeah although you know in this kind of stuff there's always a maverick that yeah that that upsets a lot of people but he they do kind of a break open a pathway that then others follow yeah so but this was the opposite because i think that maverick needs if the first step is a responsible, collaborative, constructive step, then that opens the door. So this Chinese effort, I think, actually did more harm than good to the idea of that at some point we would be able to edit the pre-implanted embryos of potential future humans. And so I think this was an anti - Maverick, even though I'm a big believer in Mavericks.

18:46But I should say Hu himself, his big heroes were Steptoe and Edwards, the guys who had innovated for IVF itself. And that's what he was saying is, I'm going to bring glory to China and win the Nobel Prize just like these guys. So I'm a big believer in Mavericks, but that doesn't mean every Maverick and everyone doing something calling themselves a maverick is is doing the right thing and i very much think that ho was not doing the right thing could i imagine a different kind of maverick doing this at some point in the future i can yeah why do you think it's come back uh i mean with uh kathy tia uh and i've forgotten that manhattan yeah she has a sort of a nod to the manhattan project in there um and there's um but there's some other startups i've seen i mean suddenly it's it's in the wind again why do you think that is yeah you're exactly right it's in the wind again there's this is i think his name is brian armstrong and he has a thing called the gattaca stack which is it just highlights what's so i don't know we can swear on this podcast so fucked up about all of this so this is we're talking about life and i think that you know humans were naturally hubristic species coming up with all this crazy stuff.

20:15I mean, squirrels haven't come up with space travel. They haven't come up with all. I mean, humans are nuts by definition. That's why we're here, because we have this diversity and we have all these risk takers. And when you see, I don't know if you saw the, I can't remember what it's called, Free Solo film about Alex Honhold, the guy who climbed El Capitan without any ropes. And they did this brain scan and it turned out that he just didn't have like his brain didn't light up for fear. And so this, you know, clinging to the side of a cliff, whatever, 600 feet in the air was just like you and I being here on this podcast.

20:57So we have a lot of diversity in humans And it's great that we have these kinds of risk takers. But there's a reason why we have societies and cultures to try to say, well, here are the risks that we want and here are the risks that we don't want. We don't want some individual person saying, you know, I'm going to start a war with some adversary just on my own or I'm going to do experiments in my basement that have the potential to cause a global pandemic killing billions of people. So it's always a balance, but I definitely think that we're in this hubristic moment. Definitely the message to the tech community has been that this is a no-holes-barred moment, which is a real shift between what was happening with the Biden administration here in the United States and what's happening with the Trump administration.

21:47And it's an exciting moment. And I get and I frankly share the optimism that all of these technologies can and will be applied beneficially to to humans. but I just think that a lot of people who are involved in this don't appreciate the full complexity of biology that it just seems to a lot of people who have been socialized in AI and computer tech that biology is just a system like that maybe in some ultimate cosmic way it is but biology is just much more it's a system of systems and so it's not just genetics humans aren't just genetics on stilts. We have many different dynamic interactive systems.

22:34We understand them very, very poorly. I'd say if understanding the full complexity of human biology is 100 and understanding nothing is zero, we're at three or four, meaning three or four percent understanding of all of biology, even including our own. And so it just seems like, change this, change that, and you'll get this outcome. Change this one gene and maybe you'll have a smarter kid. We have no clue how many genes say something about intelligence or, as you said before, a vigistic complexity. It's not one gene, one task. This is a very, very complex system, which doesn't mean we can't manipulate it.

23:12We've been manipulating complex systems for the last million years, at least. It just means that we need to balance our hubris with some element of humility and some sense of societal interests. Yeah, and that's interesting when you say people who have been socialized with AI, and even though it's not deterministic and are comfortable with it, and don't understand the complexities of biology. I see that a lot in the discussions of AI becoming conscious. Yep. Whether AI could become conscious. I mean, consciousness. I had Stuart Hamroff. He's the guy that wrote the book with Roger Penrose about the potential for quantum effects to be the link between biology and consciousness.

24:20which he sees in this kind of panpsychic view as a property of the universe. But I mean, he points out, and a lot of people don't understand, he calls the AI view cartoon neurons, you know, these neurons that are either on or off. but consciousness there's all kinds of other things happening there are different brain structures there's hormones there's yeah yeah everything else that contributes so yeah because ai has has made people look at complex systems in in a different way And that's normal. In a lot of our technological history, certainly since the dawn of industrialization, with every technology innovation, we always think, oh, humans are just like that.

25:26Humans are whatever. Whatever. And so now this HBO, I'm sorry, Netflix film, Frankenstein is that it reminds me it was like the early days of the industrialization and humans are electricity. And if you plug the electricity and you channel lightning, you can make a human. And with every one of these, we have a metaphor. Humans are locomotives or humans are whatever. And that's why, for me, it's why I write both fiction and nonfiction, because I think fiction forces you to stay plugged in to a recognition of the full and unknown complexity of humans and of life. Yeah. But when you say that gene editing, for example, is something to look forward to, but there have to be all of these regulatory and ethical structures built up before we get to that point.

26:30But that's not how the world works. I don't think it needs to be built up before, but I think that basically the science isn't ready. The science isn't at a level of efficacy to do this responsibly enough that we could feel justified taking a risk with another human, having it not be, as I said before, a Nuremberg-level human experimentation. I think we'll get there. And now we have new base editing and prime editing and less aggressive and more focused ways of doing this. So there's a lot of progress that's being made. So I don't think it's I'm not saying that we have to have everything in place and then move forward because that's obviously never going to happen.

27:22But while we're waiting for the science to advance, we really need to be investing similar amounts of energy, not just in regulation, but in governance. And governance is what happens at all levels of society, not just at the level of governance. Yeah. Where do you think the, I mean, I haven't looked at this as closely. Where do you think the progress is being made? Is it at university research labs or do startups like Kathy Tiaz and these others play a role in pushing the field forward? Well, certainly both do. And what I would differentiate, so certainly university research labs across the board.

28:08And then there are the gene editing companies that aren't doing pre-implanted human embryos. I mean, that's a tiny, tiny, tiny fraction. But there's a lot of companies that are doing great work on gene therapies. I mean, we're at the beginning of really of a new age of gene therapy. So you look at the mRNA vaccines, which were thinking differently about how to deliver instructions to the cell using the mRNA carried to our cells through lipid nanoparticles. There's huge progress that's being made in those areas. In the field of editing the pre-implanted human embryos, there are a lot of gonzo startups, certainly the ones who are doing the editing.

28:55There's other fields. I mean, I'm on the scientific advisory board for a company called Genomic Prediction, which is doing polygenic risk scoring for pre-implanted embryos. And that's a little bit different. That's saying, well, you have 10 different pre-implanted embryos and you want to pick which one to implant in the mother. the way that it's done traditionally meaning most of the time now is you have an embryologist who looks under a microscope and says that that one looks good that one looks whatever whatever it is fluffy healthy and and there's no there's no really way of testing those other nine so it's all just well i have an embryologist who seems like a nice person and they have a lot of experience and and maybe that's a good way i mean i think i'm you know i was the keynote speaker for their International Embryologist Association.

29:42And I've had a lot of conversations. And I actually do think it's meaningful to have an experienced embryologist who's just looking under a microscope and says, you know, I just feel based on 30 years of doing this, that this embryo looks like it's pretty healthy. And I think that's not nothing, as we say in Missouri, where I'm originally from. But being able to extract a few cells from an early stage pre-implanted embryo, after about five or six days. And then to sequence those cells for the 10 different embryos, you can actually get a lot of potentially highly relevant information. And so that's one thing.

30:23I'm much more optimistic in the nearer term about screening embryos smartly during IVF than I am about editing those embryos. Even though I do think that in the future, we will both screen, we'll screen, and then we'll do relatively small numbers of edits. There are people who I respect, like George Church, who are saying we can really scale up editing. But again, we run into the complexity problem. But if we did screening and we had one or two embryos that seem optimal based on that, and there were one or two very discrete changes, like changing a likely disease state to a likely non-disease state, I think that is probably where we're going.

31:08Yeah. You know, I've spoken to a number of people on this podcast about longevity studies and longevity strategies. And one thing I always ask, and it applies to this too, if we optimize human life so that we all live much longer as collectively, not only individually. Isn't that kind of, I mean, how does the world feed and clothe and provide power to that increased population? I mean, it's a little, we're sort of, you're younger than me, but I'm sure you remember Lester Brown, who was predicting, this is in the 70s, 60s, 70s, predicting that the population growth, we were going to run out of food and there were going to be wars over water and all this stuff.

32:16And in fact, you know, yeah. We may get our wars over over water, but it's a great question. And, you know, I write about this topic extensively and I give tons of keynotes to whether it's the health medicine associations or even to the biohackers, although I don't consider myself a biohacker. And what I will say is you framed it right because the right answer is how do we increase average lifespan? and we don't need any science, any new science in order to do that. I think that's the ethical question because we know the people in Japan are living on average to about 85. Here in the United States, we're living to on average 80.

33:06And there are people in places in Africa and elsewhere who are living until their mid-40s. And there are people in our societies, we're both in greater New York area. I mean, there are people who in our community who have much shorter expected lifespans than either you or I. So everybody should be saying, how do we increase average lifespan? And if we do that, we will just unlock tremendous potential everywhere. I mean, that right now, if we had a health in the United States, if everybody was healthier, if everybody was living a life geared towards living until they're 80 and 85, which means they're eating healthy diets and they're exercising and they aren't exposed to all kinds of environmental toxins.

33:53I think that would be fantastic. And there are a lot of people and a lot of people who have their own podcasts who are deeply involved with the issue of the science of aging, who have very high level credentials for well-established institutions. And a lot of these people are total bullshitters selling snake oil because the things that they are selling are these interventions that may work in mice and roundworms and fruit flies, but we have no idea whether they would work in humans or not, or could even cause harm. And so there's this whole feel that influencers like Brian Johnson with, I like Brian, but this don't die movement is preposterous idiocy.

34:50Everybody is going to die. It's just part of the natural order of things, and suggesting otherwise is just lying. And I can't imagine anybody believes that humans are are not going to die. If you want to live forever, order a bunch of plastic wear from Amazon and just keep throwing it out the window. That can be your legacy. Or maybe write a book or have kids and have them have kids down the line. And so I do think, though, that there'll be huge benefits for humans extending our health space. We'll save a lot of money. Humans, it's not like there's some limited amount of innovation that's possible to us.