The Genetic Revolution Has Begun - George Church on What Comes Next (#274)

Speaker 1 Where nature might make a few genetic changes in a million years, scientists today can make billions of changes in an afternoon.

Speaker 1 What happens when we can rewrite life itself and even design new materials that have never existed before?

Speaker 2 Hi everyone, I'm Lynn Toman and this is Three Takeaways. On Three Takeaways, I talk with some of the world's best thinkers, business leaders, writers, politicians, newsmakers, and scientists.

Speaker 2 Each episode ends with three key takeaways to help us understand the world and maybe even ourselves a little better.

Speaker 1 Today I'm excited to be with George Church, one of the most visionary scientists of our time.

Speaker 1 George is a Harvard geneticist, a pioneer of the Human Genome Project, and and one of the founders of synthetic biology.

Speaker 1 He's authored more than 700 scientific papers, holds over 150 patents, and has founded or co-founded more than 50 companies at the forefront of gene editing, genome sequencing, and regenerative medicine.

Speaker 1 His work helped lay the foundation for CRISPR, personal genomics, and even de-extinction, the idea of bringing back lost species like the woolly mammoth.

Speaker 1 Now he's exploring how biotechnology, artificial intelligence, and material science are converging to extend life, cure disease, and possibly even redefine what it means to be human. Welcome, George.

Speaker 1 It is a privilege to have you on three takeaways today.

Speaker 3 Thank you. It's great to be here.

Speaker 1 Thank you. George, what do you see as the greatest promise of biotechnology? Is it perfect health or is it something even more transformative?

Speaker 3 Transformation tends to be open-ended. So, you know, you discover fire and then you're not satisfied with fire.
You need to have an internal combustion engine and then you're not satisfied with that.

Speaker 3 You need to have a supersonic jet and so on. But let's take the next steps is what would be big things for biotech.
First of all, reversal of age-related diseases.

Speaker 3 So these will kill 90% of us, and they seem so hopeless that a lot of people don't even define it as a disease. You know, it's just inevitable.
But we seem to be making exponential progress on it.

Speaker 3 So that's one big thing for biotech. But beyond that is, as part of the aging thing, we can delay onset of cognitive decline.

Speaker 3 Beyond that, we can say, well, rather than wait and delay aging of cognitive decline, we could have cognitive enhancement, which is one one way of dealing with cognitive decline is to balance it out with enhancement.

Speaker 3 But probably

Speaker 3 biology could have a big impact on space travel. If for one thing, we can make incredibly tiny payloads, because out of just a nanogram of material comes a human being.

Speaker 3 So in principle, things that would be nearly impossible to do with the kind of giant payload you would need for having an entire population stay awake for thousands of years to get the alpha centauri you might be able to do with smaller packages.

Speaker 3 So those are three pretty big things that we could do.

Speaker 1 You've talked about the idea of escape velocity for aging, that we might be able to outpace decline. How close are we to that?

Speaker 3 Well, it's one of these things that we won't know how close we were until we pass that point. There's exponential basic technologies like reading and writing DNA.

Speaker 3 Those Those continue to be exponential, and all those are relevant to learning about and getting feedback on new cures. We also have exponentially growing knowledge of genes involved in aging

Speaker 3 and long-lived animals like bowhead whales that live 200 years, long-lived humans which live over 110 years. And we've accumulated a lot of that information.

Speaker 3 And so we have hypotheses that we're testing on the way to the clinic.

Speaker 3 So, for example, one of my companies, Rejuvenate Bio, Bio, has done two sets of three gene therapies that look very promising, that actually have a survival curve shifting to the right, that is to say, you know, extending life from the point of administration, maybe 50%.

Speaker 3 So these are ready for clinical trials. If they work, then I don't know if that'll get us escape velocity, but it'll get us the confidence that we need to scale up even more.

Speaker 3 And then I think it will directly lead to escape velocity within a decade or so. Now, part of the thing that I used to have a much more sober estimate of time, you know, like two decades.

Speaker 3 But the thing that's changed is we're now getting clinical trials approved and completed in as little as seven months.

Speaker 3 So I think that combined with all the technology that reduces toxicity and increases efficacy, I think we're going to see. you know, really a renaissance of therapeutics.

Speaker 1 So essentially then for people in their 40s, 50s, 60s, you believe that there might be enough treatments or therapeutics for aging that they might live considerably longer, that their decline might be outpaced by discoveries?

Speaker 3 Yeah, the ones that we've tested, we've tested in old animals. And even when you start the dosing at an age where half the animals have died of old age, the other half get their life extended by 50%.

Speaker 3 So

Speaker 3 that says maybe not even 60%, maybe 70 or 80-year-olds will get some advantage.

Speaker 3 And if they get enough advantage that they stop or reverse some of the processes, then they might make it to 90, and there'll be a whole new set of technologies.

Speaker 3 So I don't know what the cutoff age is for longevity, escape velocity, any more than I know when that will arrive.

Speaker 3 But it sure looks fast to me, just in the same way that sequencing improvements look fast to me.

Speaker 3 We made about a 20 million-fold improvement in cost and quality

Speaker 3 in less than a decade.

Speaker 1 You've explored something that sounds almost like science fiction, de-extinction of several species. Why try to bring back extinct species and what do you hope we'll learn?

Speaker 3 Well, so not everything we do is aimed at learning, even though I am a professor, but a lot of these engineering tasks is what we can do for humans or for society or for the planet.

Speaker 3 So the goal of de-extinction is to change the dialogue about endangered species and environments that are less than ideal for human considerations.

Speaker 3 I think that the skill set we developed there helps us think about restoring environments that are on the brink or have already gone over the brink.

Speaker 3 So for example, the Arctic used to be a much more fertile grasslands, fixed a lot of carbon. In fact, there's more fixed carbon in the Arctic than pretty much the rest of the world put together.

Speaker 3 All the rainforests have about one meter of topsoil, while the Arctic has 500 meters in places. So we'd like to restore that.
The Sahara Desert was a very fertile green area.

Speaker 3 One could restore part of that, retain some of the deserts, and then restore some of the grasslands. Both of those would have huge impacts on climate.

Speaker 3 But in the initial stages, it would just be restoring plants and animals, many of which we killed off.

Speaker 3 So for example, the part of the reason the Arctic is so impoverished is that we killed off all the mega herbivores, which completely disrupted the tree-to-grass ratio, for example.

Speaker 3 So that's some of the motivation for exploring it. But part of it is also just to get back to your learning point, is to learn how developmental biology works.

Speaker 3 How can we move an amazing trait from one animal to another one? Can you take a very favorable trait from one human and transfer it to another one through gene therapy, say?

Speaker 1 How do you see biology merging with engineering and material science? Are we at the beginning of a new era where biology becomes an engineering discipline?

Speaker 3 I think we're well into that era. And from a material science standpoint, biology is fantastic in at least two ways.

Speaker 3 One is that it can make materials that are atomically precise, and not just in some periodic way, like a salt crystal might be atomically precise, but it's kind of a boring repeat.

Speaker 3 Biology can make things that are incredibly complicated and atomically precise. And then the second thing that biology has that other fields of engineering haven't benefited from is evolution.

Speaker 3 Both ancient evolution, we have three billion years and 10 to the 20th milliliters of water worldwide. and soil.

Speaker 3 But we also have the ability to do evolution, accelerated evolution within our lifetimes.

Speaker 3 So those two forms of evolution, the one gives us raw materials, very sophisticated machines-like things that are atomically precise. And then the ability to accelerate evolution billion-fold gives us

Speaker 3 the ability to change that to new things that weren't under selection in the past.

Speaker 1 AI can now analyze biology data. Do you think AI could eventually not just analyze data, but actually design life?

Speaker 3 Well, we've used AI for many years now to design proteins, and those are finding their way into clinics. Now, that's not designing life with a capital L.

Speaker 3 We also are using AI to design genomes, and that will surely grow and create more diversity in the number of the kinds of genomes we can make.

Speaker 3 And then the genomes, of course, not only make single new proteins, but they can make whole systems of proteins. So I think we're well well into that era.

Speaker 3 We'll look back on this as being very primitive where we are now, but it's very definitively moving in the direction that you described of having AI design living systems.

Speaker 1 George, you've spent your career pushing the boundaries of what's possible. When you look ahead, what gives you the most optimism about where biotechnology and AI can take us?

Speaker 3 I think it's seeing things like the end of one baby KJ being cured in seven months from first discovery of this new genetic disease to a gene therapy solution.

Speaker 3 It's seeing how quickly and with shared vision we solve the COVID crisis, came up with drugs and vaccines. I think it's seeing kidneys getting transplanted from heavily engineered pigs into humans.

Speaker 3 I mean, I don't think we necessarily have the final answer on that, but there are people that have have escaped months of dialysis procedures, which they really hated. That's a big step.

Speaker 3 And the progress we've made on age-related diseases. I mean, at least the preclinical trials looked very promising.

Speaker 3 And I think that the low cost of gene therapies and the high specificity and being able to target specific tissues.

Speaker 3 All of that adds to the increased optimism for how we can direct biotechnology towards things that people care about.

Speaker 1 What do you hope will be possible in the next 10 or so years?

Speaker 3 10 years used to be

Speaker 3 just a start on clinical trials.

Speaker 3 Now, if we take seriously the possibility of getting clinical trials done in seven months for gene therapy of a baby and 11 months for COVID vaccines, I think in 10 years we could have very

Speaker 3 good solutions to diseases of poverty, like malaria and tuberculosis, sickle cell, and age-related diseases, which are killing us what I think is we're often in our prime, or we should be in our prime.

Speaker 3 In other words, we're extending youth so that we can both enjoy our families and enjoy our vocation, our jobs for many decades.

Speaker 1 And what worries you most?

Speaker 3 What worries me is that

Speaker 3 I think we're solving the inequitable distribution with things like vaccines, which where you can deliver it to everybody. Probably genetic genetic counseling is

Speaker 3 something that could be freely available. What worries me is that the inequity we have right now, certainly the huge inequity we have on people being born.

Speaker 3 Some people are born very, very healthy and they will be very healthy for their whole life just because of the lottery that they won. And then other people who die.

Speaker 3 as four-year-olds or as 10-year-olds or with great anxiety for the whole family and great cost to the community that supports them.

Speaker 3 I think if we can cure some of these severe Mendelian diseases cost-effectively, I think we can now we have the tools to do that. That would remove one of my concerns.

Speaker 3 And in particular, psychiatric disorders, that has a huge economic burden on the world. And so it would be nice to either give them the tools to cure themselves or

Speaker 3 in some other way deal with public health issues.

Speaker 1 George, what are the three takeaways you'd like to leave the audience with today?

Speaker 3 I think number one, we are a species that is almost everything in science and technology is exponential.

Speaker 3 Number two, we can apply that to diseases of poverty and diseases of aging, which will make us all healthier and cognitively healthier for many decades.

Speaker 3 And then third, we have an obligation to improve our environments, both for ourselves and other species.

Speaker 3 And that includes becoming a space-faring species, not to leave Earth, but to adapt to other places and have other places adapt to us.

Speaker 1 George, thank you so much. Thank you for your time today, for your research, and your many discoveries that are improving health for all of us.

Speaker 3 Thank you very much. It's really been a pleasure talking to you.

Speaker 2 If you're enjoying the podcast, and I really hope you are, please review us on Apple Podcasts or Spotify or wherever you get your podcasts. It really helps get the word out.

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