A (3:39)

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?

B (3:49)

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, those are 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 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. And so we have hypotheses that we're testing on the way to the clinic. So for example, one of my companies, Rejuvenate 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 extending life from the point of administration, maybe 50%. 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. 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. But the thing that's changed is we're now getting clinical trials approved and completed in as little as seven months. 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.

A (5:25)

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.

B (5:43)

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%. So that says maybe not even 60, maybe 70 or 80 year olds will get some advantage. 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. So I don't know what the cutoff age is for longevity, escape velocity, any more than I know when that will arrive. But it sure looks fast to me. Just in the same way that sequencing improvements look fast to me. We made about a 20 million fold improvement and cost and quality in a. You know, in less than a decade.

A (6:33)

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?

B (6:46)

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. And this. So the goal of de extinction is to change the dialogue about endangered species and environments that are less than ideal for human considerations. I think that the skill set we develop there helps us think about restoring environments that are on the brink or have already gone over the brink. 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. All the rainforests have about 1 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. 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. But in the initial stages, it would just be restoring plants and animals, many of which we killed off. 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. 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. 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?

A (8:33)

Say, 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?

B (8:46)

I think we're well into that era. And from a material science standpoint, biology is fantastic in at least two ways. One is that it can make materials that are atomically precise and not just in some periodic way, like salt crystal might be atomically precise, but it's kind of a boring repeat. 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. Both ancient evolution, we have 3 billion years and 10 to the 20 milliliters of water worldwide and soil. But we also have the ability to do evolution, accelerated evolution within our lifetimes. 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 the ability to change that to new things that weren't under selection in the past.

A (9:50)

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

B (10:01)

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. 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. 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 into that era. 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.

A (10:42)

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?

B (10:55)

I think it's seeing things like the n of one baby KJ being cured in seven months. From first discovery of this new genetic disease to gene therapy solution is seeing how quickly and with shared vision we solved the COVID crisis, came up with drugs and vaccines. I think it's seeing kidneys getting transplanted from heavily engineered pigs into into humans. I mean, I don't think we necessarily have the final answer on that. But you know, there are people that have escaped months of dialysis procedures which they really aided. That's a big step. And the progress we've made on age related diseases, I mean, at least the pre clinical trials look very promising. And I think that the low cost of gene therapies and the high specificity and being able to target specific tissues, all of that adds to the increased optimism for how we can direct biotechnology towards things that people care about.

A (11:59)

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

B (12:03)

10 years used to be, you know, just a start on clinical trials. Now if we take seriously the possibility of getting clinical trials done in seven months for gene therapy of a baby in 11 months, for Covid vaccines. I think in 10 years we could have very 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. In other words, we're extending youth so that we can both enjoy our families and enjoy our vocation, our jobs for many decades.

A (12:47)

And what worries you most?

B (12:49)

What worries me is that I think we're solving the inequitable distribution with things like vaccines which where you can deliver it to everybody. Probably genetic counseling is, you know, is 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, you know, 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 as 4 year olds or as 10 year olds or with great anxiety for the whole family and great cost to the community that supports them. I think if we can cure some of these severe Mendelian diseases cost effectively, and I think we can now we have the tools to do that. That would remove one of my concerns 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 some other way deal with public health issues.

A (13:57)

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

B (14:03)

I think number one, we are a species that is almost everything in science and technology is exponential. 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. And then third, we have an obligation to improve our environments both for ourselves and other species. 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.

A (14:40)

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.

B (14:50)

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

A (14:54)

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. If you're interested, you can also sign up for the Three Takeaways newsletter at 3takeaways.com, where you can also listened to previous episodes you can also follow us on LinkedIn, X, Instagram and Facebook. I'm Lynn Thoman and this is three takeaways. Thanks for listening.