A Bold Plan for De-Extinction: Mammoths, Colossal Founders, & More | Blazing Trails | Salesforce

All right, welcome to Blazing Trails. I'm Michael Revo from Salesforce Studios and today I'm excited to welcome the founders of one of the most interesting companies out there. It's called Colossal and it's founded by my guest, serial entrepreneurs and investor Ben Lamb. And world renowned geneticist and serial biotech founder and professor of genetics at Harvard Medical School, Dr. George Church. So Colossal is tackling the problem of extinction through a process called de extinction. And they're already in the process of bringing back the woolly mammoth. So we're going to learn why this is important and the impact it's going to have on the planet and all of us. So welcome Ben lamb and welcome Dr. George Church.

Hello.

Thanks for having us.

Okay, great. Dr. Church, let me kick it off with you. I just want to get some grounding in this idea of de extinction. I imagine a lot of folks, some have heard, some have not heard about this. Can you describe what it is?

Well, we're mainly focusing on de extinction of individual genes, not so much of species. That's an important distinction. We, we get some traits and the, and the traits will make it functional. And our goal is really to have a cold resistant elephant. And there have been many interbreeding of these animals, both the cold resistant and the non, over the millennia. And so we're making hybrids, just like they made hybrids themselves, somewhat, although we're using new tools. So de extinction is reading the, reading the old DNA into a computer, then using a computer to write the old DNA and then to recombine it with some of the tools that our lab and others have developed for editing genomes. And we can, we're getting better and better at making multiple edits and we just get closer and closer to our functional goal and, or something that has a lot of extinct alleles and variations on genes.

Got it. And so what's the impact of going back to some of these extinct genes or, you know, an extrapolation of that species? What's that going to do? Why do it?

Part of its diversity. We want to restore diversity and we want that diversity to extend around the globe wherever related genes might be found and back in time a million years, which is kind of the record right now for DNA in general and mammoth DNA in particular. We would. So diversity is one. Another one is adaptation to modern environments or adaptation to goals that we have like carbon sequestration. And we're not restricted to ancient DNA. It's not just about de extinction. We also have synthetic DNA that we can use in addition to modern and ancient. So we can make them, for example, virus resistant or better at handling certain natural toxins and TUS links. Those are three synthetic goals. So it's not restricted geographically in time or even in naturalness.

Ben, I wanted to talk about the sort of business side too. And we're going to come back to some of the science. But I heard you describe Colossal as a new type of venture, sort of looking beyond just value creation and at this new way of thinking about business. And we always say it salesforce, that business is the greatest platform for change. That's something that our founder, our co founder, Mark Benioff always talks about. And it seems like this really aligns with that. So can you tell me more about sort of the foundation of the, of the business model?

Yeah, I mean, we, people get really excited about the de extinction aspects, right? Like the mammoth, the thylacine, some of the animals that we've talked about. But you know, what we're excited about is the conservation aspects just as much. Right. And we think that there's an opportunity, when George and I started talking about building the business, to build a business that really is kind of the intersection of value creation, impact and impact being climate change, effects on conservation, and then also inspiration. And you know, we think that we can help, hopefully inspire by the work that we do here. We hope we can inspire the next generation, not just of conservationists, but biologists and geneticists of how, you know, maybe there's some little girl or a little boy that sees the work that we're doing, gets inspired by it and wants to then become, you know, that next groundbreaking geneticist like George and many others. And so really kind of the intersection of value creation, impact and inspiration was something that's really kind of core to kind of like our North Star as a company.

Ben, I'm curious from a business perspective and thinking about building this for the future, what do you see? What are some of those things that are going to happen in the future?

Yeah, I think that the technologies that we're developing, so we kind of have this like dual approach, right? So the technologies that we're developing on our path to the extinction that we can also apply to human healthcare, like multiplex editing, like additional computational biology tools for discovery, like protein engineering, all of those have massive applications to human healthcare. In addition to that though, we also have the opportunity that some of those tools have application to conservation. So our hope with the company is that all the technologies that we develop on the path to de extinction can be monetized for human healthcare. And, and we think that market's so big and the opportunities with some of these technologies are so vast that it will also help subsidize all of our conservation technologies. So everything that we develop from a conservation technology perspective, we want to be free to the world. And so an example of that is some of the artificial womb work that we're developing, or in the case of the thylacine, some of the exopouch work that we're developing for marsupials. We want that. We don't want to go sell marsupial pouches, but, but if that technology is critical for our de extinction paths, we want to be able to give that to conservationists so that they can use that and help existing small populations. And so whether it's artificial wombs or exopouches, or more advanced technologies in genomics like gametogenesis, we really want to advance these technologies that can be also applied to conservation. And so I think that George and I are 100% aligned on this dual use of not just bringing back these genes and creating these proxy species for what's gone extinct, but also applying it to human health care and then applying it to conservation and giving it to the conservation community. We feel really, really strongly about all of our technologies being able to be used for the conservation community.

It's interesting, it makes me think a little bit about some of the early Internet technology and so much open source, which is still, still exist today, around access to that technology. George, maybe you can talk about that a little bit around the structure of how we can equally spread this technology and folks are going to have access to it and be able to take advantage of it.

Yeah, this is very important to me. My lab has worked hard on reducing the cost of reading genomes, DNA sequencing and writing material, writing DNA vaccines, gene therapies, all getting them ultimate. And once you get it into the wild, then it has the ability to be free. So either extinction or de extinction. So we've collectively made smallpox extinct. And that's the gift that keeps on giving, is that no one has to pay a penny for upgrades in drugs or vaccines for smallpox because it's extinct. And the same thing is true for de extinction. If we get it back to the fertile grasslands that used to COVID 19 million square kilometers of Arctic, with much more diversity in animal life life and plant life, then that's something that's self propagating and spreads in the same way that rewilding of wolves had all kinds of downstream effects on the plants and the lakes and the beavers and so forth. So we want something sustainable, natural in a certain sense, but leverages technology in another sense.

Right. And, you know, I think you've probably been asked the question a lot about the ethics of it, you know, introducing, you know, ancient species, reintroducing species, and, you know, playing God, however we want to say that. But I'm curious what your perspective is on that in, in the effort of, you know, for good cause, that you're, that you're working.

Yeah, like, I feel like we, we play God, you know, every day when we either eradicate a species or, or we destroy an environment, or we pollute an environment, or we, or we change the atmosphere with carbon and manmade climate change. So I feel like we are constantly playing God on some level every day in the decisions that we make. And so I think that we have kind of this duty to, if we have these technologies that can help with species preservation and also with ecosystem restoration through the reintroduction of species and rewilding, you know, we, we have that duty, you know, to the planet, you know, that this is the only planet that we have right now. Right. And so unless Elon and other people get it right for other planets, it seems like that's a, a long way off. We really have this planet that we need to take care of, and we're going to lose up to 50% of biodiversity between now and 2050 if we don't do some of these things. And so, you know, we, we try to be really thoughtful from an ethics perspective. You know, George has an ethicist in his lab. We, we have ethicists at Colossal. We've also partnered with some of the largest conservation groups in the entire world when it comes to elephants and broader conservation as well. So we've really tried to be very thoughtful and transparent in our approach to this, and we welcome feedback. We've also started conversations with indigenous people groups as well as local governments and whatnot. So we've, even though the rewilding process is a very long process, we've already started those conversations, conversations now. And we've tried to do it in the most transparent way possible.

It makes me think about some of the massive projects that you've worked on, genetic sequencing, the human genome Project and many others. And thinking about technology leaps more generally, what Colossal is attempting to do right now is a huge leap. And just thinking about how do you approach these massive problems and sort of stay motivated and continue to work on them and continue to make progress? I mean, I think all of us have been challenged to Take on much smaller problems. So I'm curious about sort of what makes you tick with that?

Well, that's a great question. I think one of the things that makes it a little bit easier is our problems are blessed with exponential change, meaning that we don't have to wait that long. So and maybe even a little faster than most exponentials. So people have kind of gotten used to the exponential change in computers, so called Moore's law. But this has gone, you know, two to five to 10 times faster in many years. So that's one thing is you just kind of leverage that and now it doesn't happen by itself. You have to work on it. Some of these projects came in faster than we thought. So the genome project mostly was done in 10 years rather than 15. You could say that the final finishing of it hasn't been done yet, but the useful parts of it were already in place in a decade. We started the Brain initiative for new neurotechnologies. All of these things are on the order of billion dollar projects or multi billion, but they end up returning on that investment very quickly. I mean the return on investment sometimes can be a hundredfold even and pretty quickly. So that keeps us motivated and you know, that mixing in of, you know, real world applications where you see people in the clinic or in animals in the wild that benefit from it.

That.

Can happen quite quickly.

And so looking into the future, you know, 25 or 50 years at where synthetic biology is going to take us, specifically around disease and aging, what's the vision for that?

I love this question for George. I always love George's views on the future. It's my favorite. George and I sometimes still get as much done on calls as we want because we end up having these types of conversations. So George, what is your vision of the future?

The future is affected by visionary companies like Colossal. The spin offs are already happening. For example, computer and machine learning, aided design and construction is going to be key, not just to de extinction, but to synthetic biology. And synthetic biology is going to be key to manufacturing all kinds of devices ranging from computers to everything that's currently made with inorganic materials could be made with biologically inspired processes. And hopefully we will continue to make this accessible to everybody on the planet. That's one of the things that happens when you can radically reduce the price and then increase the speed is you can, you can, everybody and I think that should be a priority is eliminating diseases of poverty that could happen in much the same way as smallpox. Once you get diseases of poverty lowering, then you get A virtuous cycle where you get more free time and money to do for families to have more education, to have a little bit more money to invest in better health care. And it keeps going around. Also, aging is something that's very costly both emotionally and financially to the whole world. You get these people that have barely been trained like myself, you know, it took 68 years and I'm not quite fully trained yet. So now would not be a great time to retire at all. It's time to double the efforts. And I think we're getting much better at we've doubled the life expectancy, but I think we're getting that's also going exponential so that we can get aging reversal, which is the next big thing. And then finally I think space exploration is going to have a big biology component that we haven't really gotten around to as yet. But now we have all these new tools. So all of those and more in the next 25 years.

That's, it's amazing. And when right now with what Colossal is doing and I think this is interesting for our audience, which is building a business and a pilot platform where you can take the theoretical and bring it in and commercialize and make it operational is such an. It's a real challenge. And Ben, I'm curious to get your perspective on how do you think about that. What's your experience been there and bringing something like this to market and what can you share with that?

So my background has always been in building technology companies and mostly software and for the outside, the user interface software is mostly invisible and it's never bug free and it's always in the future. So I feel like building technology, software based companies building invisible things for the future has always been part of my career path. I completely believe in George's vision that synthetic biology will revolutionize everything. Not just species preservation and de extinction but, but I think that eventually we will be manufacturing things using synthetic biology that we currently are using hardware and silica and other things for. So I really do see a world where we talk about things like Smarter Cities. But for the most part what we're doing with Smarter Cities is we're putting more sensors and more electricity and less privacy. We're doing a lot of those types of things. I think there's a world where we actually engineer cities organically. And so I do think that synthetic biology and really the intersection of computational biology and AI and automation and synthetic biology will lead us to a much brighter future both on this planet and beyond. So I'm very, very passionate about what I think that synthetic biology can do. And I think that I was inspired by a lot of science fiction movies and science fiction books and comics over the years. And I think that we're at the doorstep of what can really be for humanity. I think we get a lot of doom and gloom in the media and whatnot, and we've got existential crises like wars and famine and poverty and climate change. But I do think that humanity has the tools and can come together to leverage synthetic biology and some of the tools that we're talking about developing in other sectors to combat these things. And so I'm very, very hopeful on that. And I'm excited to build a business that has the applications, has the downstream applications to help conservation as well as human health care. And I think that more and more companies like Colossal in the next decade will be formed with kind of that dual purpose.

And Ben, how are you thinking about this? I mean, you mentioned medicine as being a place where Colossal can focus. What are some of those solutions?

I think that molecule design and even protein engineering and other kind of entire categories you're starting to see come out of both computational biology and synthetic biology. I think that's going to continue to evolve. I think that what we've seen coming out of COVID with even the ramifications outside of a pure biology perspective, but even just the process that the FDA and others took to get vaccines out, I think all of that is also starting to be looked at and looking to be evolved. And so I think that there's entire new categories of drugs that are now coming out. And some of that's due to the pandemic, some of that's due to some of the breakthroughs in discoveries like CRISPR and others. And I also see a world like George where, where synthetic biology can help with things like food security. I think that we have the ability today to generate technologies that can feed entire families at home at an incredibly cheap cost. It's not going to be the high grade sushi or steak that you may get at some restaurant, but you can get plant based synthetic biology focused alternatives at home. And I think that whole wave is going to come. So I think there's huge opportunities around not just curing some of the diseases that are mostly in impoverished nations that George mentioned, as well as providing food security. But I think that there's a whole host of other applications that if we go back to engineering nature and working with nature, can be really transformative for the planet. And I think food security is going to be A big one that, you know, we, that we need to focus on, you know, in the next decade. And synthetic biology can be massively helpful there.

Yeah, absolutely. Okay, so to wrap up, I wanted to loop back to where you are with the de extinction rewilding process with the woolly mammoth. And what's the current status and what, what should we look for?

Yeah, I mean we, as George mentioned earlier, we, we focus on being radically trans.

Right.

And so we don't update people daily on every cell that's going on in the lab. But you know, we've stood up, you know, three labs, we have over 35 people working, you know, on just the mammoth project alone. You know, our original timeline was five to six years. We're still kind of marching towards that. We don't have kind of an update on that timeline, but we've established cell lines and we've, we've just. Earlier this year we just released, in partnership with the vertebrae genome project, the great work that they've done. We just released a full reference genome for the Asian elephant, you know, one of the most complete, you know, of its kind, which, you know, as we continue to do this work, we continue to publish everything, you know, publicly for science. And so we've made tremendous work on that. We've been, you know, continuing to do computational biology, computational analysis on all of the incredible work that George has done on the genes. And we're actually in the editing process. So we even have teams that are already doing editing cells as well as we have a team that's focused on embryology and somatic cell nucleotransfer in horses and rhinos right now getting ready for the elephant side. So all of the different kind of functional teams. What, what I think a lot of people don't realize when they think of the mammoth project is they think it's just cellular engineering. But to George's point earlier, it's AI engineers and software engineers, it's geneticists, it's animal husbandry experts, it's bioethicists, it's embryologists and people that are really great at fertility and editing cells and embryos. So we've really kind of built this cross functional team and right now we feel pretty confident on our progress that we're on track.

Well, when you think about all that work that's happening and Dr. Church, as you said earlier, the secondary effects, all the things that are kind of come out of it, it's an incredible platform that it seems like is being built through this process and it'll be exciting to see a woolly mammoth walking around.

Thank you.

Okay, fantastic. Well, this has been such an interesting conversation. We're just touching the service. There's so much here. So everybody go check out Colossal. Ben, what is the website?

It's just colossal dot com.

Okay. It's a great URL, Great, great company name and such an exciting project. So thank you so much for joining us. Ben, thanks for joining us today.

Thanks so much.

Yes. Thank you, Dr. Church.

Thank you.

That was Ben Lamb, CEO and founder of Colossal Biosciences and world renowned geneticist and professor of genetics at Harvard Medical School, Dr. George Church. To learn more about Salesforce, head over to salesforce.com customer360 and be sure to subscribe to Blazing Trails on your favorite podcast app or now on our YouTube channel, where our interviews are now on video. Blazing Trails is a production of Salesforce Studios, produced by Rachel Levin and engineered by Michelle Luong and Ryan Kleeman. I'm Michael Riva. Thanks for joining us.