Best New Ideas in Money

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George Church: The initial challenge is deciding which genes to change that would actually impact cold resistance. Step one is picking the genetic changes to make.

Stephanie Kelton: Welcome to the Best New Ideas In Money, a podcast for MarketWatch. I'm Stephanie Kelton. I'm an economist and a professor of economics and public policy at Stony Brook University.

James Rogers: And I'm James Rogers, a financial columnist at MarketWatch.

Stephanie Kelton: Each week, we explore innovations in economics, finance, technology, and policy that rethink the way we live, work, spend, save, and invest.

James Rogers: Stephanie, do you remember the first time you saw the movie Jurassic Park?

Stephanie Kelton: I remember seeing it, for sure. I don't remember exactly where I was, but I don't think I'll ever forget that movie.

James Rogers: Yeah, for me, it was quite a long time ago. This summer is actually the 30th anniversary of that blockbuster film.

Speaker 4: There it is.

Speaker 5: Welcome to Jurassic Park.

Speaker 6: We have made living, biological...

James Rogers: In case you need a refresher, in the movie, Jurassic Park is an actual park, a theme park on an island, the main attraction, dinosaurs which have been cloned. Scientists take dinosaur blood from an ancient mosquito trapped in amber and, with the DNA, bring back all kinds of dinos like the velociraptor, triceratops, and everyone's favorite, the tyrannosaurus rex. 30 years after the film's release, we don't have any dinosaurs roaming the earth, but one thing's for certain: major advances have been made in what it takes to edit DNA in all kinds of species.

George Church: Gene editing is a way of changing precise points in your genome that encodes all your bodily functions and then seeing what the effects are. And my particular inclination is to change multiple things at once, sometimes called multiplex genome editing.

James Rogers: That's George Church.

George Church: I am a professor at Harvard Medical School and at MIT focusing on biotechnology development, including new methods for reading DNA and writing DNA and then, almost anything you can make using DNA, including chemicals, organisms, ecosystems, organs, mostly for biomedical but a little bit for veterinarian agriculture.

Stephanie Kelton: We'll get more in-depth on some of those applications in a minute. But first, a little bit more background on Church. In the field of genomics, George Church is considered one of the founding fathers. Back in 1984, he helped start the Human Genome Project, a $3 billion international research collaboration to make the first sequence of the human genome. By 2003, the project was declared a success when it accounted for more than 90% of the human genome.

James Rogers: He's also an entrepreneur. The Church lab at Harvard has been involved in the creation of about 50 biotech companies. The lab has also done work with gene editing technologies, including CRISPR-Cas9. It works something like this: you cut a DNA sequence at a certain point and then add or delete more DNA.

George Church: We started doing that in 2009, and CRISPR is one of many ways that we've used since then. And there are ways of moving in big pieces of DNA, which are not CRISPR. There are ways of making very precise edits, which predate CRISPR, but they're all part of this more general genome engineering that we use from things ranging from reversal of age-related disease to making hybrid species humanized organs for transplant and so on.

Stephanie Kelton: Recently, Church has gotten more involved with those applications through a new venture, a company called Colossal Laboratories and Biosciences. Founded by Church and Ben Lam, a tech entrepreneur, the company aims to use CRISPR and other advances in gene editing technology to, as they put it, jumpstart nature's ancestral heartbeat. We'll unpack what that means in a minute. First, here's how Church got involved.

George Church: So Colossal was unexpected, I have to say. I had been musing about extinct genes and injecting diversity into modern endangered animals, in particular elephants, since about 2006, when a journalist asked me a probing, insightful question. But I hadn't really thought that I could get it funded. It just seemed like it didn't quite fit with National Institute of Health. It didn't seem to fit with a lot of government programs or even philanthropic interests.

James Rogers: Then, Church says Ben Lam approached him about a topic he had interest in, de-extinction, which is why we had Jurassic Park on the brain at the top of the show. De-extinction would mean using advanced cloning and gene editing technologies to bring back extinct species.

George Church: There is a de-extinction component; there is an endangered species component; but probably the main component that investors are interested in is in technology development. I mean, that's what my lab mainly does, and this is a stimulus challenge project which is creating a lot of new technologies on computational synthetic biology and developmental biology and reproductive technologies that would be valuable not just to the conservation community but for the medical community with spinoffs. One of the core technologies that we need for Colossal that I think could be broadly used is multiplex editing, being able to make multiple changes in the genome, not just one at a time. Most of the people in the world are quite happy to make one or two changes, but for Colossal, we make hundreds.

Stephanie Kelton: Church has already done a lot of work in multiplex editing. One example is a startup he co-founded, eGenesis. The company is working to address the transplantable organ shortage. Their solution: improving xenotransplantation. That's where there's a transplant from one species to another. eGenesis is harnessing gene editing to make pig organs more compatible with human needs.

George Church: We've engineered pig genomes in 69 different places to be more suitable for transplantation of organs for humans in need, changes that make them more immune compatible, less likely to throw off pig viruses that could infect human cells and evolve. So that's kind of de-risks is knowing that we can make 69 stable mutations in pigs and then they grow normally, produce organs that are already showing up to two-year survival in preclinical trials. So dramatic examples are in abundance.

James Rogers: Also in abundance, a question surrounding the ethics of gene editing, which we'll get to later in the show. It almost goes without saying this type of work takes a, well, colossal amount of money. When it comes to Colossal's projects, Church says Ben Lam is up to the task.

George Church: He went out to pay us $3 million to support it, and not long after that, he had raised a quarter of a billion dollars, and now we have adequate funding, I think, to achieve even his fairly aggressive goals.

James Rogers: We'll get to the specifics of those goals a bit later in the show. First, let's hear about how de-extinction can help benefit an ecosystem.

George Church: There have been thousands of so-called rewilding that illustrate how important it is when species disappear and reappear. Thousands of successful rewilding, most of them fairly recent within the last decade or so. Probably the most famous and well established one is the restoring wolves to Yellowstone Park after 70 years being missing.

Stephanie Kelton: By the end of the 1920s, gray wolves had been hunted to the point of eradication in Yellowstone National Park. In 1995, biologists in Yellowstone brought eight Canadian wolves to the park.

George Church: What happened is the various herbivores, like deer, were attacking the trees, like willows, so much that they didn't grow to beyond little shrubs. And then, the restoring of the wolves didn't really greatly decrease the deer population; it got them away from the willows, and the willows grew to full size. The beavers could now use them, and beavers started doing their thing. They changed the aquatic landscape of the park, restoring all kinds of species that had been missing, fish and waterfowl. And so that's how one species missing decreased the diversity and the vitality of the park and then restored it.

Stephanie Kelton: And this goes beyond Yellowstone.

George Church: Another example is in the Arctic, where probably some combination of human and other forces eliminated most of the large herbivores in the Arctic, and it caused a huge change from grasslands to trees, which is estimated by ecologists to have greatly diminished the diversity of the animal and plant populations. And furthermore, it's endangered the whole world because it's a tremendous source now of greenhouse gases being released at an alarming rate because the tree-to-grass ratio results in more warming, less photosynthesis, less trapping of the world's largest, arguably the largest, density of carbon. Anyway, so that's the environment that we're trying to restore, just as the wolves restored Yellowstone.

James Rogers: Coming up: we take a look at Colossal's first foray in de-extinction. Plus, how might advances in gene editing apply to improving human life? That's after the break.

Stephanie Kelton: Welcome back to the Best New Ideas in Money. Before the break, we learned about the work of George Church, a geneticist and professor at Harvard and MIT. He's also a co-founder at Colossal, a new company that wants to use gene editing technologies to potentially bring back extinct species.

James Rogers: Colossal's launch project is a big one. Here's how they put it, bold and all caps, on their website: Bringing back the wooly mammoth within the next five years. Now, suffice it to say, Stephanie, neither of us are scientists, so we wanted to run that characterization by George Church.

George Church: So we're not technically bringing back the wooly mammoth initially. We're not saying we couldn't do it; we're just saying that we're starting with a proxy, which is a cold-resistant elephant, which would help restore the grass-to-tree ratio which was initially there and restore the species. Analogous to what I was saying with wolves and Yellowstone, this doesn't require an exact copy of the mammoth. In fact, we think we could improve on both the modern elephant and the ancient mammoths in the sense that they might need natural protection from poachers in the form of reduced tusk size, which tends to discourage poachers. They do need resistance from a killer virus called EEHV; it's killing about 25% of the newborns at time of weaning. So those are two examples of things which would not necessarily be present in ancient or modern species. So we're not limited to any particular herd. So we can gather diversity from all over the world going back 2 million years is the oldest DNA we can get. So then the goal is to bring back the first engineered elephant calf in six years. That won't necessarily have all the traits that we want, but it will be a breakthrough, just like the heavily engineered 69 mutations in pigs.

Stephanie Kelton: Okay, so not exactly the wooly mammoth, but making a cold-resistant elephant isn't without its share of hurdles either.

George Church: I would say the initial challenge is deciding which genes to change that would maximally impact cold resistance. And to get to that point, we and the whole community has sequenced dozens, maybe 50 or more, modern elephants and ancient elephants, mammoths, and compared those computationally. So step one is picking the genetic changes to make. Step two is we need ways of testing the genetic changes for their impact and potential unintended consequences, some of which we might be able to do in simpler species, some of which we can do during fetal development.

Stephanie Kelton: The third challenge, Church says, is somewhat optional. The first milestone in the project is to make an engineered animal in six years. That can be done with nuclear transfer and surrogate development of the engineered calf, similar to what has already been done in pigs. Church says an alternative that could allow for more tests would be having extrauterine development of embryos.

George Church: That's routine in almost all species of vertebrates except for mammals. And in mammals, there's been a lot of breakthroughs recently due to development from in vitro fertilization forward and from preemies backwards. Both of those are human needs, but they have implication for being able to do this in a veterinary setting as well.

James Rogers: But it's not just the challenges ahead that the Colossal team has to consider. When it comes to de-extinction, some have raised ethical questions about early species suffering and dying in the initial stages of technology or about an engineered animal's ability to survive in the wild. We asked Church how he responds to those concerns.

George Church: Well, I raised a lot of those concerns myself, as I do for all the technologies that we develop in our lab. Try to recruit people to think about unintended consequences way in advance. And I would say this is still way in advance. In terms of survival in the wild, there are at least three nature reserves that have elephants in very cold climates, where, in the winter, they do seem to enjoy, at least for short periods of time, the snow; they will break through the ice and swim in the frigid water. And you can set up a barn in which they can freely go in and out, and you can assess just how much they like the cold without being coercive about it. Right now, a huge fraction of the Asian elephants are in tight quarters with humans where there's a bit of conflict, them trampling farm land and so forth. So I think we're very dedicated to making their life more pleasant and extending the range that they can occupy. It's definitely worth careful modeling and studying the genetic engineering of other animals to see how they do, and, increasingly, a lot of genetic engineering where we can assess possible unintended consequence.

Stephanie Kelton: In addition to hoping to increase the potential benefits to ecosystems and species, Church is also optimistic about the ways de-extinction may impact humans.

George Church: We hope to provide a general set of tools that will enable other groups to do a variety of species, but initially, at least my group, is focusing on the ones where they not only restore diversity to an endangered species but they help restore environments that would be valuable for human needs, like reducing climate change.

James Rogers: Throughout his career, there's a through line in Church's work. It's been revolutionary. I asked him, "What type of things do you think will be said about this period of research, and what do you think your legacy will be?"

George Church: I think this era will be remembered as a era of exponential technologies. I don't know if there will be the same level of exponentials in the future. Maybe. I've been surrounded, embedded and contributed to these exponentials in computing and in biotechnology where sometimes you get a tenfold improvement in one year. And a lot of things we work on are basic enabling technologies. So rather than making a particular widget that goes in your carburetor or making things that can be used in a whole variety of fields, and so it's that exponential rate, I think, will probably be the thing that's remembered more than any particular technology.

Stephanie Kelton: Thanks for listening to the Best New Ideas in Money. You can subscribe to the show wherever you get your podcasts. If you like what you heard, please leave us a rating or review. And if you have ideas for future episodes, drop us a line at bestnewideasinmoney@marketwatch.com. Thanks to George Church. To learn more about new ideas in technology, head to marketwatch.com. I'm Stephanie Kelton.

James Rogers: And I'm James Rogers. The Best New Ideas in Money is a podcast from MarketWatch. The producers are Michael McDowell, Mette Lutzhoft, and Katie Ferguson, who also mixed this episode. Melissa Haggerty is the executive producer. Tim Roston was our newsroom editor on this episode. The Best New Ideas In Money theme was composed by Sam Retzer. Stephanie Kelton is an economist and a professor of economics and public policy at Stony Brook University and not part of the MarketWatch Newsroom. We'll be back next week with another new idea.