That means endowing Asian elephants with the long hair and cold resistance of a mammoth and making facsimile dodos spring forth from chicken eggs.
For every species that’s a candidate for de-extinction, there are different technical and ethical and ecological challenges associated with them.
Being able to take the helm of science at Colossal… it’s way outside of the scope of anything that I would have been able to accomplish as an individual academic.
Shapiro: That’s also something that I’m really not in a position to comment on.
Shapiro: De-extinction is a moonshot, right?
There is a moonshot that says, “We want to create a mammoth.” Well, what do we need to make a mammoth?
Dodos became extinct because they’re a flightless bird that lays a single egg in a nest on the ground.
Shapiro: It’s here, on my arm.
In recent years, Colossal Biosciences has made headlines for its “de-extinction” efforts, revealing plans to bring back the woolly mammoth, the Tasmanian tiger, and most recently, the dodo bird. Along the way, the company developed a toolkit for bioengineering, which attracted investment from organizations like In-Q-Tel, a venture capital firm funded by the CIA. To aid it in its mission to witness these living replicas of extinct species roam the planet, Colossal has also assembled an impressive team of geneticists, among them prominent paleogeneticist Beth Shapiro.
Shapiro, the author of Life As We Made It (2021) and How to Clone a Mammoth: The Science of De-Extinction (2015), increased her role with the company last month from advisor to chief science officer.
Although it is impossible to recreate an exact replica of an extinct animal, scientists believe they will be able to (to borrow a phrase from Moneyball) recreate the species as a whole. This entails giving Asian elephants the mammoth’s long hair and resistance to cold, as well as creating imitation dodos from chicken eggs. A major step toward its beyond-elephantine goal, Colossal announced just last month that it had created elephant stem cells with the ability to be transformed into an embryonic state. The business announced in April that it would donate $7.5 million to universities conducting research on ancient DNA in 2024.
Shapiro recently discussed Colossal’s objectives and her new position at the company with Gizmodo. The transcript of our talk, slightly edited for clarity, is below.
Gizmodo: Things are happening so quickly. The dodo project wasn’t even publicized when we last spoke. Colossal CEO Ben Lamm recently stated that he believes it’s more likely that we’ll have a dodo before a mammoth, just because of the artificial womb issue. There was this open question of, well, how do you even go about de-extinction with birds?
Shapiro: It looks like a difficult technology to create an artificial womb. But that’s really awesome. I find it fascinating to be able to attempt to understand some really fundamental biology and to try to figure out the placental interface. To be honest, I never would have thought to work in that field. Upon closer inspection, I see that the team working on the artificial womb is made up of developmental biologists, engineers, and other individuals who are genuinely interested in solving this puzzle. It is astounding. That is, indeed, a considerable amount of time. Different species truly have different timings. There are various ecological, ethical, and technical difficulties connected to each species that is a candidate for de-extinction. As you say, there are different obstacles with birds if we’re only thinking about the technology to get us to a gene-edited embryo.
It is this method of editing primordial germ cells that Colossal and a few other academic research groups worldwide are employing. Primordial germ cells are those that, depending on the embryo’s biological sex, will eventually develop into either sperm or eggs. An embryo is around 24 hours old when a chicken egg is laid. You could not just edit it at that point. Both the number and variety of cells are excessive. It was simply not possible for you to do that. However, these early germ cells are moving outside the embryo in an attempt to settle in the gonads that are still developing at that time. After that, some of those primordial germ cells can be extracted from the egg using a needle without harming the developing embryo, and those can be injected into a lab dish. Such cells will survive under the correct culture conditions. You can also edit them. After that, you can reintroduce them into an embryo at the same developmental stage, at which point they will move externally and settle in the gonads. The DNA of that chick will be completely normal and unedited, but some of its gonads will be edited. If the objective is to use a lineage that doesn’t produce any gonads at all, then all of the gonads will be edited. Once edited eggs and sperm are fertilized with a chick, the result will be offspring with those edited DNA strands.
It will all become a little bit easier once we figure that out—which is a technological hurdle that we need to figure out, the right cultural conditions, how to get the edits in, et cetera—because you have eggs, fast generation times, multiple generations, and things like that. That is much simpler than the 22-month gestation period of an elephant, right?
Isaac Schultz, Gizmodo: You’ve been employed by Colossal for some time, and you’re leaving a few other significant gigs to work there full-time. When and why was the switch made?
Beth Shapiro: Since I’ve been working with them as an advisor in my capacity as the lead paleogeneticist, Ben has been attempting to convince me to join the team full-time. It has always been appealing. The possibility of creating instruments with a direct bearing on biodiversity conservation excites me much. Though the current state of affairs makes it extremely unlikely, it would be fantastic if one academic employee could make a significant contribution to this. assuming control of science at Colossal. It’s far beyond anything that an individual academic like me could have accomplished. I’ve watched the group grow and change, and every time I’ve been impressed. I went and saw all the things that they’re doing and thought, “Wow,” even though I had written the book that essentially said this was too difficult and would never happen. They will, in fact, arrive there. Furthermore, Ben has pledged to provide free access to these new tools and technologies for conservation as they advance. Which is excellent. Even though birds are among the most endangered species, we are unable to perform some basic DNA editing on their genomes, so any advancements we make in this area will be greatly appreciated. It would therefore greatly impact biodiversity conservation if we could make some fundamental discoveries.
Though it’s difficult to leave an academic role, I’ve been considering it for a while. Many people rely on you, and your lab is quite large. Furthermore, I wanted to guarantee that each member of my group at UC Santa Cruz had all they required to complete their training, be it a PhD, a current postdoc, or something else entirely. I was more concerned with making sure I was taking care of everyone in my lab at UC Santa Cruz than I was with precisely when I wanted to dive into Colossal.
Gizmodo: Since everyone seems to be fixated on de-extinction, I’d like to hear more about the time horizons of that phenomenon. When will all of this take place?
Shapiro: I’m really not in a position to comment on that either. I am attempting to locate everything. There is only one date that Colossal has actually made public, and that is 2028. Eriona [Hysolli], George [Church], and Ben are certain that they can have a mammoth by then. There’s a lot of science that needs to be discovered between now and then, and ideally we could forecast with precision when discoveries will be made, allowing us to build upon them. However, that isn’t how biology functions. Biology is filthy and difficult. It is not comparable to software.
Gizmodo: You stated that an elephant gives birth every 22 months. Would the gestation period still be 22 months in an artificial womb, or could it be accelerated?
Shapiro: I’m not sure. Currently, we don’t have a complete understanding of how to make an artificial placenta. We are not fully aware of all the complexities involved in the developmental process. We will discover all of this information as we go. Since a very large embryo is born during those 22 months, and because likely a lot of interesting biology occurs during that time, I would assume that we currently need the 22 months. To transform resources into an animal, a significant amount of time must pass. However, this is something we will discover.
Gizmodo: You once wrote the book arguing that de-extinction was not possible. You’ve also written about how this planet’s surface has changed due to human activity. How much has the de-extinction scene evolved since 2015, or even 2021, when you wrote those books?
Shapiro: Gene editing has advanced significantly in terms of accuracy, on-target gene editing, and simultaneous insertion of sizable DNA segments into a genome. We would require all of that stuff. A great deal of work has been done on ancient DNA. We now have a large number of additional mammoth genomes, which facilitates comparisons between the mammoth and elephant genomes. We can also ask where the similarities and differences between the mammoth and elephant genomes occur, which helps us determine what modifications are necessary. However, we still lack an artificial womb. We’re still investigating whether using elephants is necessary and, if so, how precisely we would employ animals in each of these processes. The core of all these technologies, though primarily developed for people or agricultural animals as model organisms, has, I believe, been developed now as science has advanced. While developing tools for genome editing, embryo transfer, and other related processes, the fundamentals of the technologies are all there; the question now is how to apply them to these species.
Gizmodo: There is an interesting dialogue taking place between the de-extinction projects and existing technology, which makes it feel a bit like—I don’t want to say chicken or the egg, just given that we’ve already kind of covered chicken and eggs. I believe that the goal of the de-extinction projects is to produce these new technologies so that they can be incorporated into the discourse on the other side.
Shapiro: I would personally love to see these technologies developed and applied to the conservation of species that are still alive, but I guess de-extinction is a moonshot. In order to truly solve these problems, we need to set a lofty objective and a moonshot to achieve in order to get there.
At [Geneva Science and Diplomacy Anticipation], I attended a meeting last week. We may go on and on about how much these technologies are needed, but we don’t really know where to begin. We were discussing all of the ecosystems that are in danger worldwide. Sayings like, “Okay, here is the list of technologies that we need to be working through, and this is a path to get there,” would arise if we simply had a moonshot—say, one ecosystem that we thought we could come together as an international community to save. De-extinction is what genetic rescue entails, too. We want to build a mammoth, according to a moonshot. So what do we need to create a mammoth? We need to make progress in the study of ancient DNA and loci that are chosen to modify the relationship between genotype and phenotype. We require improvements in the ability to genuinely alter DNA and alter it extensively. For elephants, we require advancements in cell culture. If we are to proceed in that direction, we must make progress in our understanding of how to genuinely have healthy and happy elephants in captive breeding settings. We must create a man-made womb. These are all technologies that can be used in the fields of genetic rescue and even human health. We have paved the way by claiming we will reach a mammoth and offering us this moonshot. We have established a moonshot that, in my opinion, compels us to advance these technologies in a way that we might not have otherwise.
Gizmodo: You mentioned that creating a route to reach a particular environment is possible. Giants working on a number of extinct animals. What is the reason for those species, and how can reintroducing them to their natural habitats help them recover?
Shapiro: The species have been chosen due to their diversity throughout the tree of life. We have a bird, a placental mammal, and a marsupial. The technological obstacles that must be overcome in order for us to develop a gene-edited embryo differ greatly between these three distinct species. Therefore, I believe that this gives us the opportunity to try to create technologies that will be useful to taxa all along the tree of life.
Regarding application to landscapes, once more, each species will face unique ecological challenges in this regard. For instance, in the case of the thylacine, we have an environment in which an apex predator went extinct not too long ago, and we know that this predator is still absent from that landscape, which is still sort of trying to rebalance itself following the extinction of this individual. There are many opportunities to work with scientists to better understand what might happen if we reintroduce an apex predator into that landscape, to develop the tools necessary to monitor changes to that landscape, to see what the local community and indigenous groups want from this landscape, and to work with them to develop strategies for releasing individuals into that landscape in the end.
Gizmodo: Developing a digital twin, or something similar, that would allow you to see precisely how the environment changes based on factors like the number of species in the habitat and other factors, would seem to be in the company’s best interest when it comes to ecosystem monitoring.
Shapiro: Modeling techniques that have been employed in the past don’t always involve creating digital twins. Ecosystems are intricate environments, and you can only truly comprehend the implications of a model’s failures to the extent that it is this sophisticated. There is a possibility that you will create a model that is so intricate that neither you nor the ecosystem will have learned anything when it breaks. Therefore, from a scientific standpoint, that is not very helpful. But it is unquestionably significant.
As a result, there is definitely interest in trying to predict ecosystem impacts way before the potential of actually having any ecosystem impacts. Colossal has been working on a paper to try and estimate the carrying capacity of mammoths—the carrying capacity of Arctic ecosystems for mammoths—thinking about things like, how much food would there be? How much space would you need? How many other species are there? What would the feedbacks be as far as the climate goes? Because moving these projects forward depends on carefully considering what would happen if we had animals that were actually released into the wild.
Gizmodo: This ecosystem is being created as part of the proxy mammoth project, which hasn’t existed in a long time. Colossal markets it as a way to lessen the effects of climate change. Is that the concept shared by all species?
Shapiro: Opinions among scientists regarding the possible influence on climate vary. I live in a different camp than George Church and Sergey Zimov, who genuinely believe that mammoths could aid in the permafrost’s cooling process. I don’t think there’s enough information available to confirm that. The precise number of mammoths required to support the ecosystem is unknown. As a company, I believe it’s critical that we consider every possible idea that exists before conducting the necessary research to ascertain the truth.
I do believe that the ecological effects will vary for each species, though. For instance, I don’t think that the presence of dodos in Mauritius will have a significant effect on climate change worldwide. Thus, I believe that provides an answer to your question: no, not all animals are meant to adapt to the changing global climate. The thylacine is intended to help create a more robust and resilient ecosystem in the face of climate change by reintroducing an apex predator into an ecosystem. For a mammoth and a dodo, the same is probably true. The most important thing about genetic rescue technologies, in my opinion, is that they can save species that are in danger of going extinct as well as de-extinction, or the creation of proxy species for extinct animals. Since it is well known that biodiverse, trophic-level redundant, and possessing redundant energy and food web systems are all characteristics of more resilient ecosystems. So these, in my opinion, are the goals that will be achieved by developing strategies and practical tools that will guarantee that we have a future that is both biodiverse and populated.
There is now an ecological result and an ecological example unique to each species. For dodo rewilding in Mauritius, for instance, the Mauritian Wildlife Foundation has teamed up with Colossal to identify potential habitats for dodo survival. Because dodos are flightless birds that lay a single egg in a ground nest, they went extinct. Additionally, after rats, cats, and pigs were introduced, the eggs on the ground were simply eaten by them. We are aware that the habitat that those specific invasive species require is necessary for the successful rewilding of dodos. Presently, the Mauritian Wildlife Foundation has an amazing history of carrying out practical conservation work in Mauritius. Currently, on an island known as Île aux Aigrettes, invasive species have been eradicated and even giant tortoises—another species that went extinct in Mauritius—have been reintroduced. They have also observed that many of the native plants began to flourish after the giant tortoises were reintroduced. They found that this was because the ebony seeds were being eaten by the tortoises, which put them in a better position to germinate through the tortoise’s digestive system. The restoration of these dodo-ready habitats will, in my opinion, result in unexpected interactions that we cannot have predicted. Additionally, other endemic species of Mauritius that are currently endangered will benefit immediately from the revitalized landscapes. The Mauritian Wildlife Foundation has increased its funding for some of the initiatives taking place in Mauritius simply because of the dodo’s existence.
Gizmodo: I must inquire about your dodo tattoo before we go past it.
Shapiro: It’s right here, resting on my arm.
Gizmodo: That’s right, nice. The illustration appears to be from the past.
Shapiro: My tattoo artist drew it from a book, yes. It serves as an example of science.
Gizmodo: Let us return to the technical aspects. Every species faces significant obstacles unique to itself. Which of these three species will take the longest to de-extinction to occur in terms of technological advancement?
Shapiro: All these technologies have a foundation. All that needs to be done is modify them to make them suitable for these species that people haven’t dealt with previously. Whether or not we want to make significant changes will likely be the largest obstacle, in my opinion. A significant amount of genome editing will be required if we are to resemble the extinct species as closely as possible. A few minor adjustments to restore these essential traits should be enough, in my opinion. It would be fantastic if we could restore the fundamental phenotypes with a few adjustments. “We’ve completed the de-extinction process,” I declare. However, there are purists among us. Working with Andrew Pask, who genuinely wants to implement every modification required to get a thylacine to 100% completion, is our way. And in order to do that, new instruments will be needed, such as those for creating artificial genomes from scratch or for splicing sizable segments of DNA into genomes. Those tools seem like they would have the longest timelines, in my opinion. To meet the objective of bringing these essential traits back from the targeted species, however, those aren’t really that important for Colossal.
Gizmodo: As you develop the technologies, how do you have these conversations and deal with the diversity of opinions within Colossal?
Shapiro: Our shared end goal is the same. Our goal is to advance these technologies to the point where we can de-extinction these three species, or at least as close to it as many of us are willing to accept it. However, we also wish to be able to use these technologies to conserve biodiversity because we are concerned about the planet’s future. And because it keeps us alert, I believe it’s beneficial to be able to discuss in detail how we’re going to get there and what the implications of this will be. It compels us to read on. We are forced to continue interacting with those who hold opinions that diverge from our own. It encourages us to continue these discussions in order to put ourselves in a position to learn more.
That’s the one aspect of this specific role that excites me the most. After working in academia for the past 25 years, I’ve been doing essentially the same thing, and now I’m trying a lot of new things. While I’ve given these issues some thought, I’ve never found myself in a situation where I had to fully comprehend them in order to be knowledgeable enough to make decisions or offer guidance to others as they proceeded. I adore it, too. I could jump right in and pick up a ton of new skills, which excites me so much. As a scientist, I feel renewed. And you feel as though the variety of viewpoints you come across sustains your motivation and excitement for your work because you can always prove me wrong and I’ll be proven wrong. Science ought to operate in this manner. Furthermore, it is boring if everyone is in agreement. Furthermore, it won’t lead us anywhere.
Gizmodo: Is there any chance that Colossal’s de-extinction agenda will include any additional species in the near future?
Shapiro: I believe we currently have a lot on our plates. However, one can never be sure. Not very soon.
Gizmodo: Is there anything else you would like to draw attention to?
