Bringing Extinct Species Back to Life | Dr. Beth Shapiro
In a Nutshell
Dr. Beth Shapiro leads Colossal Biosciences' efforts to de-extinct species like dire wolves, woolly mammoths, and dodos by making targeted genetic edits to their living relatives' genomes, using ancient DNA sequences to identify the specific traits that defined these extinct animals. The same synthetic biology tools developed for de-extinction—multiplex genome engineering, cellular rejuvenation, and iPS cell technologies—simultaneously advance conservation efforts for living species, including editing northern quolls to resist toxic cane toads and cloning black-footed ferrets to restore genetic diversity. The work operates within established regulatory frameworks and prioritizes animal welfare while addressing ecosystem restoration needs created by human-driven extinctions.
These notes were generated by AI and may contain inaccuracies.
Dr. Beth Shapiro's team at Colossal Biosciences has created direwolves through genetic engineering. They identified 20 specific genetic edits by sequencing genomes from fossil direwolves. These edits were selected because they encoded the traits that made direwolves bigger, more robust, and light-colored in coat compared to modern gray wolves. The team then engineered these specific changes into a gray wolf genome to recreate the direwolf.
The technology used for de-extinction is the same as what's needed for preventing living species from going extinct. The team is working on both goals simultaneously. The excitement generated by projects involving mammoths, dodos, and thylacines creates engagement, enthusiasm, and investment that funds the development of conservation technologies applicable to living species.
Dr. Beth Shapiro is an evolutionary biologist who previously served as a professor at UC Santa Cruz and an investigator with the Howard Hughes Medical Institute. She is now chief scientific officer at Colossal Biosciences, where her work focuses on de-extincting species including the woolly mammoth, dodo bird, and direwolf, while advancing broader species preservation through genomics.
Species is a human concept rather than a biological reality. Biology does not distinguish between species in the way humans do. The human tendency to categorize things into boxes enables communication, storytelling, and social structures.
The traditional taxonomy system was developed by Carl Linnaeus. The classification of American bison provides an example of how naming conventions developed. Europeans called large animals that could provide coats "buffalo" regardless of their actual biological relationships. This resulted in African buffalo, Asian buffalo, and American buffalo all sharing the same common name despite having no close relationship when examined through DNA analysis.
Taxonomists created the binomial nomenclature system to resolve naming confusion. American bison received the scientific name Bison bison, with plains bison designated Bison bison bison - the genus, species, and subspecies all being identical terms.
The biological species concept defines species based on the ability to breed and produce fertile offspring. This concept was developed by Ernst Mayr.
The genetic species concept classifies organisms based on thresholds of sequence similarity in their DNA.
The geographic species concept is used in conservation contexts, where animals living in different geographic locations may be classified as different species even if biologically similar.
Species concepts are tools for human communication rather than reflecting biological reality. Different contexts require different species concepts.
Dr. Shapiro's husband, Ed Green, worked with Svante Pääbo's group on assembling the Neanderthal genome. Research revealed that multiple lineages of human-like people existed simultaneously, including Neanderthals and Denisovans. The Denisovans were identified from a tiny finger bone found in Denisova Cave in Russia.
When anatomically modern humans moved out of Africa to colonize Europe, they encountered and interbred with Neanderthal populations. This violates the biological species concept if Neanderthals are considered a separate species.
Most people today carry between 2% and 5% Neanderthal DNA from this admixture event. The specific Neanderthal DNA segments vary between individuals - the 2-5% in one person's genome differs from the 2-5% in another person's genome.
The fossil record in Africa is fragmentary. Ancient DNA analysis provides advantages over traditional paleoanthropology because DNA from even small bone fragments can reveal whether that individual has living descendants or represents an evolutionary dead end.
Brown bears and polar bears diverged approximately 500,000 years ago. Despite this separation, they can interbreed when their habitats overlap, producing hybrid offspring called grolar bears or pizzly bears.
Ancient DNA analysis revealed that a polar bear from more than 100,000 years ago had brown bear ancestry that spread globally. During the last ice age, polar bears trapped on Alaska's ABC islands interbred with brown bears expanding from the mainland. All brown bears in North America today carry polar bear ancestry from this approximately 20,000-year-old interbreeding event.
Hybrid bears survive only as brown bears, not polar bears. Polar bear biologists hypothesize this occurs because brown bear ancestry prevents perfectly white fur needed for seal hunting success. The hybridization occurs only in one direction - brown bear males with polar bear females - due to differences in ovulation patterns and size differences between the species.
English bulldogs resulted from crossing bullmastiffs and pugs to create animals with short snouts for bull baiting. The breeding produced animals with large heads and small hips, requiring cesarean sections for birth because the birth canal cannot accommodate the head size.
When all Neanderthal DNA segments found across modern human genomes worldwide are combined, they represent more than 90% and possibly more than 95% of the original Neanderthal genome.
When all Neanderthal DNA segments found across modern human genomes worldwide are combined, they represent more than 90% and possibly more than 95% of the Neanderthal genome just from people who are alive today. This tells us that most of the Neanderthal genome was not maladaptive for people and that pretty much all of it could get passed on and live in healthy humans today.
We don't know what happened in the other direction. We see Neanderthal bones and there hasn't really been any evidence of humans admixing with Neanderthals. There has been evidence of hybrids between Neanderthals and Denisovans. This is really one of the most exciting things that ancient DNA has been able to contribute to understanding human disease and human medicine and what it means to be human. Before we had the Neanderthal genome, if we wanted to know what in our DNA makes us human, we would have to compare all the humans that are alive today with our closest living relative, which is a chimpanzee or a bonobo. So there's 3 to 5 million years of time between when we shared a common ancestor. And a lot of change happens in 3 to 5 million years in your DNA. And some of it is useful and some of it is what makes us human. And most of it is just not. It's just changed because of copying errors during copying cells and that's what happens. That's how we're different. Every child that's born has about a hundred differences compared to their parents because of copying error in the process of making the sperm and making the eggs that made that kid.
When we got the Neanderthal genome, that 3 million to 5 million year long branch leading to us was shortened to 300,000 to 500,000 years by an order of magnitude. So now if we want to know what it is that makes us human, we have a much smaller list of mutations or variants that we can look at. And because we now know that 95% of the Neanderthal genome exists in people today, we've narrowed that list down even further to that other 5%. What's going on in that 5% of the genome where no living person has Neanderthal DNA? That is where the stuff that the baby had to have the human version in order for that baby to survive. And that's where we look to see what it is that made us human.
If you just look at that 2 to 5% of Neanderthal DNA that we all have, most of it is not anything that is under selection. So you see it at about 3% frequency or so in different populations. What is interesting is when a piece of Neanderthal DNA is suddenly much more common in a population of humans because that would suggest that DNA from Neanderthal ancestry made the person more fit because they had that bit of Neanderthal DNA, were able to survive and have more kids than everybody else and so it increases in frequency compared to average. There are genes that are common in Latin American populations that come from Neanderthals that predispose to type 2 diabetes. There is another gene that was again in a Latin American population that makes people feel more or less pain, and it did have to do with pain sensation.
Most of the really interesting ones have been in immune related genes. During the pandemic, one of the first alleles that was discovered to be associated with negative risk or bad outcomes of COVID was a gene that came from Neanderthals. So it's a Neanderthal derived gene that was at something like 50% frequency, way above the 3% average frequency in Asian populations. And it made people more susceptible to the virus entering your lungs. And presumably it only became that high frequency because it was protective against some other disease that was circulating in the past. But the trade-off of that is that it made them more susceptible to COVID. There was another Neanderthal associated allele that was actually protective against COVID.
Our ancestors have been subjected to different diseases and pandemics and things that have happened throughout life and we see the traces of that in ancient DNA. We can now go into graveyards in Europe and actually isolate plague from dirt and from bones from people who died of plague and look and see how their immune systems and genes have responded to exposure to things like this.
This comes from studying MC1R, a gene that's associated with the red melanin. Mammoths as well had reddish colored hair based on evidence from their genome. There is some evidence from their genome that they had reddish colored hair.
All of the colors, if you look at African populations mostly, it's like dark eyes. I think that's probably the ancestral state, but there are lots of different eye colors that have evolved and I think they're selected for. People like things that are different and unique and so people want a mate that has blue eyes and stuff. Probably eye color was sexual selection. I don't know what other benefits blue eyes could have other than looking very stoic and cool.
People tend to think of their lives in the time bin of their lives, roughly 100 years if we're lucky. As somebody who studies long periods of time and what's happened to our species and other species across long periods of time, the question is how you pick the problems that you choose to work on. Why the woolly mammoth? Why not get the Florida Panthers rebooted completely? Maybe why not both? In terms of just where to focus, why bring back things from way back when as opposed to species that disappeared in the last 200 years? When you're making that decision, what's guiding it at the ethical level? What's guiding it at the practical level? What are you trying to accomplish?
There are technical, ethical, ecological, and social reasons to pick any of the species that you can. Technical: these are the easiest. We can't bring a dinosaur back to life because we don't have dinosaur DNA. The oldest DNA that we have ever recovered from a bone is from a mammoth bone. A mammoth's bone probably dates to around 1 to 2 million years ago. Dinosaurs went extinct more than 66 million years ago. That's far outside of where we're going to get recoverable DNA. And that's because the skeletons just don't - they're fossilized. They've turned into rock. There's no shred of DNA left.
As soon as an organism dies, the DNA in its cells starts getting chopped up into smaller and smaller fragments until eventually there's nothing left. This is really by three processes: UV light, which is why we wear sunscreen when we go outside, but the UV light hits your DNA and it actually breaks it. When we're alive, we have proofreading enzymes that will come and fix your DNA so you don't get cancer every time you go outside. But that is an energy requiring process. And after you die, there's no more energy. So the breaks from UV accumulate. Freezing and thawing is water molecules expand and will physically break the DNA fragment. So that's bad for DNA preservation. And most importantly, just microbial decay. The fungi, the bacteria that get into an organism when it's decaying and chew it up to transform that carbon and nitrogen into the next generation of organisms. And so that process is slower in some environments than others. Exactly in the same way that your sandwich will rot faster if you leave it in the sun versus in the shelf versus in the fridge versus in the freezer. DNA will preserve for longer in the cold Arctic where things are rapidly buried in frozen dirt and they stay that way for a million years, like this mammoth bone that we were able to recover DNA from. But if you die in a very hot, wet, swampy place like Mauritius, where the dodo lived, it's another one of the species that we're working on at Colossal. Very little chance you're going to be able to recover DNA from any of the fragments that are on Mauritius Island. And I have tried like hundreds of bones from Mauritius. We have a great dodo genome, but it's from a bird that went to Europe alive on a ship and is part of the collection at the Danish Museum of Natural History. So you have to have a well-preserved sample that you can get DNA from. Ideally many of them because you want to know what are the DNA changes that made a mammoth a mammoth instead of another type of elephant. Many of them will help you to do that. But one is good enough to get some sort of template for what you're going to do. You probably should know what caused that species to go extinct in the first place so that you don't bring something back that becomes the first species to be de-extinct and then the first species to be re-extinct or bring back something really nasty that knocks out a bunch of other species.
You have to understand the role that that animal played in the ecosystem and whether that niche is still available. Ecosystems don't live in a vacuum just waiting for something to come back. And in some cases, there's a real ecological driver for the species that we're focusing on. We feel like there is a real ecological role for these species to play. That these ecosystems are destabilized because of extinction. And by bringing back these key ecological interactions, we can make those ecosystems more robust and more resilient in the face of all the crap that people are always throwing at our natural ecosystems.
If you think about what large animals, large herbivores do in their ecosystem. They turn the soil by walking around. They knock down things. Elephants knock down trees. Mammoths probably lived places above trees, so that wasn't what they were doing, but they were distributing seeds and nutrients. Pleistocene Park is up in northeastern Siberia. There are these two scientists, Sergey Zimov who's a Russian Academy scientist and his son Nikita. They've been running this park up in northeastern Siberia for a long time. And they have been really interested in understanding what happens when you restore all of the species that used to live on the tundra to the tundra ecosystem. And they have bison that they've brought in from Canada and wild horses and several species of deer and muskox. And they've seen that having the animals on the landscape that they've fenced off actually causes the plants to come back with more veracity. So these animals, they have to eat during the winter. So in order to find food, they scrape the snow off of the surface of the dirt. In the absence of these animals, the snow stays on the surface and snow is a very efficient insulator. So, it traps the summer heat in that frozen sediment, causes the sediment to melt faster, and when the plants come back, it's a particular type of plant that can live in that moist sediment. With the animals, you get a mosaic landscape where there's some parts that are moist and wet. There are other parts that have been exposed and they're dry and colder and you get broader diversity of plants that are coming back where these animals are. So, they are essentially recreating their ecosystem just by being there.
When I joined Colossal, we didn't have a bird program, but I really wanted there to be a bird de-extinction program because all of the tools that we are developing for de-extinction are the same tools that we can use to use synthetic biology to modify the genomes of living species and help them avoid becoming extinct. And so the kit that we're building from multiplex genome engineering to cellular rejuvenation to iPS cell technologies for wild animals to even learning the link between particular letters of the DNA sequence and what those letters actually do to cause an animal to look the way that it does. All of that is applicable across the board. So the stack that we're building for de-extinction for synthetic biology stack applies to synthetic biology for conservation. So when I joined Colossal and there wasn't a bird program, they had launched the mammoth program which is a placental mammal and the thylacine program or Tasmanian tiger that's a marsupial mammal. But birds are among the most endangered species on the planet and it is not possible to clone birds using somatic cell nuclear transfer, the process that most famously brought us Dolly the sheep because we don't have access to the egg cells at the right stage. So while that process is really pivotal and integral to our mammoth and thylacine and the other mammalian project, it's just not possible to use it for birds. And so I wanted a program that was going to help us develop technologies for birds. So why did we pick the dodo compared to any other bird for the first one?
Cool beak. It comes down to that which I also think is a really important part of talking about this project and it's the idea of awe of being excited about something. We get kids drawing animals that drawing mammoths and thylacines and dodos and sending them to us all the time. Ben has put them in frames up around some of them are good. The dodo with its sort of rounded top beak also and the way the eyes are typically drawn. It also has a kind of cartoonish friendly toucan Sam type of look. Well, it was in Alice in Wonderland. Most of what we know about the dodo is from cartoonish drawings of this animal. There are some and of course there's skeletons that we can piece together using the many many bones in Mauritius that do not have any DNA in them based on my very best tries.
A few years ago, there was something where one female condor just having an egg all on her own. My scientific explanation is that meiosis didn't fully separate and she ended up having a fertilized egg. So the separating of the cells during the very early phase when you're making eggs or making sperm, you're trying to duplicate your cell, but instead of that, you make two versions of the cell that only have one copy each of your chromosomes. So when normally in normal reproduction, an egg that has one copy of the set of chromosomes and a sperm that has one copy of the set of chromosomes come together, they're fertilized. The resulting eventually embryo has two copies, one from mom and one from dad. In this case, there was no sperm. There was an egg that had both copies, probably because of a mistake during meiosis. Like, they didn't separate out properly and that was able to develop full term. The offspring was viable.
In humans where that happens and it does happen on certain chromosomes these homozygosity effects they happen under certain conditions like there are these paternal or maternal imprinted conditions like Prader-Willi syndrome where paternal DNA gets kicked off and you have two copies from mom which doesn't sound like a bad thing unless there are things on the paternal chromosome that are required for development and the reverse also happens like in Angelman syndrome I think it is that all the genes that everyone healthy walking around out you and me and have genes that only came from our mom and only from dad. And so if you get two copies from mom of a chromosome or two copies from dad, you end up with pretty severe deficits in brain development and other things. And some things. And you also could never be a boy because the one gene that turns on that cascade of male development is called SRY. It's on the Y chromosome. So without that gene, you would never be a boy. You would always be a girl. Trisomies where you get two copies from mom and one copy from dad. Those can also be bad because of different levels of gene expression. Down syndrome is trisomy 21 and there are a few other trisomies that are compatible with life. Trisomy 21 is the most common one because those people can live obviously with some challenges additional challenges because the additional chromosome but they can live full lives till relatively middle age.
Sex has evolved a bunch of different times on the animal or the tree of life. And so different ways of doing sex have evolved. So we have this XY process where the males are what we call the heterogametic sex. So the males have an X and a Y and the females have two X's and they don't have a Y. But birds do it differently. They have the WZ and it's the females that have the two different chromosomes. The males that don't. And then there are alligators and crocodiles and they do sex determination based on the temperature at which the egg is sitting during a very critical period during development. There are communities online that believe this kind of stuff for humans. There are all these theories about how to get a male or female offspring based on position of intercourse, temperature, location, food. None of it beats chance. Or if you really want it, the process by which you take an egg and you take a particular sperm that you know whether it's carrying the Y chromosome or not and use that to fertilize. You can actually determine the XX or XY of the sperm and they can do that now. You can select so you can do true sexual selection. You can and it's because the Y chromosome is teeny teeny tiny compared to the X and so you can centrifuge them and because they're smaller they sort out.
Different methods can be used to determine the sex of cloned animals. One approach involves using sperm or eggs with different weights that spin out to different depths, allowing researchers to bias the likelihood of getting a male or female. Another method used at Colossal involves cloning from somatic cells, where the sex is already known because the process starts with a tissue cell from the animal rather than using sperm and egg.
Meiosis produces sperm or eggs with half the chromosomes, so that when conception occurs the chromosomes combine to create an embryo. In mammals like the woolly mammoth, this process is straightforward. However, birds present significant complications in reproductive biology. Some birds have a germline restricted chromosome that exists only in sperm and eggs and then disappears from other cells. Birds also have microchromosomes that are difficult to assemble during genome sequencing.
Mammoths are identified as mammals through genome sequencing rather than just physical characteristics like fur. High-quality whole genome sequences have been obtained from multiple mammoths dating back 1.5 million years. These sequences can be assembled using computers and compared to living animals. The closest living relative to mammoths is the Asian elephant, and mammoths are actually more closely related to Asian elephants than Asian elephants are to African elephants.
Complete genomes are represented in most cells, though not all genes are expressed in every cell type. The epigenome determines which genes are expressed, creating differences between hair cells, skin cells, and heart cells, but the complete genetic menu remains present in each cell.
The approach used in Jurassic Park, extracting dinosaur DNA from mosquitoes preserved in amber and filling gaps with frog DNA, is not how modern de-extinction works. Instead, researchers use the close genetic relationship between mammoths and Asian elephants. Genome sequencing shows that mammoths and Asian elephants are approximately 99% similar, which is comparable to the genetic similarity between humans and chimpanzees.
The goal is not to recreate identical copies of extinct animals but to engineer animals capable of filling ecological niches. The genetic species concept, which classifies organisms based on sequence similarity thresholds, was designed for organisms evolving through natural bifurcating phylogenetic processes over long time periods. This concept does not apply to de-extinction or synthetic biology, where animals are engineered to solve specific problems.
Rather than trying to recreate any particular individual mammoth, the focus is on identifying genetic sequences where all mammoths are the same as each other but different from elephants. These sequences represent the traits that make mammoths distinct. The resulting animals must be capable of living in today's habitats, including surviving with current pathogens, microbes, food sources, and microbiomes that elephants can survive in.
The dire wolf project involved making 20 specific genetic edits to grey wolf genomes based on sequences from fossil dire wolves. These edits were selected to recreate traits like larger size, more robust build, and light-colored coats. The animals created have 20 specific genetic modifications that distinguish them from grey wolves.
The dire wolves are larger than grey wolves on average at the same age. They are more muscular with longer, fuller, light-colored fur. The selection of genetic edits was deliberate, focusing on traits that could eventually allow the animals to be released while ensuring safety and health.
When engineering the light-colored coat trait, researchers found that the same genetic variants present in dire wolves could cause oculocutaneous albinism (blindness or deafness) in grey wolves. Instead, they used different genetic edits that are known to be safe because they exist in living dogs with light-colored coats. This approach prioritizes animal welfare and safety while achieving the desired trait.
Creating woolly mammoths from Asian elephants requires changing not just hair structure but also skin itself, including increasing follicle density and sebaceous glands to support a woolly coat. These changes must result in healthy animals, which is particularly important given that elephants have 22-month gestation periods and reach sexual maturity at 14 years.
Three dire wolves currently exist: Romulus and Remus are males approximately two years old, while Khaleesi is a female about 18 months old. The animals are too closely related to breed, so hormone treatments are used to prevent reproduction. They were hand-reared and live together, though they display wild animal behaviors rather than domestic dog behaviors.
The dire wolves are wild animals, not domestic dogs. At approximately 120 pounds, they are larger than typical grey wolves. They exhibit different individual personalities, with some being more skittish around humans than others. The animals require professional handlers and are not safe for untrained individuals to interact with.
Additional dire wolf packs will be created to allow better study of ecosystem impacts. The priority is currently on other species rather than expanding the dire wolf population. The animals are being studied to understand gene effects on lifespan and habitat interactions before any potential release.
De-extinction projects operate within existing regulatory frameworks rather than as independent operations. Any release of animals requires compliance with multiple agencies. The first gene-edited organism created specifically for conservation and ecosystem restoration, an American chestnut tree, was recently deregulated by the USDA.
The American chestnut was the most prolific tree across eastern North American forests until the early 20th century, when a fungus introduced through Chinese chestnut imports killed approximately a billion trees over a decade. The gene-edited American chestnut represents the first genetically modified organism approved specifically for ecosystem restoration purposes.
Humans have been influencing evolution and ecosystems throughout their existence, initially through driving species extinct through hunting, then through domestication, and now through conservation efforts. Conservation involves active management decisions about population sizes, feeding, vaccination, and predator protection. The notion that conservation means leaving ecosystems completely alone is not accurate.
Ecosystems with multiple species performing different functions have greater biodiversity and richer environments. Overlap in ecological niches creates redundancy that helps ecosystems weather disturbances. The assumption that only currently existing ecosystems are optimal may limit thinking about ecosystem management and restoration approaches.
Scientists working on de-extinction projects operate within established regulatory environments rather than as independent actors. The work involves collaboration with existing institutions and follows legal frameworks in the locations where animals would be reintroduced. This stands in contrast to fictional depictions of unregulated scientific experiments.
Public perception challenges stem from a psychological tendency to romanticize the past. A book titled "The Good Old Days They Were Terrible" illustrates how historical periods often included serious problems like dysentery and lack of antibiotics, yet people tend to focus only on positive aspects. Additionally, humans lack a window into future outcomes, making it difficult to evaluate the potential impacts of reintroducing extinct species.
Native American populations historically transported fox species to islands including Anacapa Island and Santa Rosa Island using boats. These introductions created biodiversity that is now protected, demonstrating that human-mediated species movement can result in valued ecological outcomes. The perception of these introductions as acceptable appears linked to their historical timing and cultural context.
Restoring top predators can create cascading ecosystem benefits, as demonstrated by the gray wolf reintroduction in Yellowstone National Park. The wolves reduced overpopulated prey species that had consumed excessive shrubbery. This led to plant regrowth along river edges, which changed river flow patterns throughout the ecosystem.
The thylacine, also known as the Tasmanian tiger, represents the second de-extinction target for Colossal. Tasmania currently experiences problems due to the absence of this top predator. The Tasmanian devil facial tumor disease affects the population because sick individuals are not naturally weeded out without top predators present. The disease spreads between individuals due to their close genetic similarity.
De-extinction work serves dual purposes: restoring extinct species while developing tools to prevent living species from becoming extinct. The same technologies, tools, and scientific approaches apply to both objectives. Public engagement with charismatic extinct species like mammoths, dodos, and thylacines generates investment and enthusiasm that supports broader conservation technology development.
The northern quoll faces extinction risk in Australia due to introduced cane toads, which are toxic to the marsupials. A single letter change in one gene enables some mammals to consume cane toads without dying. Colossal Australia partners have successfully made this genetic modification in northern quolls. Laboratory testing demonstrated that this single nucleotide change allows the toxin to break down, potentially preventing quoll extinction while enabling them to eat the invasive cane toads.
Public distrust of scientists increased following the pandemic, with some viewing scientists as self-interested rather than focused on societal benefit. This perception exists despite institutional review boards and other constraints designed to ensure ethical conduct. Similar concerns appear in discussions about artificial intelligence development.
Mosquito control presents complex ecosystem considerations. Not all mosquito species carry diseases like malaria and dengue. Disease-carrying species often have higher population densities due to human-created water sources like standing water in containers. Arctic regions demonstrate naturally high mosquito populations without human presence.
Rather than eradicating mosquito populations entirely, gene editing could prevent disease transmission while preserving ecological roles. Gene drives represent one approach, though they require safety measures including built-in limitations on generational persistence. Natural selection typically works against gene drives since mutations that break the drive and restore reproduction are favored.
Cheat grass, an invasive Mediterranean species, creates significant fire risks across western North America due to its shallow root system and high flammability when dry. Native California grasses have deeper roots, remain green longer, and sequester carbon more effectively. Gene drives could potentially reduce cheat grass populations enough to allow native grass recovery and reduce fire risks.
The 1990s translocation of Texas panthers into Florida successfully addressed inbreeding depression in the Florida panther population. The isolated Florida population had developed problems including crooked tails, cowlicks, and cryptorchidism. Introduction of Texas panthers resolved these genetic issues, though the population faces renewed inbreeding risks due to continued isolation from Texas populations.
Ecosystem modification decisions require weighing the risks of technological intervention against the risks of inaction. Habitats worldwide suffer from human-caused changes, with species facing extinction rates too rapid for natural selection to address. Choosing not to use available technologies like translocation, assisted reproduction, genetic modification, synthetic biology, and de-extinction represents acceptance of reduced future biodiversity.
De-extinction projects employ advisory panels including local stakeholders. The Tasmanian advisory panel includes politicians, forest industry representatives, animal workers, scientists, and conservation biologists. The moa project is led by the Nitahu Research Center in New Zealand's South Island, with Maori people serving as long-term stewards who make decisions about population numbers, specific animals, release locations, and methods.
Open communication about de-extinction work generates both positive and negative responses but increases public engagement with synthetic biology concepts. The dire wolf announcement prompted discussions across university ecology, sociology, and anthropology classes, with students feeling increased agency regarding their environmental inheritance. Middle school and high school students also expressed excitement about the possibilities.
In vitro fertilization enables genetic selection of embryos based on health criteria. A case in China involved gene editing of babies to disrupt the HIV receptor, with questions about whether the modification was intended for disease prevention or potential cognitive enhancement. The researcher faced legal consequences from Chinese authorities.
Multiple companies now offer deep sequencing of embryos for both IVF and non-IVF babies, providing information about disease risks as well as traits like predicted height and intelligence. This raises ethical questions about genetic selection in humans, though mate selection already involves choosing partners based on physical, emotional, resource-related, and cognitive characteristics.
Initial public responses to new technologies often involve fear assessment before curiosity can develop. This pattern appears consistent across different technological developments, including genetic selection applications.
Height is a relatively easy trait to study because it is heritable and visible, unlike IQ which is difficult to pin down across cultures. Ancient human DNA analysis shows that genes for tall stature were introduced into Europe around 4,700 years ago by the Yam Nia steppe people. While environmental factors like improved health and nutrition contributed to increased height in Northern Europe, the Dutch population has now reached what appears to be the maximum height possible with current genetic variants. This demonstrates human genetic selection for a visible trait without any artificial embryo selection process.
The discomfort people feel about genetic engineering stems from the idea that one generation might remove freedom of choice from the next generation. While humans readily accept engineered traits in dogs like Chihuahuas and boxers because we created their social roles, the concept of humans having predetermined niches feels fundamentally different.
Baby KJ became the first child cured of a genetic disease using synthetic biology tools. Born with urea cycle deficiency causing dangerous ammonia buildup in the blood, he received a bespoke CRISPR base editor designed through collaboration between academic researchers, industry, NIH, and Children's Hospital of Philadelphia. The treatment involved six months of development, safety testing, and three administrations of the CRISPR medicine as a six-month-old, resulting in a complete cure.
This case illustrates that humans have been exerting influence over other species for millennia. From domesticating grey wolves into dogs 30,000 years ago to transforming teosinte into corn, every decision about which species to protect or modify represents human intervention in natural systems. The modern world is fundamentally a human-shaped environment, and species that thrive today are those that have adapted to human-created niches.
Black-footed ferrets faced near-extinction when prairie dog populations were deliberately reduced by farmers, inadvertently killing the ferrets that depend on prairie dogs as prey. After the species was declared extinct, a family dog named Shep in Wyoming killed what proved to be a surviving black-footed ferret, leading to the discovery of a remnant population near Meeteetse, Wyoming. Scientists collected individuals from this population for captive breeding programs.
One individual named Scarface became a prolific breeder, siring over 300 litters. However, this created a genetic bottleneck since all founders originated from the same Wyoming population. The San Diego Frozen Zoo preserved tissue samples from the original captive breeding population, representing genetic diversity unrelated to the Meeteetse animals.
Scientists successfully cloned Elizabeth Anne in 2020 from 40-year-old tissue samples using somatic cell nuclear transfer, where an egg cell receives the nucleus from a preserved skin cell. While Elizabeth Anne proved non-reproductive, a second clone from the same genetic line successfully reproduced, providing offspring that could be introduced into the wild population.
This approach demonstrates how cloning can simultaneously serve as a genetic rescue tool while addressing diversity loss. The collaboration between US Fish and Wildlife, San Diego Frozen Zoo, and Revive and Restore shows how multiple conservation tools can be deployed together.
Plague remains the primary threat to wild black-footed ferrets. Since domesticated ferrets show genetic resistance to plague, researchers are working to identify the specific genetic variants responsible. Once identified, synthetic biology and gene editing could be used to introduce plague resistance into black-footed ferrets, allowing them to survive in habitats altered by human activity.
The dodo project includes work with the Mauritius pink pigeon, another island species requiring conservation intervention.
Dire wolf DNA proved difficult to sequence due to poor preservation in warmer climates where the animals lived. The research began before involvement with Colossal Biosciences, with initial publication attempts timed to coincide with Game of Thrones release for publicity, though the DNA quality prevented completion in time.
AI and machine learning could enable creation of digital twins of ecosystems, allowing researchers to model perturbations and predict outcomes across multiple interacting species and environmental factors. This approach surpasses human cognitive limitations in processing complex ecological interactions.
Care reports provide comprehensive ecosystem impact assessments for any future de-extinct animal releases, incorporating input from local stakeholders, conservation biologists, and multiple perspectives to evaluate short, medium, and long-term consequences.
Within 3-5 years, gene editing technologies like HIV receptor modification are predicted to become commonplace in fertility contexts. When genetic variants definitively predict disease, the ethical imperative to prevent suffering may override current hesitations about human genetic modification.
Public acceptance of new technologies often depends more on delivery methods than the underlying science itself. Just as GLP-1 drugs reduced needle phobia through convenient pen delivery systems, and smartphones made computers approachable, non-invasive brain-machine interfaces could eliminate fears associated with current implantation methods.
The book "Life as We Made It" explores humanity's long history of species modification and considers scenarios where crisis situations might push society toward accepting human genetic editing as an ethical necessity.
An artificial womb is being developed specifically for mammoths rather than relying on Asian elephants to carry mammoth pregnancies for 22 months. The goal is to birth multiple mammoths simultaneously without using elephants, allowing elephants to make elephants. This technology development also creates opportunities to help people and other species. One example involves a friend diagnosed with breast cancer during pregnancy who had to choose between delaying therapy until birth or risking the baby. An artificial womb could allow the baby to develop outside the mother, enabling earlier treatment. Another application involves babies needing surgery that cannot be performed in utero, providing a safe way to have the baby come out.
Current NICU (neonatal intensive care unit) technology represents a form of artificial womb technology already in use for pre-term babies. The technology is far from perfect but has come a long way. A more sophisticated NICU will be possible through understanding how genes map to phenotypes, using genetic resources from all people, learning about epigenetics, and building technology that builds on developmental process understanding.
Public reaction to revolutionary education approaches, such as AI tutors combined with hands-on learning like farming and business, tends to be divided between those who see the potential and those concerned about cost and accessibility for rich kids versus everyone else. Scholarship programs are being implemented to address equity concerns. The goal is to figure out the best way to educate humans and then scale it to everybody. Pioneering work always stimulates concern about the "haves and have nots." Being a pioneer is hard because people assume work is financially driven or question why resources aren't focused on species needing help right now.
Scientists working on de-extinction face criticism that they should be curing cancer or saving living species instead. The response is that both activities are happening simultaneously. There is not enough money in conservation, and de-extinction tools are immediately applicable to existing conservation problems. New funding, resources, investment ideas, excitement, enthusiasm, and student engagement are being brought to conservation through this work. The direwolf announcement included the cloning of red wolves, the most endangered wolf species in North America, endemic to a very small population with captive breeding in the Carolinas. A population of coyote-like animals with more than 75% red wolf ancestry was discovered, and these wolves were cloned to introduce new genetic diversity into the existing red wolf population using the same toolkit developed for direwolves.
Scientists and technologists need to be really drawn to or obsessed with their projects because the person doing the work matters. Some scientists work on pedestrian stuff, while others want to be on the cutting edge. Without obsession with the question, nothing gets accomplished. This is similar to how Elon Musk is obsessed with going to Mars and cannot be drawn off target. People should accept this about individuals who move things forward. Howard Hughes liked aircraft, and you cannot convince people to work on coral reefs if their obsession is elsewhere. People shouldn't feel bad about not being able to do everything, as trying to do 10 things instead of one results in getting way less done and making less impact.
Colossal has about 120 scientists plus other people involved. A huge social media team puts science bits out targeting different audiences with different types of information. They work with podcasters, documentary teams, and film teams. Papers are published through traditional peer review processes, and some papers are posted on archives when faster information dissemination is needed before peer review. Multiple communication methods are being used. National Geographic explorer status enables participation in National Geographic live series, talking to communities about conservation, genetic rescue, de-extinction, and a future that can be both biodiverse and filled with people.
Beth Shapiro attended the University of Georgia as a broadcast journalism major and worked for the local TV station in Northwest Georgia, doing local cut-ins on Headline News. She was news director of a local radio station while a freshman, requiring her to be at work at 4:00 AM for drive time shows. After her freshman year, she took an honors program class in geology and archaeology that traveled from the east coast across the country, sleeping in national parks, learning about minerals, coastal dynamics, national park formation, and landscape formation. The class also visited archaeological and anthropological sites. This experience led her to want to be a science journalist. She started taking science classes and went to Panama to study parasitoid wasps on Barro Colorado Island, focusing on ecology and population ecology rather than genetics or evolution.
While in Panama, Shapiro met someone starting a lab in Edinburgh and developed a proposal to study wasps that switch between inbreeding and outbreeding, questioning whether the switch to inbreeding purges deleterious alleles from the genome. She applied for scholarships to go to Edinburgh but did not get a first-round interview for the Marshall Scholarship. She received a Rhodes Scholarship instead and went to Oxford. At Oxford, she met Alan Cooper, a Kiwi setting up an ancient DNA lab, one of the few labs built to process old samples. She was excited about ancient DNA because it combined geology, paleontology, and storytelling, allowing DNA sequences from entire ecosystems to tell stories about environmental changes when people first arrived or with rapid warming out of the last ice age.
Shapiro got into de-extinction because everyone working in ancient DNA is asked about bringing dinosaurs back to life whenever they publish papers. This question persisted even after the first ancient DNA publication in 1984, when researchers from Berkeley isolated a tiny DNA fragment from a preserved quagga (an extinct zebra type) using molecular cloning, proving DNA survived after death. When journalists interviewed Alan Wilson, the first ancient DNA researcher, they asked the dinosaur question first. People tend to settle on mammoths or saber-tooth cats after learning dinosaurs cannot be brought back due to lack of DNA. Mammoths are popular because they're big, relatively recent, ancestors hunted them, we can imagine what they looked like, and they're in popular culture.
The work involves repairing ecosystems and making better ecosystems. Progress is supported, including walking away from a thriving academic lab and Howard Hughes Investigator position to pursue this mission with anticipation of positive outcomes for animals and people.
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