De-Extinction & Conservation: A New Era

Researchers at Colossal Biosciences are utilizing ancient DNA to identify specific genetic traits of extinct species, such as dire wolves, to engineer these characteristics into living relatives.

For dire wolves, 20 specific edits were selected from fossil genomes to impart traits like increased size, robustness, and light-colored coats, which were then introduced into a gray wolf genome.

This dual approach not only aims to resurrect extinct species but also applies the same genetic tools and technologies to prevent currently living species from facing extinction.

Public fascination with iconic extinct animals, including mammoths, dodos, and thylacines, plays a crucial role in generating enthusiasm, engagement, and investment necessary for developing these advanced conservation technologies.

The traditional 'biological species concept,' introduced by Ernst Mayr, defines a species by the ability of organisms to interbreed and produce fertile offspring, serving as a foundational yet limited framework.

In contrast, the 'genetic species concept' classifies organisms based on a predefined threshold of genetic sequence similarity, offering a different lens for taxonomic categorization.

Conservation efforts often employ a 'geographic species concept,' which distinguishes populations based on their spatial distribution, as seen in the classification of Florida and Texas panthers.

Ultimately, no single species concept is universally applicable; the choice of concept depends on the specific scientific inquiry or conservation objective at hand.

Evolutionary divergence is primarily driven by the accumulation of random mutations within populations that are geographically or reproductively isolated from each other.

Small population sizes significantly increase the likelihood that even disadvantageous mutations can become fixed within the gene pool purely by chance.

When two lineages re-establish contact after a period of isolation, their ability to interbreed successfully depends on whether the accumulated evolutionary changes have led to reproductive barriers, such as issues with sperm-egg fertilization.

For instance, humans and Neanderthals diverged approximately 300,000 to 500,000 years ago, a relatively short evolutionary period, yet interbred, akin to brown bears and polar bears, which diverged half a million years ago and still readily hybridize in overlapping habitats.

Modern humans typically carry between 2% and 5% Neanderthal DNA, but the specific segments of this ancient DNA vary considerably among individuals.

When combined, the diverse Neanderthal DNA segments found across modern human populations can reconstruct over 90% of the entire Neanderthal genome.

Neanderthal DNA persists in the modern human gene pool, reflecting that most of these inherited genetic contributions were not maladaptive.

Regions of the human genome where Neanderthal DNA is consistently absent often highlight genes crucial for human survival, providing insights into what genetically defines humanity.

The MC1R gene, known to be associated with red melanin pigmentation, has been identified in both Neanderthal and woolly mammoth genomes.

Physical evidence from preserved mammoth mummies corroborates genetic findings, confirming the presence of reddish hair coloration in these extinct proboscideans.

A shared biological mechanism for red pigmentation links diverse species that have evolved along similar evolutionary paths or within cold climates.

Despite extensive efforts, retrieving viable dodo DNA from numerous bones found on Mauritius has been largely unsuccessful due to poor preservation conditions in a hot, wet, and swampy environment.

The successful mapping of the dodo genome was ultimately achieved using a single, exceptionally well-preserved specimen from a European museum collection, transported alive from Mauritius to Europe centuries ago.

Ideal genetic template creation for de-extinction requires multiple well-preserved samples to accurately identify the unique genetic changes that distinguish an extinct species from its living relatives.

Understanding the original cause of extinction is critical to prevent re-extinction, and the chosen species should have an ecological role that can still be filled in current ecosystems to enhance resilience.

Mammals, including humans, typically determine sex through the XY chromosome system, where males are heterogametic (XY) and females are homogametic (XX).

Birds, in contrast, utilize a WZ system, where females are heterogametic (WZ) and males are homogametic (ZZ).

Reptiles such as alligators and crocodiles exhibit temperature-dependent sex determination, where the incubation temperature of eggs dictates the sex of the offspring during a critical developmental period.

Despite various cultural theories, there is no scientific evidence to support human control over offspring sex through environmental factors like intercourse position or diet; current methods involve direct genetic selection in assisted reproductive technologies.

Genetic engineering relies on the 99% genome overlap between woolly mammoths and their closest living relative, the Asian elephant, to target the specific 1% of genes responsible for cold-climate survival.

This high degree of genomic similarity allows researchers to focus on identifying and editing the critical 1% of genetic differences that conferred mammoths their unique traits and environmental adaptations.

The goal is not to create an exact clone of an individual mammoth but to engineer an elephant capable of thriving in the cold, permafrost environments mammoths once inhabited.

The engineered mammoths will need to be genetically equipped to survive with modern pathogens, microbes, and food sources, compatible with the biological systems of their elephant surrogates.

The recreation of the dire wolf involved introducing 20 specific genetic edits into a gray wolf genome, selected to manifest traits like increased size, robustness, and a light-colored coat.

Prioritizing animal welfare, the genetic engineering process meticulously avoids introducing variants that could lead to health issues; for example, specific light-coat genes linked to oculocutaneous albinism (blindness or deafness) in dogs were deliberately bypassed.

Instead, alternative, safe genetic pathways for light coat color, already present in living domestic dogs and gray wolves, were utilized to achieve the desired dire wolf aesthetic without compromising health.

Currently, two male dire wolves, Romulus and Remus, and one female, Klesia, are alive, and while they are not intended for mating due to close relatedness, the team continues to study these animals to learn about their genetics and behavior.

Ellen Carlson of the Broad Institute found that mapping specific genes to complex behavioral traits remains a significant challenge. Ellen Carlson has shown that breed stereotypes are not real.

Historical trends show that different dog breeds have been demonized in the United States, starting with German Shepherds post World War II, followed by Dobermans, Bulldogs, and currently Pitbulls.

The ability to map specific genes to complex behaviors remains elusive for most dog breeds, with the exception of the Chihuahua.

Breed-based generalizations currently lack a firm basis in genetic evidence.

Conservation should not be viewed as merely leaving nature untouched but rather as the active management of populations and environments, according to Dr. Beth Shapiro.

Humans have continuously influenced ecosystems through activities such as hunting, domestication, and the global relocation of species for tens of thousands of years.

Shapiro advocates for prioritizing ecological 'robustness' and resilience over attempts to preserve a specific historical state of nature, acknowledging the constant flux of ecosystems.

She notes that if an ecosystem has multiple species performing diverse functions, it leads to greater biodiversity and richer environments, making them more resilient to adverse events.

Initial proposals to eradicate disease-carrying mosquitoes faced opposition from biologists because they provide a food source for birds, illustrating how removing a species can trigger a domino effect of ecological consequences.

Targeting only specific mosquito species that transmit diseases like malaria or dengue is presented as a more viable strategy than total eradication, given the ecological importance of other species.

The high population density of certain disease-carrying mosquitoes is attributed by Dr. Shapiro to human urban development, which creates conducive breeding grounds compared to natural environments.

This technology could be deployed to control flammable invasive species, such as cheat grass, which is Mediterranean in origin and contributes to wildfires across Western North America, to help restore native California ecosystems.

Safety measures for gene drives include engineering 'switches' that limit their activity to a fixed number of generations, preventing unintended long-term ecological impacts.

The use of such tools could restore the robustness and resilience of ecosystems damaged by invasive species or other human-induced changes, as seen with the reintroduction of Texas panthers to bolster Florida panther populations in the mid-1990s.

While environment plays a role, Northern European height has plateaued, suggesting a biological limit reached with the genetic sets introduced by Yamnaya steppe people 4,700 years ago.

Ancient human DNA studies reveal that genes contributing to tall stature were introduced into Europe approximately 4,700 years ago by the Yamnaya steppe people.

Environmental factors influence height, yet the observed plateau in Northern Europe implies that a biological limit exists within the current range of genetic variation.

Dr. Beth Shapiro argues that using available tools to improve global health and well-being is a fundamental human responsibility, rather than an act of 'playing God.'

She draws parallels between contemporary genetic interventions and historical human actions, such as the domestication of grey wolves into dogs 30,000 years ago or the transformation of teosinte into corn.

The current state of the world is largely a product of human influence, necessitating active management using advanced technologies to ensure the health and survival of species.

This perspective underscores that failing to act is also a decision, one that could lead to a less biodiverse future, emphasizing the ethical imperative to intervene thoughtfully.

By the time the last captive and wild individuals died, the species was thought to be extinct and was on the first list of endangered species in 1966.

The species was rediscovered near Matiti, Wyoming, after a family dog named Shep killed a black-footed ferret, which was then identified by a taxidermist.

An international push initiated a captive breeding program, and every year they can release about 500 black-footed ferrets into the wild, despite challenges with genetic diversity.

Andrew Huberman notes that humanity's comfort with modifying species for immediate convenience often results in long-term detriment to entire populations, highlighting an often-overlooked consequence.

The use of predictive AI and digital twin technologies can significantly improve the modeling of ecological impacts when reintroducing species, offering better, though not perfect, predictions.

While no single human expert can model all the complex variables within an ecosystem, AI systems can process this data continuously, 24 hours a day, 7 days a week.

Colossal Biosciences creates 'care reports' that delve into the potential short, medium, and long-term impacts on ecosystems where de-extinct animals might be released, involving local stakeholders and conservation biologists to consider all perspectives.

To achieve a population of hundreds of mammoths, relying on Asian elephants as surrogates, with their 22-month gestation periods, is not a viable strategy.

The development of artificial wombs would allow for the simultaneous birth of multiple mammoths, bypassing the biological limitations and ethical considerations of using living elephants.

This conservation-driven technology, initially being developed for mice, holds significant potential for human medical applications, such as supporting babies whose mothers require aggressive treatments like chemotherapy during pregnancy.

The creation of a more sophisticated Neonatal Intensive Care Unit (NICU) that leverages genetic understanding and epigenetic research could revolutionize developmental processes, offering exciting and potentially life-saving advancements.

Dr. Beth Shapiro began her academic journey as a broadcast journalism major at the University of Georgia. During her college years, she served as the news director for a local radio station, which involved writing and cutting news for drive-time shows.

After her freshman year, she participated in an honors program class focused on geology and archaeology. This experience, which included visiting archaeological and anthropological sites across the country, led her to consider becoming a science journalist. She subsequently began taking science classes and studying population ecology in Panama.

Later, she applied to graduate programs with the goal of studying inbreeding in wasps. Although she did not receive a Marshall scholarship, she was awarded a Rhodes scholarship, which brought her to Oxford. There, she met Alan Cooper, who was setting up an ancient DNA lab. The opportunity to study ancient DNA, which she saw as a way to combine her interests in geology, paleontology, and storytelling, led her to join the lab and pursue research in Siberia.

Huberman expresses support for her efforts to repair and improve ecosystems.

Huberman distinguishes this work from what he characterizes as 'cutesy' or 'derivative' experiments, such as taking human cells from the cortex and putting them into a mouse cortex, which he believes do not contribute substantial information.

Both Huberman and Shapiro express anticipation that her work will yield positive outcomes for both animals and people.