26 May 2022

Vain efforts: details

Why the revival of extinct species is impossible (but useful)

Yasemin Saplakoglu, Quanta Magazine: Why ‘De-Extinction’ Is Impossible (But Could Work Anyway)

Translation: Ekaterina Shutova, XX2 century

There are several projects aimed at reviving mammoths and other species that have disappeared from the face of the Earth. Moreover, the fact that it is technically impossible does not matter.

For scientists investigating extinct species in an ambitious quest to bring them back to life, a publication published in March in the journal Current Biology (Lin et al., Probing the genomic limits of de-extinction in the Christmas Island rat) was a sobering collision with reality. A group of researchers led by Thomas Gilbert, a genomics specialist and professor at the University of Copenhagen, tested the possibility of species resurrection. To do this, scientists sequenced the genome of Maclear's jerboa mouse from Christmas Island (Australia) — a species that became extinct in the late XIX or early XX century.

"It seemed like the perfect plan," Gilbert shares. DNA samples of an extinct species are relatively fresh and well preserved. In addition, rodents from Christmas Island (Rattus macleari) are genetically very close to the gray rat (also known as Rattus norvegicus, Norwegian rat). And the DNA of the gray rat is well studied. This is not the same as trying to reconstruct the DNA sequence of some ancient cat from the Pleistocene jungle. Not to mention the dinosaur. With the reconstruction of the genome of a recently extinct close relative of an ordinary rat, there should not have been any special difficulties.

However, in fact, everything did not go so smoothly. Despite all efforts, scientists have failed to restore about 5% of the genome of the jerboa mouse from Christmas Island. Many of the genes that could not be read were related to the sense of smell and the immune system — two insanely important functions for animals. "These are not some insignificant things that don't have to be restored," Gilbert explains. "Without them, you will get a species unlike the one that is extinct."

De-Extinction.jpg

Representatives of extinct species: thylacine (Tasmanian wolf), quagga, dodo and Maclear's jerboa mouse from Christmas Island.

Yes, the results of Gilbert's team are new. But in many ways they only confirm what many scientists have long guessed. According to Beth Shapiro, professor of ecology and evolutionary biology at the University of California at Santa Cruz, "the biggest misconception about the rebirth of species is that this rebirth is possible."

Ben Novak, a senior researcher at Revive & Restore, one of the main non-profit projects for the revival of species, readily admits this. "You can never bring back what's extinct," he says. But for him, as for most other scientists involved in the revival of species, getting not real extinct animals, but only similar to them is not a problem, but a goal.

Most researchers who are engaged in the revival of species are not trying to resurrect charismatic ancient animals to put them in the nearest zoo to the delight of the public. Scientists rather seek to create something approximately similar for educational and environmental purposes. For example, to fill the "void" left by extinct species in ecosystems. Or to increase the number of modern endangered species.

Assembling the genome piece by piece

The problems facing species revival projects begin with DNA, a molecule that seems to give hope that extinct animals will walk the Earth again. In the novel "Jurassic Park" and the film series of the same name, the DNA of a dinosaur more than 65 million years old is extracted from a mosquito preserved in amber. But in reality, DNA is too fragile a molecule to last that long. The half-life of DNA is only about 521 years.

Even in well-preserved tissues that remain from recently extinct species, DNA is often fragmented. "And due to the fact that these fragments are too small, they cannot be assembled [electronically], like pieces of a puzzle, into a complete picture, which they were before," Novak comments.

In particular, it is not always clear in what order the genes should stand in the reconstructed DNA molecules. Such details are important because studies on living species have shown that small changes in the gene sequence can significantly affect the behavior and other characteristics of organisms. Yes, researchers who are engaged in the revival of species usually use close relatives of extinct animals as a guide. However, this approach has limitations.

"Even if we had 100% of an organism's genes, we would still create it with the same gene order and number of chromosomes as its living relative," Novak shares. And, as Gilbert's new work clearly shows, it is often simply impossible to get close to the entire genetic sequence.

The work of Gilbert's team speaks about the difficulties of reviving extinct species with the help of genetic engineering. Genetic engineering is a popular approach favored by researchers such as George Church, professor of genetics at Harvard University. Church is leading a project aimed at bringing back the woolly mammoth that roamed the Earth in prehistoric times. Recently, Church's project received additional funding from the startup Colossal — and thanks to this, the scientist hopes, in the next decade or so his team will succeed by editing the genome of the Asian elephant, a close relative of the mammoth.

However, the revival of extinct species is something more than just genetic engineering. Using an approach called breeding back, or breeding rewilding, some scientists are restoring ancient traits of extinct species by selecting and breeding individuals who still carry the corresponding genes. For example, the task of the Tauros Program is aimed at "returning wildness" crossing breeds of modern cattle bearing ancient, wild traits, so that their offspring look more like their non—domesticated ancestor - tura. And scientists from the South African Quagga Project are selecting zebras with features of the quagga subspecies, hunting for which led to its complete extinction in the XIX century.

Nevertheless, even if the efforts of genetic engineers and breeders are crowned with success, they will receive not an extinct species itself, but a kind of hybrid.

If we want to create the most accurate copy of an extinct species, we need to grow a clone from a live or specially preserved cell of this very species. Scientists do not have usable cells of woolly mammoths, dodos, Tasmanian wolf and most other "unpeeled" extinct species. However, there are cells of other animals that have recently become extinct. So, in 2003, experts used cloning in an attempt to revive Bucardo, an extinct species or, according to another classification, a subspecies of the Pyrenean goat. A modern goat became a surrogate mother and egg donor. Unfortunately, Bucardo the goat, a representative of the only extinct species that has ever been cloned, died just seven minutes after birth due to a lung malformation.

But even having once achieved real success in cloning extinct species, scientists, according to experts of the International Union for Conservation of Nature (IUCN), can reveal to the light "almost twins" who will differ from extinct forms in an unpredictable and unknown way. For example, scientists may not be aware of all the potential epigenomic differences affecting DNA activity or the microbiome needed to maintain animal health. In addition, scientists will not be able to accurately recreate the environment in which the original species learned to live. And as a result, the behavior of "almost doubles" will differ from the behavior of the originals.

However, despite these possible differences, Novak believes, "from an evolutionary point of view, a clone is an authentic, or 'authentic', reborn organism." In fact, although cloning is included as a promising method in the IUCN guidelines, Novak believes that it (even if some researchers disagree with this) should be considered as a way not so much of a real revival of species as their "reliable restoration".

Functional equivalents

Yes, there are problems in the field of species regeneration. However, scientists working in this field do not retreat. For them, a successful "almost double", an intermediate variant between a living and extinct species or a functional equivalent of an extinct species is a success. "I do not know anyone who would talk about the need to get someone's exact copy," Church shares. The practical goal of the woolly mammoth revival project, which he directs, is to help endangered Asian elephants adapt to the cold conditions of the Arctic tundra.

"Rest assured: scientists do not think they will get a mammoth. Because they won't get it," Gilbert adds. Scientists will get a "woolly elephant" that can live in the cold.

A hybrid of an elephant and a mammoth can be "populated" in places such as the Pleistocene park — a huge tundra territory in Russia, where scientists are trying to restore an extremely biodiversity-rich and climate-friendly pasture ecosystem that was once inhabited by large herbivores, including mammoths. Trampling the soil, elephant mammoths would allow cold air to seep into its thickness — thereby, in theory, slowing the melting of permafrost. It is assumed that greenhouse gas emissions would also slow down as a result. Scientists who are working on the creation of hybrids hope that the bonus will also save elephants from complete extinction — after all, genetically engineered hybrids will live in a spacious territory free from human conflicts.

In the same way, Novak is now working on the revival of the wandering pigeon and the heather grouse — genetically modifying modern species. He hopes that genetically engineered hybrids will help restore the affected ecosystems and inspire humanity to make more efforts in this direction.

The staff of the San Diego Zoo (California, USA) are trying to save the northern white rhino, a species that is functionally extinct because there are only two females left in the world. Scientists have obtained pluripotent stem cells from the frozen tissues of the northern white rhinoceros — now we need to encourage them to differentiate into sperm and eggs and get embryos. The surrogate mothers for them should be the females of the southern white rhinoceros living in the Rhino Rescue Center of the safari park owned by the zoo.

Beth Shapiro shares: "I am excited by the idea of the revival of species. And I continue to talk and give interviews on this topic not because I think that we will really revive the mammoth. I don't think we will revive it. But what is being done along the way is important for the preservation of those who have not yet died out."

And if, one way or another, the restored species can be reintroduced into the wild, into the corresponding ecosystems, in the long term, this success can develop naturally. "If we make our "almost doubles" sufficiently similar to the originals," Novak summarizes, "evolution may eventually bring them closer to their original forms better than this can be achieved artificially in principle." In case, of course, if the forces that led to the disappearance of the "originals" do not destroy the "doppelgangers".

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