Is it possible to revive mammoths and other extinct animals

Beth Shapiro researches the DNA of mammoths, dodos and other extinct species. In The Life We Created, she explains how people have interacted with animals throughout their existence: hunted them, domesticated them and protected them from extinction. With the permission of Corpus, we publish an excerpt from the chapter "Intended Consequences" about how scientists are trying to resurrect mammoths.

Most of us who work in the field of ancient DNA are accustomed to questions about the resurrection of extinct species - presumably with the help of biotechnology. Have we already done this? No? So how close are scientists to doing it? Is it even possible to resurrect an extinct species? How is the recovery process? I answer the same thing all the time - no, not yet, hardly in the near future.

Creating an exact copy of an extinct species is impossible and most likely never will be possible.

But there are technologies that someday will probably allow us to revive the components of extinct species - their extinct features.

Let's say a scientist can modify an elephant by adding a piece of DNA that arose during evolution mammoths and elephants will grow hair and develop a thick layer of subcutaneous fat, as a result of which it will be able to survive the Arctic frosts. It is possible to modify the striped-tailed pigeon so that it resembles a passenger pigeon in plumage color and tail shape. But will these modified elephants and striped-tailed pigeons be real mammoths and passenger pigeons? I do not think so.

Why can't we bring extinct species back? There are a thousand reasons why extinct species difficult to revive: from purely technical complexities to ethical questions about the manipulation of species and environmental challenges associated with the need to release resurrected species into an environment where they were not, probably already dozens thousand years. Some technical problems can be overcome (editing the germ line of birds, transplanting an elephant embryo into a captive mother), others are unlikely to ever be solved (restore the intestinal microflora of the extinct woolly rhinoceros, find a surrogate mother of Steller's cow).

Take, for example, mammoths. I know of three research groups that are currently working on recreating mammoths. Of these, two were led by Hwang Woo-seok of the South Korean Suam Biotechnology Research Foundation and led by Akira Iritani of Kindai University in Japan - seek to clone mammoths, that is, to revive them through a process, the most famous result of which was birth dolly the sheep.

Because cloning requires living cells, Hwang hopes to find live mammoth cells that have survived in frozen carcasses, which are now (thanks to global warming) thawing in Siberian eternal permafrost. […] The disadvantage of this method is that there can be no living cells in the frozen mammoth carcasses, since the process of cell decay begins immediately after death. The Iritani working group, however, recognizes that living mammoth cells are unlikely to be found, and turns to molecular biology in order to revive dead mammoth cells, or at least achieve such a semblance of life that they can be clone. Iritani's plan is to force the proteins from the eggs micedesigned to repair damaged DNA, reconstruct broken DNA in mammoth cells.

In 2019, Iritani and colleagues published a paper describing how they tried to do this with cells from a particularly well-preserved mammoth carcass named Yuka. This article was immediately hailed in the popular press as a harbinger of the imminent resurrection of the mammoth, but the evidence seems to suggest otherwise. Although Yuka's cells were remarkably well preserved compared to those of other mummified mammoths, the mouse proteins were not very successful at repairing the cell's DNA.

It is impossible to clone mammoths because all mammoth cells are dead.

A third group that hopes to revive mammoths is led by George Church of the Wyss Institute for Biological Engineering at Harvard University. Scientists admit that it will not be possible to find living cells of mammoths, given that the last mammoths died more than three thousand years ago. However, Church does not agree that this excludes the possibility revive mammoths. He emphasizes that we have at our disposal an endless supply of living cells almost like mammoths - Indian elephants - which can be grown in the lab and transformed from nearly mammoth to fully mammoth with synthetic tools biology. To this end, Church launched a program to use CRISPR to insert DNA into Indian elephant cells. small changes (one at a time) until the cell's genome matches the genome exactly mammoth.

turn genome elephant into the mammoth genome is a task of daunting proportions. The lines leading to Indian elephants and woolly mammoths diverged over five million years ago. Because the mammoth remains are well preserved, scientists working with ancient DNA have been able to reconstruct several genomes from these remains in their entirety. When they were compared with the genomes of Indian elephants, it turned out that they have about a million genetic differences.

Today, it is impossible to make a million modifications to the DNA of a cell at once - none of the available methods for editing the genome allows this. To make so many changes would have to physically break the genome into many fragments at the same time, a potential catastrophe from which the cell is unlikely to recover. In addition, each modification (or set of modifications) requires its own editing mechanism, and attempts to deliver all of them into the cage at once will clearly end in nothing good.

So far, Church's group is doing one or more modifications at a time, making sure they're done. correctly, and then takes the cells with the correct modification and subject them to the next round editing. The last time I asked Church how they were doing, he said that his team had added about 50 modifications, replacing some of the genes with mammoth variants, which studies show make the mammoth look more like a mammoth than an elephant. Today, Church's team has living cells that, if cloned, will contain the genetic instructions that restore some of the mammoth's traits. These are not mammoth cells, but rather mammoth-like.

Is it possible to clone mammoth Church cells? Cloning technologies, especially for domestic animals like sheep and cows, have improved significantly since 2003, when Dolly the sheep was born. However, in the case of other types, a lot of time is spent on clarifying all the necessary details: how and when to pick up eggs, how to create an ideal culture for the early development of embryos, when to implant them with a surrogate mother. And the main obstacle is the stage of reprogramming, at which the somatic cell forgets how to be a cell of its type, and turns into a cell of the type that can become a whole animal. This step rarely gets done right—so rare that the success rate of cloning attempts barely exceeds 20%, even for species that scientists clone all the time.

Elephants have never been cloned, in part because there is no niche market for cloned elephants.

Our clone market domestic animals grows. Biotech company Boyalife Genomics is building a cattle cloning factory in Tianjin and claims to it will be able to raise a million cloned wagyu cows a year to meet the growing demand for Chinese beef. market.

Hwang's company Sooam Biotech is ready to clone your doggy, and in ViaGen Pets, based in Texas, they have a dog, a cat, and even a beloved horse. But for some reason, few people seek to clone their beloved elephant.

It's probably impossible to clone an elephant. Elephants are huge animals with a correspondingly huge reproductive system. This complicates critical steps in the cloning process, such as harvesting an egg for nuclear transfer. and the introduction of a developing embryo into the uterus of a surrogate mother, since the hymen in elephants is between pregnancies regenerates (it has a tiny hole into which the male sperm enters, but for an elephant embryo this is a significant and probably insurmountable obstacle). Indian elephants are also an endangered species, which means that if this technology is still not beyond the capabilities of science, it would be best to apply it to elephant breeding.

Even if elephant cloning becomes technically (and ethically) feasible, it's not entirely clear whether a mother elephant can bear a baby mammoth.

Five million years is a long evolutionary time, and a million differences between DNA is a lot. In essence, the evolutionary difference between mammoths and Indian elephants is about the same as between humans and chimpanzee. It's hard to imagine a chimpanzee mother carrying a human baby (and vice versa).

It has happened that surrogate mothers have successfully produced cubs of a different species, so evolutionary distance may not be a verdict. Domestic dogs gave birth to cloned wolf cubs, domestic cats - healthy steppe cat cubs, and one domestic cow gave birth to a healthy cloned gaur cub.

These experiments proved what scientists suspected from the very beginning: the further the relationship between two species, involved in interspecies cloning, the lower the likelihood of success at each stage of the process cloning. To date, the most distant relatives involved in a successful interspecies cloning experiment are one-humped and two-humped camels (dromedary and bactrian), whose evolutionary paths diverged about four million years ago.

Despite such a long evolutionary period, in 2017, a domestic dromedary camel gave birth to a cloned double humped camel. This is very promising both for bactrian camels (they are almost the first in the list of large mammals endangered), and for conservation. nature as a whole, because this event itself emphasizes how advanced cloning technologies have advanced and how the range of species that can be saved by such methods.

In 2003, a female Iberian ibex was born three years after her species went extinct. Four years earlier, a group led by Alberto Fernandez-Arias, who is now head of the Ministry of Hunting, Fishing and wetlands of the Spanish Autonomy of Aragon, collected the cells of Celia, the last individual of the Pyrenean ibex, and subjected them instant freezingso as not to damage the DNA. Then Fernandez-Arias and his colleagues spent several years developing a strategy for the revival of the mountain goat. They tried to take eggs to clone Celia's cells from other wild mountain goats, but wild animals are not used to people and are great at escaping, so experiment failed.

Fortunately, it was easier to collect eggs from domestic goats. Instead of the DNA of a domestic goat, the scientists introduced the DNA of Celia's frozen somatic cells into the eggs, after which 57 transformed eggs were implanted into surrogate mothers. These cells were hybrids of a domestic goat and a Pyrenean ibex. Seven embryos engrafted and one female was born alive. Alas, the cloned female had a congenital lung anomaly, probably caused by the complexities of the cloning process, and she died within minutes. Attempts to revive the Iberian ibex from Celia's cells have been put on hold, but the cells are still stored frozen.

It is likely that someday scientists will be able to recode the elephant genome into the mammoth genome and clone this a cage by planting it with her mother elephant, however, the process itself can prevent the revival of a mammoth development.

A cloned mammoth born to an elephant mother (or the artificial womb favored by George Church as a solution to the elephant cloning problem) will probably look like a mammoth.

Almost all of us among our acquaintances have identical twins, so we imagine how much DNA affects appearance. But our twin friends are not interchangeable. They have different life experiences, different stressors, different diets and different environments… in short, they are completely different people. Will there be a mammoth that has gone through the elephant path of intrauterine development, raised by elephants, fed on elephant food and possessing elephant microflora intestines, behave like a mammoth - or is it still like an elephant?

It doesn't matter, of course, if our end goal is to create an elephant with some mammoth traits, which is probably what we want. But if we're going to create a mammoth, we also need to recreate the entire habitat of the mammoth, from conception to death. And this environment, alas, also died out.

The book "The Life We Created" also dispels myths about genetic engineering. Beth Shapiro talks about how this trend affects livestock production and helps protect endangered species from extinction.

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