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Is it possible to resurrect a mammoth? Cloning a mammoth. Anfant Terrible genetics

Scientists, led by Dr George Church (pictured) from Harvard University, were able to cut and paste stored mammoth DNA into Asian elephants to create elephant-mammoth hybrids.

Scientists from Harvard have announced that they are ready to clone mammoths based on a DNA framework that is 42 thousand years old. This is necessary to save the Arctic.

Let us remember, over 10 thousand years ago. These huge ancestors of elephants were perfectly adapted to survive in extremely cold temperatures.

Mammoths were a kind of main ecosystem, providing food for predators and exploring the territories of the far north.

That cloning these animals will save the Arctic. At the moment, the unique ecosystem of this geographical area is under threat.

The remains of an individual whose age is about 42 thousand years will serve as the basis for the reproduction of the subspecies.

At least at first, mammoths will live on the territory of a huge safari park. They are planning to be released into the wild later.

The presence in the ecosystem of such large animals that feed on roots and rare greenery will stimulate the tundra to further development. In particular, constant renewal of vegetation will accelerate its growth.

Lyuba, the world's best-preserved mammoth, was exhibited at the Natural History Museum in 2014.

The future population will not be bred in a test tube, but through surrogacy. The happy parent of an entire species will be a female Asian elephant.

Scientists are not ready to estimate the timing of the implementation of the idea, but they are confident that this is already possible today.

Now the researchers are looking for a sponsor who would pay for the gigantic budget of the project.

That they have enough material to begin cloning a female mammoth.

This opportunity arose for specialists due to the fact that in 2013, scientists discovered in the Siberian snows the surprisingly well-preserved remains of an ancient animal that had remained frozen for about 43 thousand years. This news caused wide publicity and immediately attracted the attention of international specialists from the UK, USA, Denmark, South Korea and Moldova, who expressed a desire to help implement this project.

“The data we have collected gives us a high chance of successfully cloning a mammoth,” said Radik Khairullin, vice-president of the Association of Medical Anthropologists of Russia, speaking at a press conference in Yakutsk.

True, the scientist noted here that the research team is not yet ready to play God and understands that this news can cause a wide resonance among the public.

“Before starting work, we must clearly understand the reason why we are going to clone a mammoth. It’s one thing to clone an animal for scientific purposes, but quite another to satisfy your curiosity.”

Khairullin also points out that if cloning does take place, the resulting animal will not be a purebred representative of mammoths, which became extinct four to ten thousand years ago.

“This will not be the same mammoth that lived 43 thousand years ago. To make cloning possible, we will have to use cells from a female elephant, and use the elephant herself as a surrogate mother.”


These remains are more than 43 thousand years old, but they are even better preserved than the body of a person buried six months ago can be preserved.

Victoria Egorova from North-Eastern Federal University says:

“We studied the remains of the soft tissues of the mammoth, and I must admit, we did not expect what we would see. The body of the 43,000-year-old animal is preserved and looks better than the body of a human buried six months ago.”

“When cutting the carcass, we found clear and distinct blood vessels with very strong walls, filled with hemolyzed blood. In enlarged images, we were able to find red blood cells for the first time in such cases. Muscle and fat tissue are also well preserved. In addition, we found migrating lymphocyte cells.”

“The upper part of the carcass was eaten by animals, but the lower part, the paws and, even more surprisingly, the abdominal part, were very well preserved. The liver was not damaged either - it is in very good condition and it looks like there are some solid fragments inside it. We haven’t been able to study them yet, but they seem to be liver stones.”

“We are currently studying the gastrointestinal tract and collecting tissue samples. There's a whole bunch of material here that we'll need to study in laboratory studies."

“Another interesting discovery for us was that in the stomach of the animal we found the remains of plant food, which it ate before its death.”

It should also be noted that the state of the animal’s blood can tell scientists about the circumstances of the mammoth’s death. Radik Khairullin notes that the state and form of the blood can tell scientists that the mammoth died as a result of an unnatural death and had previously suffered for about 16-18 hours. This is also evidenced by the position in which the frozen mammoth was discovered. His hind legs are in an unnatural position.

“We can only assume that the female mammoth fell into an ice hole and was ultimately unable to get out,” says the scientist.

Interestingly, the remains of the animal turned out to be much older than scientists had previously assumed when they were discovered. Initially, researchers believed that the remains were about 10,000 years old, but laboratory tests conducted by Alexei Tikhonov, deputy director of the Institute of Zoology in St. Petersburg, showed that the remains were actually about 43,000 years old.

03 September 2014

“I didn’t promise Putin that we would definitely clone”
Why Putin's wish to clone a mammoth will not be realized

Vladimir Putin, like all people, is interested in whether Yakut scientists together with South Koreans will be able to clone a mammoth. Gazeta.Ru, with the help of experts, tried to assess the real prospects of this project. Yakut scientists hope for success, although they admit that the chances are small. Their colleagues from the Institute of General Genetics of the Russian Academy of Sciences believe that this task is technically impossible.

“I killed you, I will revive you”

The idea of ​​reviving the woolly mammoth, which is considered the first animal to die at the hands of man, is very beautiful and ambitious. Man destroyed the mammoth, now man will return it to Earth. Since scientists have already mastered the cloning of several species of animals and, on the other hand, have mammoth DNA at their disposal, why not clone a mammoth? Yakut scientists are working in this direction, having entered into an agreement with the South Korean geneticist Hwang Woo Suk.

They are not embarrassed by the scandalous reputation of Hwang Woo Suk, who was convicted of falsifying scientific data on allegedly cloning human cells. His articles were retracted from Science and Nature, and he himself even received a real sentence. However, after this, Hwang Woo Sook successfully clones dogs at the Sooam Research Center and recently received a US patent for working with stem cells. Scientists from the North-Eastern Federal University in Yakutsk entered into an agreement in 2012 with the South Korean Sooam Center to study the mammoth.

As employees of the Yakut Mammoth Museum told Gazeta.Ru two years ago, they believe that cloning a mammoth is theoretically possible, although existing technologies do not allow this to be done today.

At the same time, the issue of cloning a mammoth continues to pop up in the news, one way or another related to mammoths. Thus, Vladimir Putin, who recently visited the Yakut Mammoth Museum, also addressed the director of the museum, Semyon Grigoriev. Earlier, Semyon Grigoriev formulated the main task of the Center for Molecular Paleontology that opened in Yakutsk as “the molecular study of mammoth cells under the project “Revival of the Mammoth.”

“The probability of finding a living cell is no greater than the probability of a person taking flight.”

Gazeta.Ru tried to understand whether this project has any real prospects. First, let's remember what cloning is. In relation to animals, this is the production of a genetically identical individual from the cell of an adult animal. To do this, a nucleus with genetic material is taken from a cell and transplanted into a denuclearized egg, which is then transferred to a surrogate mother. A genetic clone is born. After the world famous sheep Dolly, who, by the way, died untimely due to accelerated aging, scientists have already cloned quite a few different mammals: mice, goats, pigs, cows, cats, dogs. The idea of ​​reviving extinct animals through cloning has captured the minds of biologists for quite some time, but so far these attempts have not led to success.

Now about what we know about the woolly mammoth. Its mitochondrial genome was read by Russian scientist Evgeniy Rogaev, and geneticists from the University of Pennsylvania read the nuclear genome of the mammoth in 2008, although 70% of the DNA was fully sequenced.

The idea of ​​cloning a mammoth is that the DNA from the mammoth's cells will be most intact and transferred into the eggs of an Indian elephant. It is shown that the Indian elephant, despite its smaller size, is more closely related to the mammoth than the African one. And it is the Indian elephant who will have the honor of giving birth to a baby mammoth. They also name a specific candidate for cloning - the Malolyakhovsky mammoth, whose remains were found last year on the New Siberian Islands. But this is in theory. What about in practice?

“Although they say that soft tissue and even blood were preserved in the remains of the mammoth, it is completely unclear whether there are living cells there,” Doctor of Biological Sciences Sergei Kiselev, head of the epigenetics department at the Institute of General Genetics of the Russian Academy of Sciences, told Gazeta.Ru. – And if the cell dies, then decay processes immediately begin in it, the DNA falls apart. Even if one and a half meters of DNA molecule breaks down at least in half, it will no longer work. The likelihood that an entire DNA molecule was preserved in the remains is extremely low. As small as the fact that as a result of Brownian motion, all molecules will begin to move upward, and the person will fly up. Do you buy fish in a store? Frozen fish is frozen and thawed, and it becomes slimy because the cellular contents are destroyed. Ice crystals tear apart cells, and if during freezing you do not take special measures against the formation of ice crystals, then they will simply tear one and a half meters of DNA. It is possible to preserve DNA in a dead cell, but only using special laboratory methods.”

Evgeniy Mashchenko, a mammoth specialist at the Paleontological Institute of the Russian Academy of Sciences, has repeatedly said that there cannot be living cells in the remains of a mammoth.

“The second question,” continues Sergei Kiselev, “is how badly the DNA is destroyed and will it be possible to collect it? Craig Venter managed to assemble the smallest bacterial genome, which is a million times smaller than what we need. Today this is an impossible task.”

“This is how many elephants need to be caught?”

But if mammoth DNA is not suitable, theoretically there is another way - take the elephant genome and make a mammoth genome from it.

“Theoretically, this could work out if we could do all this,” says Svetlana Borinskaya, Doctor of Biological Sciences, leading researcher at the Genome Analysis Laboratory at the Institute of General Genetics, to Gazeta.Ru. – That is, take the genome of an elephant and introduce from it all the mutations that are in the genome of a mammoth. But technically it is incredibly difficult. It is possible to “mutate” several parts of the genome, and this has already been done in mice. But no one has done this to change the entire genome, although it would be much easier to turn a mouse into a rat. If we try to do this with the mammoth genome, we will get a colossal number of errors. And this will no longer be the mammoth genome. In addition, we will need to make a diploid genome containing two sets of genes. How to do it?

In addition, an elephant is a very inconvenient laboratory object. And the technology of artificial insemination in elephants is completely undeveloped. And an elephant’s pregnancy lasts two years. Dolly the sheep was made from living cells, and approximately 300-400 embryos were destroyed. But transplanting nuclei on each type requires special debugging. Debugging nuclear transfer in an elephant is hard to even imagine. This is how many elephants need to be caught?”

“There is no reason to consider this project technically feasible,” says Borinskaya. “It will take decades, not years, to perfect the techniques.” However, Nasreddin also spoke about such projects that either the donkey dies or the funding agency does.”

“This lofty goal will allow us to create a lot of necessary and useful things”

However, let’s imagine, purely hypothetically, that all manipulations with DNA were successfully completed, and mammoth DNA was loaded into an elephant egg. But this is not yet a guarantee of success.

“The question arises: to what extent can an egg from another species be used for a mammoth? – continues Sergey Kiselev. – In general, this is not working yet. The most that has been done so far is to transfer genetic material from one species to another in some two species of cats. And this is a piece of material. Let's say that we managed to plant 10 cells, and the elephant's pregnancy lasts two years. Why should everything work out?

But let’s even assume that it happened. A baby mammoth was born that must eat some kind of grass to develop its microbiota. For him, our microenvironment will be pathogenic, and for us, his microbiota may be pathogenic. And it will be dangerous both for him and for us. Well, in addition, you need to keep in mind that the South Korean scientist Hwang Woo Suk, who works with Yakut scientists, has already been caught falsifying, and it is not known whether this project is another of his scams.

But this does not mean that there is no need to develop cloning technologies, at least even on mammoths. It is imperative to look for ways to create entire genomes. It's like the Great Wall of China, it's like BAM, it's like flying into space. It seems that no one needs it, but it motivates them to achieve heroic deeds. This is an idea that will stimulate development. Therefore, we must set ourselves goals such as cloning a mammoth, although we must understand that, most likely, we will not clone it. But this lofty goal will allow us to create a lot of necessary and useful things on the way to achieving it, which we will use in other things.”

“The chances are pretty slim at this stage.”

Semyon Grigoriev, director of the Mammoth Museum in Yakutsk, told Gazeta.Ru about how the work on the revival of the mammoth is progressing.

– You talked to us two years ago, after an agreement was signed with South Korean scientists to work on the mammoth. What has been done during this time within the framework of this agreement?

– Almost all of its points are being fulfilled. Expeditions are being carried out. Last year we excavated a mammoth that seems promising for our purposes, the Malolyakhovsky mammoth, with soft tissues and blood. The Koreans bought us equipment, and we are opening a laboratory - the International Center for Molecular Paleontology, somewhere in late October - early November. It will operate as a center for collective use, open not only to our South Korean colleagues, but also to scientists from other countries.

– Were living cells found in the remains of the Malolyakhovsky mammoth?

– No, research only began in mid-July, the search for cells is now actively underway, but so far they have not been found.

– Do you think that cloning a mammoth is real?

– I believe that at this stage the chances of this are quite small. Because finding a living cell even in such a unique material will be very, very difficult. Although it is possible. But if it doesn’t work out, we intend to look for other mammoths. And if it doesn’t work out again, then go another way, but this is a very long way, and the result is clearly not expected in the next decade.

– Tell us briefly about the second way.

– The second way is to create an artificial DNA molecule based on the modified DNA of an Indian elephant. This is theoretical. Now science cannot do this yet. To do this, it is necessary to decipher the mammoth genome, and knowing the entire sequence of nucleotides, replacing them in the DNA of an Indian elephant, one can theoretically obtain mammoth DNA. But there are still a lot of difficulties.

– As far as I know, the mammoth genome is now 70% deciphered.

– Yes, this was done at the University of Pennsylvania back in 2008, and the assembly was quite messy. Since then there has been no major progress. A lot depends on the quality of the material. Many foreign scientists contacted us after the discovery of the Malolyakhovsky mammoth. It is one thing to isolate DNA from bone, another thing to extract DNA from well-preserved muscle material. But we refused to provide them all with material to work with our Russian scientists from Krasnoyarsk.

– It turns out that your first task is to completely read the nuclear genome of the mammoth?

– No, we are not thinking about the second path now, we are trying to follow the first path. If nothing works out, then there will be another project with another team. Our Korean colleagues are specialists in cloning using the traditional method.

– Aren’t you embarrassed by collaborating with a scientist who was caught falsifying data?

– Hwang Woo Suk is a very great scientist, and his work in the field of animal cloning is not disputed by anyone. For the first time, he managed to clone a dog, which the Americans and Japanese tried to do before him, and he did it. His data was rechecked, and it was proven that all cloned dogs are indeed clones. In January of this year, Science and Nature simultaneously published articles acknowledging that he had restored his scientific reputation. This is a rare case when foreigners are ready to invest in Russian science.

– Last question, what did you answer to Vladimir Putin when he asked about cloning a mammoth?

– I answered as it really is, that we are working in this direction together with South Korean scientists and that we hope for a positive result. I didn't promise him that we would definitely clone. And he didn’t say anything, like, yeah, guys, let’s clone. I just asked like an ordinary person.

Until relatively recently, 2 million - 10 thousand years ago, completely different animals lived on Earth. Saber-toothed tigers, woolly rhinoceroses, cave bears, primitive bison, and mammoths roamed the expanses of Eurasia. But they all became irretrievably extinct; today they can only be seen in a picture or in a museum.

Many of us would like to see live an animal from the past, for example, the mammoth - the hairy giant of the Ice Age that finally disappeared from the face of the Earth about 10 thousand years ago. Scientists have long declared their intention to resurrect this extinct animal. How far have they progressed in their work and how soon will we see the newborn baby mammoth? Why are mammoths needed today?

Genetic engineering at the service of “resurrectionists”

Modern science knows several ways to resurrect the woolly giant.

Method one - a mammoth can be cloned. To do this, it is necessary to find the remains of an animal in the permafrost, extract the preserved nuclei from the cells, “pull out” the DNA from them, insert it into the egg of an animal of a related species, obtain an embryo and place it in the uterus. Then it’s up to the surrogate mother.

Scientists from Russia and South Korea are following this path. Specialists from the North-Eastern Federal University are looking for the preserved remains of mammoths and are trying to isolate DNA from the animal’s tissues. Representatives of the Korean Biotechnology Research Foundation Sooam Biotech are deciphering DNA and sharing advanced cloning experience with Russian scientists.

As part of this project, the international center “Molecular Paleontology” was opened in Yakutia in 2015, whose employees study the cells and DNA of mammoths and other ancient animals. Over the past few years, scientists have reported no major progress in their work. This is probably due to the fact that the chances of finding a mammoth cell with a surviving nucleus are extremely low.

Method two. In order for a baby mammoth to be born, it is necessary to create artificial DNA. This became possible thanks to the replacement of fragments of the genome of a related animal, carried out using the CRISPR/CAS genome “rewriting” technology that appeared in 2012. The latter makes it possible to carry out various manipulations with genes - to change and delete arbitrary genes in the DNA of mammals in a targeted manner.

A research group from Harvard University (USA), led by Professor George Church, followed this path. Scientists decided to insert mammoth genes into the DNA of the closest related animal - the Indian elephant. To do this, you need to isolate DNA from mammoth tissue, determine which genes are responsible for important characteristics of the species, and then “cut out” them and place them in the DNA of an elephant’s somatic cell. Next, you need to get an embryo from this cell and carry it out, again with the help of a surrogate mother or an artificial uterus.

In 2015, Harvard scientists were able to isolate 14 mammoth genes and insert them into the DNA of an elephant skin cell, where they functioned as normal DNA components. The genes used were those responsible for the typical characteristics of a mammoth, which help the animal withstand extreme cold - long hair, a thick layer of subcutaneous fat, small ears and hemoglobin. The scientists were then able to propagate cells with this “mosaic” DNA.

Now scientists need to turn the resulting cells into tissue and make sure that changes in genes lead to the desired result. Then the animal's organs will be formed from the tissues and an artificial embryo will be created. The latter is planned to be implanted into the uterus of a surrogate elephant mother or into an artificial uterus. Professor Church prefers the latter option, since in this case the female individual of an endangered species would not have to be put at risk. Church and his research team plan to share the latest results of their work with the public in the summer of 2017.

Some scientists believe it is possible to recreate the entire mammoth genome. Ancient DNA expert Beth Shapiro from the University of California (USA) claims that resurrecting a mammoth is quite possible. The remains of mammoths used by scientists are well preserved, having lain in a frozen state for more than 30 thousand years.

Half-mammoth, half-elephant

If scientists from Harvard manage to implement their plans, then, unfortunately, there will be no need to talk about the real resurrection of the mammoth. What may be born as a result of the painstaking work of American geneticists is a hybrid of a mammoth and an elephant, that is, in fact, a mammoth-like elephant that can live in an Arctic climate.

It was the Asian elephant, the closest relatives of mammoths, that was chosen to “resurrect” the mammoth. They take their origin from a common ancestor who lived on Earth 2.5–5 million years ago. In addition, the Asian elephant is a critically endangered species.

If successful, Professor Church plans to “resurrect” many female and male specimens and keep them in an open park area with adjacent office premises. They will carry out the necessary veterinary procedures and carry out further research.

If the young survive, the scientist would like to place it in a place where there are almost no people yet. In this way, he will be able to expand the habitat of proboscis animals and help save the species from extinction. Professor Church dreams of populating northern Canada and Siberia with elephant-mammoths. He believes that "resurrecting" large animals will help stabilize the tundra ecosystem, which is threatened by thawing permafrost, and preserve dwindling carbon reserves.

The fact is that the soil of Siberia accumulates the largest reserve of greenhouse gases on Earth. The amount of carbon dioxide and methane that will be released if the tundra begins to melt exceeds the amount of carbon contained in the atmosphere and in all the forests of our planet. But what do mammoths have to do with it?

A group of Russian ecologist Sergei Zimov conducted experiments in Siberia aimed at imitating the behavior of mammoths. When mammoths move on a snowy surface, they break through the snow and let cold air into it. Scientists used tanks to fell trees, just as mammoths did in the past and elephants do today. In winter, falling trees whip up the snow, thereby increasing its insulating properties and stabilizing soil temperature, and in summer they increase solar reflection coefficient. During the experiments, it was discovered that the soil temperature in the experiment sector was 20 degrees Celsius lower than the soil temperature in neighboring areas not affected by the experiment.

The other side of "resurrection"

The biological material used by Church's group comes from the remains of mammoths found on Wrangel Island, the last refuge of the extinct animals. There is a theory according to which diseases provoked by inbreeding played a significant role in the extinction of the population of mammoths that inhabited this island.

Some scientists believe that Church's project is doomed to failure, since if he and his colleagues do manage to create an elephant-like mammoth, it will be susceptible to the diseases that his ancestors suffered from. Professor Church himself does not share the skepticism of his opponents and claims that his group uses corrected, healthy alleles of mammoth genes and constantly checks the results.

Professor Matthew Cobb from the University of Manchester (UK) expresses concern that if scientists manage to grow an embryo in an artificial womb, the resulting animal will be deprived of prenatal interaction with its mother and this will negatively affect its psyche. In addition, it is unclear whether elephants will accept a newborn as “one of their own”: mammoths and elephants are social animals, and active interaction with other individuals of their species is important for them.

Let us add that the very idea of ​​​​restoring species that have long disappeared from the face of the Earth finds many opponents. For example, Professor Hugh Possingham from the University of Queensland (Australia) believes that the “resurrection” of lost species could lead to further loss of biodiversity, since the cost of resuscitating dead species greatly exceeds the cost of preserving existing species.

LiveScience correspondent Stephanie Pappas notes that if the New Zealand government were to fund the “resurrection” of 13 extinct animal species and their maintenance, then it would have to abandon the idea of ​​funding conservation programs for the 33 species that are now at risk of extinction.

Nevertheless, if the American project to “resurrect” the mammoth is successful, the newborn baby mammoth will, without a doubt, mark a new stage in the development of science. Let's hope that if the animal is actually born, it will not only satisfy our idle curiosity, but will also be able to bring real benefits to humanity in the fight against global warming and for the preservation of biodiversity.

MOSCOW, July 13 – RIA Novosti, Alfiya Enikeeva. Technologies of cloning, DNA sequencing and cell reprogramming make it possible to resurrect extinct animal species. RIA Novosti tells how far technology has advanced, why the mammoth has not been cloned yet, and who scientists are going to revive in the future.

In March, when the last male northern white rhinoceros, Sudan, died, experts said that these animals would soon disappear forever, since only two individuals remained in the world - females Najin and Fatu. However, the other day they reported that the population can be restored. Using the latest reproductive technologies, European biologists created a “hybrid” embryo by combining sperm taken three years ago from Sudan with eggs from his normal African relatives.

Now scientists are going to take eggs from the last two females and get purebred embryos. The cubs will most likely be carried by surrogate mothers from the South African white rhino population. Thus, the northern subspecies will recover, biologists are sure.

What n e X wobbles d la at hasty To cloning

Mammoth clone in Yakut: “living” cell in exchange for technology from KoreaOn Tuesday, the results of the expedition were summed up, searching for the remains of mammoths in the permafrost suitable for cloning. The expedition found several bones, including one with bone marrow, where one apparently intact cell nucleus was discovered. This became the reason for the sensational news that cloning a mammoth is now a matter of technology.

It will not be possible to resurrect other extinct species so quickly. Cloning using classical technology, when the nucleus of a living cell is inserted into an egg, is impossible . In the soft tissues of mammoths, even very well preserved (found mainly in Yakutia), there are no such cells. Moreover, even in ideal permafrost storage conditions cells, and therefore DNA, are destroyed.

Evolutionary biologist and ecologist Ben Novak of the independent research organization Revive & Restore intends to give a second life to the passenger pigeon (Ectopistes migratorius) by 2025. The last representative of this species, which existed back in the days of mammoths (the oldest remains of these birds are hundreds of thousands of years old), died in 1914.

Biologists from the Palaeogenomics Laboratory at the University of California, Santa Cruz, with whom Revive & Restore is collaborating, obtained nuclear DNA from four preserved pigeon carcasses and mitochondrial DNA from 41 samples. So Novak has something to work with.

Reconstructing and deciphering the DNA of the Mauritian dodo, or dodo (Raphus cucullatus),

© CC BY 2.0 / Federico Moroni

And yet, deciphering the genome is one thing, but finding entire nuclei with unbroken chromosomes is quite another. Therefore, many do not share the enthusiasm of supporters of the idea of ​​​​resurrecting extinct animals. Additionally, recreating and maintaining populations in the wild would be very expensive. Scientists from the University of Ontario point out that the choice in favor of the mammoth and other ancient animals will be fatal for many of today's endangered species, since there are insufficient resources for ecological conservation of both.

 


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