03 September 2014

Cloning a mammoth – repeat for the particularly intelligent:

"I didn't promise Putin that we would definitely clone"
Why it will not be possible to realize Putin's desire to clone a mammothNadezhda Markina, "Newspaper.

Ru»Vladimir Putin, like all people, is interested in whether Yakut scientists together with South Korean scientists will be able to clone a mammoth.

"Newspaper.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 to revive the woolly mammoth, which is considered the first animal to fall by the hand of man, is very beautiful and ambitious.

Man destroyed the mammoth, now man will return it to Earth. Since scientists have already mastered cloning several animal species and, on the other hand, have mammoth DNA at their disposal, why not clone a mammoth? Yakut scientists who have signed an agreement with South Korean geneticist Hwang Woo Suk are working in this direction.

They are not embarrassed by the scandalous reputation of Hwang Woo Suk, who was convicted of falsifying scientific data on the alleged cloning of human cells. His articles were withdrawn from Science and Nature, and he even received a real term. However, after that, Hwang Woo Suk has been successfully cloning dogs at the Sooam research Center and recently received a US patent for working with stem cells. Scientists from the Northeastern Federal University in Yakutsk in 2012 signed an agreement with the South Korean Sooam Center for the study of the mammoth.

As they told the Newspaper two years ago.En" employees of the Yakut Mammoth Museum, they believe that cloning a mammoth is theoretically possible, although the available technologies do not allow it to be done today.

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

"The probability of finding a living cell is no greater than the probability that a person will take off""Newspaper.

Ru" tried to understand if there are any real prospects for this project. To begin with, let's recall what cloning is. In relation to animals, it is the production of a genetically identical individual from an adult animal cell. To do this, a nucleus with genetic material is taken from the cell and transplanted into a non-nuclear egg, which is then planted to a surrogate mother. A genetic clone is born. After the world-famous Dolly sheep, which, by the way, died prematurely due to accelerated aging, scientists have already cloned quite a lot of different mammals: mouse, goat, pig, cow, cat, dog. The idea to revive extinct animals by cloning has taken hold of the minds of biologists for quite a long time, but so far these attempts have not led to success.

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

The idea of cloning a mammoth is that DNA from mammoth cells of the greatest preservation will be transferred to the eggs of an Indian elephant. It is shown that the Indian elephant, despite its smaller size, is a greater relative of the mammoth than the African one. And it is the Indian elephant that will have the honor to give birth to a mammoth. They also name a specific candidate for cloning – the Malolyakhovsky mammoth, whose remains were found last year on the Novosibirsk Islands. But this is in theory. And what about in practice?

"Although they say that soft tissues and even blood have been preserved in the mammoth remains, it is completely unclear whether there are living cells there," he told the newspaper.En" Doctor of Biological Sciences Sergey Kiselyov, Head of the Epigenetics Department of the Institute of General Genetics of the Russian Academy of Sciences. – And if a cell is dead, then decay processes begin in it immediately, DNA falls apart. Even if a meter and a half of the DNA molecule breaks down at least in half, it will no longer work. The probability that an entire DNA molecule has been preserved in the remains is extremely small. It is as small as the fact that as a result of Brownian motion, all molecules will begin to move upwards, and a person will take off. Do you buy fish at the store? Frozen fish is frozen, thawed, it becomes slimy, because the cellular contents are destroyed. Ice crystals tear the cells apart and if no special measures are taken against the formation of ice crystals during freezing, then they will simply tear one and a half meters of DNA. It is possible to preserve DNA in a dead cell, but only by special laboratory methods."

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

"The second question," continues Sergey Kiselyov, "is how much DNA has been destroyed and will it be possible to collect it? Craig Venter managed to assemble the smallest genome of a bacterium, which is a million times less than we need. For today, this is an unrealizable task."

"How many elephants do you have to catch?"But if mammoth DNA is no good, theoretically there is another way – to take the elephant genome and make it a mammoth genome.

"Theoretically, it could have happened if we all knew how to do it," he tells the newspaper.En" Doctor of Biological Sciences Svetlana Borinskaya, a leading researcher at the Genome Analysis Laboratory of the Institute of General Genetics. – That is, take the elephant genome and enter from it all the mutations that are in the mammoth genome. But technically it's incredibly difficult. It is possible to "promute" several sections 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 huge number of errors. And it won't be the mammoth genome anymore. 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 an elephant is not debugged at all. And the pregnancy of the elephant lasts two years. Dolly the sheep was made from living cells, and about 300-400 embryos were destroyed. But the transplantation of cores on each type requires special debugging. Debugging the transplantation of cores in an elephant is hard to imagine. How many elephants do you have to catch?"

"There is no reason to consider this project technically feasible," Borinskaya believes. – It will take decades, not years, to work out the techniques. However, Nasruddin also said about such projects that either the donkey will die, or the funding agency."

"This lofty goal will allow you to create a lot of necessary and useful things"However, let's imagine, only hypothetically, that all manipulations with DNA were successfully completed, and mammoth DNA was loaded into an elephant egg.

But this is not a guarantee of success.

"The question arises, how much can an egg of another kind be used for a mammoth? – Sergey Kiselyov continues. – In general, it's not working out yet. The most that has been done so far is to transfer genetic material from one to another species in some two species of cats. And this is piece 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 turned out. A baby mammoth was born, which must eat some kind of grass for the development of its microbiota. For him, our microenvironment will be pathogenic, and for us, his microbiota may be pathogenic. And it will be dangerous for him and for us. Well, in addition, it should be borne in mind that the South Korean scientist Hwang Woo Suk, who works with Yakut scientists, has already been caught in falsifications, and it is not known whether this project is another scam of his.

But all this does not mean that it is not necessary to develop cloning technologies, even on mammoths. Be sure to look for ways to create whole genomes. It's like the Great Wall of China, it's like BAM, like a flight into space. It seems that no one needs it, but it moves to feats. This is an idea that will stimulate development. Therefore, it is necessary to set goals such as cloning a mammoth, although we must understand that, most likely, we are not cloning it. But this lofty goal will allow us to create a lot of necessary and useful things on the way to achieve it, which we will use in other things."

"At this stage, the chances are pretty small"About how the work on the revival of the mammoth is progressing, "The newspaper.

Ru" said Semyon Grigoriev, director of the Mammoth Museum in Yakutsk.

– 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 its points are fulfilled. Expeditions are conducted. Last year we unearthed a mammoth that we think is promising for our purposes, the Malolyakhovsky mammoth, with soft tissues, with blood. The Koreans have bought us equipment, and we are opening a laboratory – the International Center for Molecular Paleontology, somewhere in late October – early November. It will work as a center for collective use, open not only to our South Korean colleagues, but also scientists from other countries.

– Have they found living cells in the remains of the Malolyakhovsky mammoth?

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

– Do you think cloning a mammoth is real?

– I think that at this stage the chances of this are quite small. Because it will be very, very difficult to find a living cell even in such a unique material. 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 the other way, but it's a very long way, and the result is clearly not shining 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 can't do it 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 the Indian elephant, it is theoretically possible to obtain mammoth DNA. But then there are a lot of difficulties.

– As far as I know, now the mammoth genome has been decoded by 70%.

– Yes, it was done at the University of Pennsylvania back in 2008, and the assembly was quite dirty. There hasn't been much progress since then. A lot depends on the quality of the material. Many foreign scientists contacted us after the discovery of the Malolyakhovsky mammoth. It's one thing to extract DNA from bone, another thing is 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 fully read the mammoth nuclear genome?

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

– Are you not embarrassed by cooperation with a scientist who was convicted of 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 the Japanese tried to do before him, and he did it. His data was rechecked, and it was proved that all the cloned dogs are really clones. In January of this year, Science and Nature simultaneously published articles where they recognized that he had restored his scientific reputation. This is a rare case when foreigners are ready to invest in Russian science.

– The last question, what did you answer Vladimir Putin to his question 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, come on, clone. I just asked like an ordinary person.

Portal "Eternal youth" http://vechnayamolodost.ru03.09.2014

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