On February 22, 1997, the world learned about the existence of Dolly the sheep - the first warm-blooded animal cloned using a conventional somatic cell. How the bold technology was developed and whether it has a future.
In the age of rapidly developing technologies, the issue of cloning - the reproduction of individuals genetically identical to the parent organism - becomes truly acute and controversial. But talking about cloning as something fundamentally new and unnatural is wrong. In nature, reproduction through the reproduction of genetically identical individuals is a very common phenomenon. Bacteria simply divide in two, fungi, algae and some other organisms multiply by spores, and some insects and even vertebrates can develop without the participation of male germ cells, only with the help of female ones. In all these cases, the child organism is a clone of the parent. Not bypassed the process of natural cloning and humans: identical twins have exactly the same sets of genes.
The scientists decided to reproduce this process on their own. Of course, it was not about creating an army of clones, but about raising animals and plants with certain useful qualities. Agriculture, light industry, medicine would develop faster if cloning was put on stream. Plants themselves perfectly reproduce their copies, man can only control the process, but the issue of accurate reproduction of animals for a long time remained very problematic.
The cell that gives life
The answer to it was found closer to the middle of the last century. Scientists decided that for cloning, you need to take a zygote (fertilized egg) from one animal, remove genetic material from it and insert the nucleus of a somatic (non-reproductive) cell of another animal. During natural sexual reproduction, the daughter organism receives a single set of genes from the father's germ cell and the same from the egg. A clone at the time of its creation also receives a double set of genes, but only from one parent. True, the resulting organism will not be a complete genetic copy: in each genome there is a certain number of random mutations, which do not coincide even in clones.
But mutations are not the main problem that scientists faced in the middle of the 20th century. The fact is that any cell of the body, except for the reproductive cell, is somatic, and any cell of the body has its own differentiation. In other words, only those genes work in each cell that it needs to perform "official duties" that are different for each organ. The researchers feared that by transplanting such specialized genetic material into the zygote, they would create an unviable clone. These doubts were dispelled by John Gurdon, after in 1962 he was able to clone a frog in the described way.
Biologist John Gurdon
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Reuters
True, some scientists considered the experiment not entirely clean, because Gurdon used tadpole cells. Eight years later, in 1970, he was able to repeat the same experiment, but with adult cells. The clones survived. Thus, scientists have made a defining discovery in the field of cloning: specialized somatic cells can give life to a new organism.
Mouse and three sheep
So the way was opened for cloning mammals. However, everything did not go so smoothly here: for many years, researchers from different countries could not repeat Gurdon's experiment on more complex animals. Then they decided to simplify their task: they placed not the nucleus of a somatic cell into the zygote, but an embryonic cell. Scientists from two countries have achieved success here: Soviet geneticists created the mouse Masha, and the British - the sheep Megan and Morag.
So why couldn't you create a clone using somatic cells? After the first failed experiments, scientists decided that it was simply impossible to conduct such an experiment with mammals; this opinion prevailed in the scientific world almost until the end of the 20th century. And then Dolly appeared at the University of Rosslyn (Great Britain) - the first mammal obtained as a result of the fusion of an egg and a specialized somatic cell. So what did Jan Wilmuth's group change in the experience so that Dolly could be born?
Embryologist Ian Wilmut
Reuters
The researchers changed the technology quite a bit: instead of a zygote, they used an unfertilized egg.
But even these changes did not lead the group to absolute success. Dolly emerged from one of 277 eggs; 28 of her twins managed to develop into embryos, and only she was born. It is unlikely that such a technology can be called successful and put on stream, but at the end of the 1990s, this was not what scientists were thinking. The main point was to prove that mammals can be cloned using a somatic cell. From this point of view, Dolly's appearance was a tremendous success.
ID number 6LL3
The sheep was born on July 5, 1996 under the name (more precisely, number) 6LL3. The idea to give the first mammalian clone the name Dolly came to the minds of farmers who looked after the sheep's surrogate mother (her real mother died three years earlier; the genetic material used was frozen and carefully preserved until better times).
They found it funny that 6LL3 emerged from a cage taken from an udder, so they named the new sheep the name of Dolly Parton, a country singer who owed her fame in part to the large bust.
The sheep lived six years and gave birth to six lambs. True, six years is not enough for sheep, which, as a rule, die at the age of 10-12 years, but according to the official version, Dolly's death has nothing to do with the consequences of cloning: for two years the sheep suffered from arthritis, and at the end of its life it also caught severe pulmonary virus. On February 14, 2003, one of the most famous animals was euthanized.
Dreams of Jurassic Park
But Dolly did not become famous right away: the world found out about her existence only seven months after her birth, on February 22, 1997. All this time, scientists were receiving a patent for a nucleus transfer technique, so they could not announce their incredible success in the press. But Dolly's twin sisters did appear. In 2016, 13 of them have already reached a respectable age of seven to nine years. The technology, which at first was not very effective, was refined, which made it possible to conduct experiments on other domestic animals.
One of the main goals that scientists are pursuing now is the "revival" of extinct species. The pioneers in this area were Spanish researchers: in 2009, they cloned a Pyrenean goat, which disappeared from the face of the earth nine years earlier. Scientists were lucky: in the Research Center for Agriculture and Technology of Aragon, the genetic material of the animal was preserved, which was used in cloning. The success of Dolly the sheep, however, could not be repeated: the clone died 7 minutes after birth due to a congenital lung defect.
Many scientists believe that it is too early to talk about the cloning of extinct species. First, even if it is possible to extract the DNA of an extinct animal from the remains, it is unclear what to do with the egg. The Oxford group is trying to solve this problem with a related egg cell. Researchers are working on the resurrection of the Dodo bird, which disappeared at the end of the 17th century. They found out that the closest relative of this large flightless bird is the pigeon, and more specifically the Victoria crown pigeon, or saw-billed pigeon. The consistency of the Oxford theory remains to be seen.
Secondly, it is unclear how the extinct organisms will react to the changed environmental conditions. Skeptics believe that the organisms of the clones will not be able to adapt even to the modern composition of the atmosphere and will die.
But such concerns should not stop scientists. The scientific community cannot say for sure how specialized somatic cells become life-giving cells, or why an egg should be used in cloning rather than a zygote. Anticipating the reaction of nature to the reproduction of extinct species is a thankless task. No doubt is worth giving up trying.
Yulia Popova