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Cloning. History and essence of scientific discovery

The most important scientific discoveries

Directory / The most important scientific discoveries

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The history of cloning began in the distant forties in the USSR. Then the Soviet embryologist Georgy Viktorovich Lopashov developed a method for transplanting (transplanting) nuclei into a frog egg. He sent the results of his research in June 1948 to the Journal of General Biology. The scientist is out of luck. In August 1948, the infamous session of VASKhNIL took place, where the indisputable leadership in biology of the famous fighter against genetics T.D. Lysenko. The set of Lopashov's article was scattered. Still would! There, the leading role of the nucleus and the chromosomes contained in it in the individual development of organisms was proved. As often happened in the history of Russian science, priority went to the American embryologists Brigge and King, who carried out similar experiments in the fifties.

Further improvement of the methodology is associated with John Gurdon (Great Britain). He began to remove his own nucleus from the frog's egg and transplant into it different nuclei isolated from specialized cells. Later, he began to transplant nuclei from the cells of an adult organism. In some cases, Gerdon's eggs with a foreign nucleus developed to fairly late stages. In one or two cases out of a hundred, individuals went through the stage of metamorphosis and turned into adult frogs. True, they are so frail and defective that one can hardly speak of absolutely exact copying.

However, there was a lot of noise around Gerdon's research. Then for the first time they started talking about human cloning.

As Doctor of Medical Sciences Leonid Ivanovich Korochkin writes, the problem of animal cloning has also become interesting in Russia: "The Mammalian Cloning program was part of the joint work of two laboratories - mine and Academician D.K. Belyaev, who drew attention to the idea of ​​cloning and supported research in this In 1974, I even made a report at the VASKhNIL session, published in the book "Genetic Theory of Selection, Selection and Breeding Methods of Animals" (Novosibirsk: Nauka, 1976) and reported that "at present, the task is to obtain a clone of mammals", and concluded with premature optimism that this task is very difficult, but fundamentally solvable.Our initiatives were initially well funded, but soon the state lost interest in them.The main conclusion we made based on the results that we managed to obtain was the recognition of the futility of nuclear transplantation when trying to get a clone of mammals.This operation turned out to be too traumatic, it was preferable to use the method of somatic hybridization, that is, the transfer of a foreign nucleus by merging an egg with a somatic cell, the nucleus of which was required to be placed in the egg. It was this approach that Jan Wilmuth subsequently used when obtaining Dolly the sheep. By the way, his employee visited the Novosibirsk Institute of Cytology and Genetics of the USSR Academy of Sciences and talked with employees who once dealt with the problem of cloning (this does not mean, of course, that he certainly took advantage of their ideas)."

In the late 70s, Swiss-American Carl Illmensee published an article from which it followed that he had succeeded in obtaining a clone of three mice. And again the clonal boom supplanted all other scientific news, the fanfares sounded again, announcing the fulfillment of mankind's age-old dream of immortality, achievable, however, in a peculiar way - through the artificial production of similar copies of itself. The bitterness of disappointment was not long in coming: rumors spread in the scientific community that something was unclean in Illmensee's experiments, that no one (even the most skillful experimenters) could reproduce them. In the end, an authoritative commission was created, which put an end to the work of Illmensee, recognizing it as unreliable. Thus, a very painful blow was dealt to the problem itself and its solvability was called into question. For a while, calm reigned. And suddenly, like thunder from a clear sky - Dolly the sheep!

In February 1997, it was reported that in the laboratory of Jan Wilmuth in the Scottish city of Edinburgh, at the Roslyn Institute, they were able to clone a sheep. As it became known later, only one experiment out of 236 was successful. This is how Dolly the sheep was born, containing the genetic material of an adult sheep that died three years ago.

The extracted eggs were placed in an artificial nutrient medium with the addition of fetal calf serum at a temperature of 37 degrees Celsius and an operation was performed to remove their own nucleus. Different donor cells were used to provide the egg with genetic information from the cloned organism. The most convenient were diploid cells of the mammary gland of an adult pregnant sheep.

"The developing embryo was cultivated for 6 days in an artificial chemical environment or a sheep's oviduct, tied with a ligature closer to the uterine horn," notes L.I. Korochkin. they may have developed before birth."

A group of scientists from the University of Honolulu, led by Ryuzo Yanagimachi, decided to improve the Wilmut method. They invented a micropipette, with which it was possible to painlessly remove the nucleus from a somatic cell and transplant it into a denucleated egg. Another "know-how" of the Yanagimachi group is the use of relatively less differentiated cell nuclei surrounding the eggs as donors.

The transplanted nucleus, differentiated in a certain direction, and the cytoplasm of the ovum before that worked, as it were, in different modes. To ensure natural nuclear-cytoplasmic relationships between the nucleus and the cytoplasm, they achieved synchronization of the processes occurring in the egg and the nucleus transplanted into it.

The researches of Wilmuth and scientists from Honolulu led, no doubt, to outstanding achievements. But the prospects for their further development should be assessed with caution. It is very difficult to obtain an absolutely exact copy of this particular animal. At least, much more difficult than it might seem at first acquaintance with the problem. The main reason is that the structural and functional changes in the nuclei in the course of the individual development of animals are quite profound. If some genes are actively working, others are inactivated and "silent". The embryo itself is a kind of mosaic of distribution fields of such functionally different genes. The higher an animal is on the hierarchical evolutionary ladder, the greater the specialization of the organism, and the changes are deeper and more difficult to reverse.

“In some organisms,” writes Korochkin, “for example, in the well-known intestinal parasite Ascaris, the genetic material in future germ cells remains unchanged during development, while in other somatic cells whole large fragments of DNA are thrown out - the carrier of hereditary information. In red blood cells ( erythrocytes) of birds, the nuclei shrivel into a small lump and do not work, and from the erythrocytes of mammals, which are evolutionarily higher than birds, they are generally thrown out as unnecessary. In the fruit fly, Drosophila, the processes inherent in other organisms are especially clearly pronounced: selective multiplication or, conversely, a lack of some these are sections of DNA that manifest themselves differently in different tissues.Most recently, it was shown that in somatic cells, during their development, chromosomes are successively shortened at their ends, in germ cells a special protein - telomerase completes, restores them, that is, the data obtained again still indicate significant differences between germ and somatic cells. And, therefore, the question arises whether the nuclei of somatic cells are capable of completely and equivalently replacing the nuclei of germ cells in their function of ensuring the normal development of the embryo.

The already mentioned Carl Illmensee investigated how differentiated Drosophila nuclei are capable of ensuring the normal development of this animal from an egg. It turned out that for the time being the embryo develops normally, but already at the early stages of embryogenesis deviations from the norm are observed, deformities occur, and such an embryo is unable to turn even into a larva, not to mention an adult fly. In the frog, as a creature less developed than mammals, nuclear changes are less pronounced. And at the same time, the percentage of success in cloning, as already noted, is low (1-2 percent) ...

But mammals are much more complicated than frogs in terms of their structure and degree of cell differentiation. Naturally, their success rate will be at least not higher."

In addition, one should not forget about the discrepancy between the conditions of development in the uterus of different adoptive mothers. This means that under different conditions of development of the embryo, the same genes will manifest their action in different ways. Since there are thousands of such genes, the probability of complete similarity of "clones" will not be very high.

Based on this conclusion, experts believe that complete human cloning, for example, is impossible. "Much ado about nothing," said Venter, head of the human genome sequencing project, about the cloning controversy. - You can create a person who will look like your twin, but the likelihood that his character and interests will be the same as yours is close to zero. "It is impossible to 'photocopy' people," the scientist states.

Author: Samin D.K.

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