July 5, 1996 – an unremarkable summer day. But for embryologist Jan Wilmut and colleagues from Roslin University (Scotland) he became one of the main in their life. On this day, the long and painstaking work of scientists ended with success. “Success” was an ordinary sheep of the Finn-dosert breed, which appeared that day in the university vivarium. Sheep at birth was given the number 6LL3. Only then one of the veterinarians who worked in the Wilmut team offered a name for the lamb – Dolly, in honor of the singer Dolly Parton. The sheep did not differ from other animals of the same species, except for one small detail: Dolly was a clone of another adult sheep.
The world learned about this event only on February 22, 1997, when Wilmut et al published in the journal Nature the article about the birth of Dolly and the way of her cloning. This news was one of the main events of the year and sparked heated discussions in the society. Dolly was probably one of the most recognizable animals in the world. And although now the excitement around cloning is not so strong, but Dolly left a big mark both in science and in public life.
What is Dolly’s unique sheep?
My very unrepresentative survey of friends and colleagues showed that no one really had thought about this issue. The answers were standard: either “first cloned organism,” or “first cloned animal,” or “first cloned mammal.” The same situation is happening in most media covering the topic of cloning. To put it mildly, all these answers are rather inaccurate. But to understand this, you need to study theory.
What is a “clone”? In fact – a genetic copy of the parental organism. Based on this definition, we can say that nature has long been “engaged” in cloning, beginning with fissionable bacteria. Also natural cloning can be called parthenogenesis.
Man is engaged in cloning for economic purposes, too, a very long time, primarily in agriculture. The simplest example is the cultivation of potatoes from a tuber with ocelli or the propagation of strawberry with antennae. In both cases, we get organisms that are genetically identical to the original. So Dolly is clearly not the first cloned organism.
Cloning animals also exists in nature. For example, all the same parthenogenesis, more precisely – ameotic parthenogenesis, when the egg of the female remains with the standard double set of chromosomes and begins to develop into a new individual. About division and budding, I’m already silent. If we take the cloning of animals that are incapable of parthenogenesis, then in 1962 John Gerdon from Oxford stated that he could clone a South African frog. And the following year the Chinese Tong Dizhou first cloned fish – Asian carp.
Only the first cloned mammal remains. But the ill luck – the first clone of a mammal – by the way, also a sheep – was obtained back in 1984 by the Danish scientist Sten Villadsen. That is, here Dolly is not the first.
But why so much noise? It’s all about the cloning process. But first, let’s take a deep look at cell biology.
Already from the school course of biology, we learn that our organisms are composed of many cells. They differ in form, structure, functions. But at the same time they all develop from one single cell – a fertilized egg. How does this happen? It’s all about the potency of cells – their ability to evolve into other types of cells. By the potency of the body cells can be divided into two groups – nondifferentiated (pluripotent and totipotent) and differentiated (unipotent). Undifferentiated cells are characterized by the capacity for infinite division and the ability to transform during the course of reproduction into cells of different species. Among the undifferentiated distinguish between totipotent and pluripotent cells. The first can develop into any cells of the body (an example is a fertilized egg),
Differentiated cells are, in fact, the final stage of development of undifferentiated cell lines. They are normally limited number of divisions, and all descendants of a differentiated cell will be identical in structure and functions. For example, the epithelial cell will, in dividing, form a new epithelial cell, but not a neural and not a muscle cell.
During the first experiments on cloning, scientists used the genetic material of amphibians and fish, transplanting the nuclei of differentiated cells of these organisms into non-nuclear oocytes. And everything went well until the biologists moved to cloning mammals. And here the problems started. At first, the mammal’s ovum was small compared to the egg of the same frog. This problem was solved by improving the technique of manipulating cells. But then … Transplantation of the nuclei of differentiated cells into mammalian ovules led to the fact that the zygote ceased to divide (or did not start at all) and the development of the embryo stopped. That is, a simple nuclear transplant did not give the desired result. We began to experiment with the nuclei of embryonic cells and found out. that after a certain number of divisions, the blastomeres lost their totipotency and turned into pluripotent cells whose nuclei were also not suitable for cloning. Therefore, the first mammals were cloned from blastomeres obtained from embryos at early stages of development (usually 8 or 16 cell embryos). Well, they also thought in parallel how to get around this unexpected obstacle.
And it was possible to do it just to Jan Wilmut and his colleagues. Sheep Dolly was obtained as a result of a transplantation of the nucleus of the epithelial cell of the breast. Thus. it became the first mammal to be obtained using the genetic material of a differentiated cell. By the way, a funny fact. As already mentioned, the sheep was named Dolly after the singer Dolly Parton. Apart from creativity, the singer was famous for her outstanding bust, as well, as Dolly’s sheep was born from the cage of the udder, and such an association came to the veterinarians.
However, in reality everything turns out to be more complicated. It is worth mentioning at least the fact that Dolly was the only one of the 277 embryo-clones that could develop into a full-fledged individual. For a while, there were even speculations about fraud and forgery from Wilmut. Like, instead of the nucleus of the cells of the epithelium of the breast, scientists accidentally or intentionally introduced the nucleus of an undifferentiated cell. However, further research and improvement of the cloning process showed that Wilmut’s method works.
It is worth noting that some commentators do not consider Dolly a complete clone. The fact is that in nuclear cells the genome, in addition to the nucleus, is also stored in the mitochondria, the organelles of the cells responsible for the energy exchange. That is, Dolly had in fact two genomes: one (nuclear) – from the donor of the nucleus, the other (mitochondrial) – from the donor of the egg. But in general, this is already nit-picking.
Life and death of a sheep.
After the birth, Dolly developed as an ordinary sheep. She even managed to give birth to six lambs. Scientists feared that close attention to the sheep could harm her and left her in a stall that eventually killed her. First, Dolly began to develop arthritis, which was the result of inadequate exercise and hypodynamia. But this actor was successfully treated with anti-inflammatory drugs. Then Dolly picked up the JSRV virus, which resulted in a progressive lung disease. On February 14, 2003, Dolly had to be put to sleep due to the severity of her illness. Scarecrow Dolly is exhibited at the Royal Museum of Scotland.
The death of Dolly caused controversy regarding the safety of cloning. There were fears that such an early death of a sheep is caused by the rapid aging of the body. For fairness sake, it should be noted that the connection of arthritis with the rapid aging of the animal was simply expressed at a conference, and then a simple assumption by the method of a “spoiled phone” turned into an “irrefutable fact.” However, in July 2016, the journal Nature published an article by K. Sinclair of the University of Nottingham (UK), in which he reported on the life of 4 clones already Dolly, obtained by transferring the nucleus from the cells of the breast to the egg. The clones appeared in 2007, ie. At the time of publication of the article, they were 9 years old, which clearly exceeded the age of Dolly’s death. At the same time they developed as well as ordinary animals.
Scandals, intrigues, investigations.
As I mentioned, the birth of Dolly caused a violent social reaction. The spectrum of opinions was wide: from “the future has come” to “the end of the world is approaching.” Suddenly it turned out that the book fantasy was not so fantastic. The cloning technology was still too raw, but rumors of cloning people immediately began to spread.
And here the Clonage office came to the fore. Its representatives said that they would begin experiments on human cloning. In 2003, they announced the birth of the first child clone, called Eva. Here are just no evidence of this event, they never showed. Also, serious doubts about the activities of this firm cause her connections with the sect of raeliths. The funny thing is that representatives of the company still from time to time report on the next cloning of a person. Only show clones has not yet been obtained.
A number of countries have developed their own legal acts regulating cloning issues. In 2005, the UN called on countries to enact laws prohibiting any kind of cloning. Some countries (including Russia) suggested leaving the therapeutic (for obtaining stem cells) cloning at the discretion of each state separately. A number of countries have introduced into their criminal codes articles criminalizing the cloning of people.
In Russia, there is an unlimited moratorium on human cloning. The Ministry of Health proposed to introduce a law on “Cellular Biomedical Technologies,” which would establish an indefinite ban on human cloning. In the edition that was adopted and entered into force on January 1, 2017 , there is no word “cloning”, but there is a ban on the creation of a human embryo. So the struggle continues.
Another scandal related to cloning was the activity of the Korean biologist Hwang U Sok. He worked at the Seoul National University and was engaged in cloning of stem cells. Hwan published several articles, describing the successful results of his research. However, in 2006 he was convicted of a fake experiment and a violation of bioethics. The biologist was disgraced and dismissed from his job. However, later he was partially rehabilitated when he was able to show cloned animals, but his scientific reputation was completely ruined.
Although a lot of time has passed and the excitement around cloning has been quietly asleep, but many questions, both biological and humanitarian in this area, still remain relevant. But the development of cloning technology continues.
After Dolly, clones of many farm animals were obtained, which opens prospects for widespread use of cloning in livestock. This zootechnology makes it possible to quickly produce herds of highly productive animals. There are already commercial offers. For example, in South Korea, Sooam BRF is cloning service dogs in search of explosives or drugs. This is considered a promising area, since the sense of smell in dogs is highly dependent on genetics, and obtaining clones can reduce the dropout rate in training animals. Even our police got acquainted with the cloned service dogs , though not very successfully .
Also, this company makes decent clones for dead pets. Although a little embarrassed that the head of the company and its main specialist is the already mentioned Hwang U Sok, but he is not engaged in scientific work, but he owns the cloning technique well.
Another possible direction of cloning is the re-creation of extinct species of animals. No, we probably will not see Jurassic Park live, but it’s quite possible to look at a mammoth or a dronta, although there are problems on this way .
In general, as with any new technology, cloning has its drawbacks. In particular, due to the fact that this is a very laborious process, which has a fairly low yield. We have to create a lot of embryos, of which less than half live before birth. On the other hand, compared with the result of Dolly (1/277), the current 30% survival rate can already be considered a breakthrough.
Also cloning raises the issue of genetic diversity. We get highly productive individuals, but in general the population is genetically poorer, which can turn into trouble in the future, when it turns out that all clones are poorly adapted to the slightest change in conditions. However, no one interferes with the conduct of normal breeding work in parallel with cloning.
In general, it remains to be seen that the birth of Dolly had a strong impact on our lives. And although many problems are not solved yet, the very appearance of this technology has changed biology forever. And the future will show whether humanity can use cloning intelligently for its own purposes. But in any case, a small sheep will still be for us an example of a fantasy that has become a reality.