Scientists have learned to clone people. What that means?

A group of scientists from the Chinese Academy of Sciences cloned for the first time macaques (Macaca fascicularis) in the same way that led to the birth of the Dolly sheep. This gave biologists the opportunity to clone primates, including humans. "" tells about a study published in the Cell journal.

There was never such a thing

Through the efforts of scientists, two females appeared - Zhong Zhong and Hua Hua. Both females are healthy and currently live in an incubator. The difference in age between them is one week, but both macaques are genetic identical copies: they were obtained from the same culture of fetal monkey cells.

In fact, these macaques are not the first cloned monkeys in the world. In 1999, researchers cloned rhesus monkeys by fragmenting the primate embryo into several parts, resulting in identical twins. In another work, cloned monkey cells were used to create stem cell lines. However, all this was done exclusively in Petri dishes, and the receipt of developed monkeys in the plans of scientists was not included.

Why is it that in 2018 cloned monkeys are considered a big breakthrough? The point is that for this purpose a technique called a somatic cell nucleus transplantation was used. In contrast to the fragmentation of the embryo, this method in theory makes it possible to obtain an unlimited number of clones from one donor. And what can be more convenient for biomedical research than a genetically homogeneous population of primates close to humans?

Since the time of the Dolly sheep, scientists have cloned 23 species of animals, including dogs, cats, rabbits, pigs and cows. However, the production of genetically identical primates means that, in principle, we can get human clones (although macaques do not refer to humanoid monkeys like gorillas or chimpanzees). However, scientists assured that they do not have the goal to clone people.

Benefits everywhere

Naturally, among people who are far from science and opponents of cloning, there may be suspicions that scientists have decided for a reason to re-encroach on the laws of nature - perhaps they consciously or accidentally create a biological weapon that will eventually destroy humanity. However, do not forget that the overall mortality rate of people, including all sorts of opponents of biotechnology (from anti-vaccination to GMO-fobs) at the end of the 20th and beginning of the 21st century has greatly decreased precisely thanks to the achievements of biology and medicine. Although many are unreasonably afraid of cloning, this method will give scientists unprecedented opportunities to create new drugs.

First of all, we are talking about the creation of convenient model organisms. Macaques are used for research in the field of medicine, neurobiology and behavior. Their genome is 93 percent identical to the human one (our common ancestor lived 25 million years ago), and the differences are largely due to genomic rearrangements, rather than to individual mutations. In other words, the human genome is a kind of an anagram of the macaque genome. At the same time, those variants of genes that are normal in macaques can cause diseases in humans - for example, phenylketonuria.

Cloning allows obtaining clean lines, that is, groups of genetically homogeneous organisms. This can be achieved through crossing, but for monkeys with their relatively long maturation period, this method is impractical. Clones are very convenient for testing drugs. Imagine that you have dozens of primates, and you randomly divide them into two groups. Animals in one group you give medicine, and in the other - a pacifier. It would seem that if the drug is effective, then the health of primates in the first group should improve. But in fact, the result may be masked by genetic differences. Thus, some animals may be immune to the drug or, conversely, be too sensitive, which will cause their death. For reliable results, large groups of animals have to be used, which is difficult and expensive, however, clean lines solve this problem.

Often, animal models in medical research are genetically prone to developing diseases similar to human: cancer, various types of dementia, Parkinson's disease, hereditary disorders or autism. They are experiencing new therapeutic methods. Cloning will allow researchers to be sure that all animals in the group because of their identity will precisely develop this or that disease.

She's not Dolly

Cloning by the method of the somatic cell nucleus transplantation is carried out as follows. From the unfertilized oocyte, the nucleus is removed, after which the nucleus is transplanted from the somatic cell, for example, from the fibroblast (connective tissue cells) of the embryo. The method was developed in 1996, when the Scottish biologists under the leadership of Jan Vilmut were able to clone the Dolly sheep. Epithelial cells of the mammary gland were used as nuclear donors. However, not all the ovules to which the nucleus was transplanted survived. It took about three hundred attempts to get a healthy embryo.

The difficulty of cloning monkeys is that for each species, protocols for the chemical processing of DNA from the donor nucleus should be developed in order to "rejuvenate" it. Early attempts to transplant the nucleus in primates ended in failure precisely because of improper reprogramming of donor cells. However, later it turned out that the efficiency of transplantation can be increased with the help of a number of chemical substances that block the activity of histone deacetylase enzymes. In addition, regions of DNA that were resistant to reprogramming were identified - they showed a high level of methyl groups that inhibited gene activation.

As easy as pie

In order to understand what exactly scientists have done, it is necessary to know only the very foundations of epigenetics. Histones are the proteins of various types, combining into a globule (nucleosome), around which a part of the DNA is wound around 1.67 turns. On one strand of DNA is a large number of nucleosomes, affecting the packing density of genetic material and gene activity. They do this with the help of four tails protruding from two histones H3 and two histones H4. To different parts of these tails can be joined both methyl (methylation) and acetyl (acetylation) groups.

There are a great many types of methylation of histones, in which from one to three methyl groups are added to different parts of the tail. In methylation, designated as H3K9me3, three groups (me3) attach to the ninth with the end amino acid being lysine (K) located at the tail of histone H3. On a DNA site enriched with H3K9me3, genes are usually blocked. Acetylation occurs in a similar way, however, on the contrary, it promotes the activation of genes.

Acetylation and methylation are necessary for the differentiation of cells, when stem embryonic cells choose their "professions". In this case, some genes are switched on and others are turned off. It turned out that H3K9me3 protects genes that are not needed by fibroblast, from re-activation, which is the main obstacle to reprogramming. To solve this problem, scientists used trichostatin A, which promoted histone acetylation, and also introduced into the eggs with the nucleus already transplanted the RNA molecule that codes for histone demethylase, an enzyme that cleans methyl groups from histones.

A total of 127 eggs were used. Scientists managed to get 109 embryos, but only 79 of them were transplanted into the uterus of 21 female crab-eating macaques. Pregnancy was confirmed only in four animals, but only two monkeys gave birth to healthy cubs.

Do not panic

When it comes to new opportunities for biotechnology, those who see it as nothing more than an attack on ethical standards come to the scene. Organizations that advocate for animals generally consider animal experiments (especially those similar to humans) unacceptable - apparently forgetting the fact that it was thanks to animals that mankind defeated dangerous infectious diseases, including smallpox, which killed millions of people. Many breakthroughs in the field of medicine would not have happened without the use of animal models.

Some scientists, for example, neuroscientists and ethologists, believe that animals can be replaced to some extent with computer models, but so far there are no technologies to simulate the whole organism and the effect of drugs on it. Even tissue cultures (or grown in-tube organs) can not replace an animal, because reacting to drugs these objects will be completely different. So the question, whether it is necessary to conduct experiments on living beings for the development of medicine, requires, perhaps, an uncomfortable but honest answer: now these experiments are necessary.

Do we need to be afraid of cloning people? The ability to make genetically identical copies of people will appear in a few years, although it is worthwhile to think about why this is done? It is very difficult to take an adult's DNA and make a copy of him in the form of an infant - without perfecting the technique of reprogramming somatic cells, all biological material from the donor will go into the trash. Spending money on copies of the same human embryos is simply not practical. And to clone Hitler, Jesus Christ or the dinosaur, from which there are no cells with nuclei, it is possible only in the genre of fiction.

Arthur Swan
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