15 November 2022

Genetics and cloning

Cloning technologies edit animal genetics

Andrey Uglanov, "Arguments of the Week"

Is it possible to raise pigs that will have more meat than fat? Is a pig's donor heart suitable for a person? Why was there tasteless beef in the Soviet Union? How to preserve Yaroslavl, Kholmogorsky and Yakut breeds of cows? And is it necessary to save them if they are not in demand now? Is cloning good for preserving breeds? Does Malek know who his dad and mom are? Academician of the Russian Academy of Sciences, Director of the Federal Research Center for Animal Husbandry, tells Andrey Uglanov, editor-in-chief of Arguments of the Week, about all this and much more Natalia Zinovieva.

Pig Heart– I always thought that genetics works more in the field of crop production.

All these GMOs are from there. And your center deals with animals. I heard that once at your institute they created genetically modified pigs, which should have as little fat as possible, but more meat. Lev Konstantinovich Ernst, the father of Konstantin Ernst, who headed your institute, was just doing this.

– Now our organization is called "The Federal Research Center of Animal Husbandry named after Academician L.K. Ernst". And genetics is only one of the areas of our work. Although it is a priority. Our institute has a long tradition, academician Lev Konstantinovich Ernst stood at the origins of the development of genetic technologies, who is rightfully considered the founder of biotechnologies of farm animals in our country. One of the "pioneer" works that took place under his supervision in the 80s of the last century was the creation and research of transgenic pigs.

Genetic modifications were developing rapidly abroad at that time, and Academician Ernst, being the vice-president of VASHNIL, could not stay away. The aim of the work was to study transgenic pigs with the growth hormone gene. It was believed that such a modification could lead to a change in the ratio of fat to meat. The results showed that there were some changes in the pigs, but everything turned out to be not as rosy as it initially seemed. But those works have allowed us to integrate into the development of bioengineering technologies at a higher level today.

– The brave soldier Schweik from Yaroslav Hasek's book was the orderly of regimental chaplain Katz. When Katz got drunk, he said: "I ask you to respect a human being in me, a being equivalent to a pig." It was funny then. But after some fifty years it turned out that the chaplain Katz was very close to the truth. The pig turned out to be very similar to a human in many respects. We even have some organs that are interchangeable. Does your center deal with the issues of "pig" donation?

– The technology of obtaining pigs modified by growth factors is identical to the technology of obtaining pigs modified to obtain donor organs for human transplantation. These works are financially very expensive, and it is impossible to carry them out on the basis of one, even a leading institute. Abroad, one of the companies has already invested huge funds in the creation of genetically modified pigs - organ donors for transplantation. Our institute does not have such an opportunity yet. But the creation of such pigs is based on the same principles and techniques as in our case.

Veal tenderness– Against the background of the global food crisis, there is a lot of talk that the world lacks not only grain, but also meat.

We are doing well with pork, its value on store shelves is not growing, and even sometimes falls. A completely different picture with beef. There is meat, and not bad, but the price is quite high. Does your center work with cows and bulls?

– Academician Ernst was at the origins of large-scale breeding, when the decision on which animals to get offspring from is based on the analysis of a huge amount of information. It was then that a system was created that made it possible to create new breeds and select animals with improved economic and useful qualities. Today, this system continues to work and develop.

– In the Soviet Union there was a well-known Holstein breed of cows. Formally dairy, but they were also allowed for meat. As a result, the beef in our stores was tough and tasteless. Now a well-known company grows Black Angus cows for meat. The meat here is completely different in quality. But calves are brought from abroad for this. And where are our meat breeds?

– In the Soviet Union, a variety of breeds were created that were perfectly adapted to local conditions. It is very important to have your own breeds, obtained and bred in our region, adapted to our realities. They use our feeds more efficiently and extract more useful substances from them. Accordingly, a person tied to this area, who eats their meat, gets what he needs and is accustomed to. All over the world there is a tendency to replace the diversity of breeds with one or two. The same Holstein breed is bred in more than 160 countries. Such breeds are called cross-border. They are the most adapted to industrial technologies. After all, enterprises are focused not only on meeting demand, but also on making a profit. Such breeds are more profitable for them. The Aberdeen-Angus breed that you mentioned is also from this category. There's nothing wrong with that. But our domestic breeds must be preserved. For example, the Yaroslavl breed has been bred since the time of Ivan the Terrible along with our other breed – the Kholmogorskaya. They even provided the royal court with dairy products of excellent quality. But today they are not in demand. Or take the Yakut breed. There were more than a hundred thousand of them, and today there are about 600 left.

– These are cows that live in the open air in winter and sleep in the snow. Why were they taken out?

– Today everything is dictated by the economy. They are very unpretentious, but they do not give enough milk. The Yakut breed, though in a threatening, but not yet in the worst condition. There is a Tagil breed, which has only 100 heads left. The Red Gorbatov breed is resistant to leukemia, there are only 800 of them left from several tens of thousands in Soviet times. But these breeds have preserved a unique genetic set, which may not be in demand today, since we are focused on high-tech production. But what will happen tomorrow? And if you have to go back to your own resources?

– Yes, they will ban us from importing Aberdeen calves tomorrow - and that's it, Russia is left without beef.

– A reproduction and breeding system has already been created for Aberdeen Anguses in the country. We already have our own production, we no longer import calves. Our selection system is not inferior and even surpasses the foreign one. We cooperate with the company that breeds this breed, and within the framework of the agricultural development program, the institute is one of the co-executors.

– How many Anguses are there in the country?

– I do not know the exact figure, but it is estimated in hundreds of thousands of heads. And within the framework of the state program, it is planned to bring up to at least 400 thousand heads of improved livestock. This will be achieved by combining the efforts of the real sector of the economy with scientific organizations.

Chimera– Your institute, even under Academician Lev Ernst, was engaged in obtaining a chimera bull.

What kind of animal is this?

– This is a bull that was obtained by manipulations at the cell level by combining four different embryos from four different breeds. Such an animal was born in 1985. It was a time of rapid development of biotechnologies in the field of reproduction of farm animals. Animal cloning laboratories were created all over the world. Getting a chimera bull showed that we are on a level and are not lagging behind the development of science all over the world. The embedded technologies have been developed today in terms of cloning technology, which is now considered as the main platform for obtaining genetically edited animals.

The country's first cloned heifer, which is already two years old and which was obtained as part of the project of the Russian Foundation for Basic Research (RFBR), is now pregnant, and in December we expect her first offspring. Cloning is the main technological platform for genomic editing. We do not consider animals obtained in this way as animals for obtaining food. An increase in meat and dairy productivity can be achieved by traditional breeding methods. Gene in gene editing is the creation of technologies of the future. These animals can be used as organ donors, as protein suppliers for the pharmaceutical industry, or for other as yet undefined purposes. After all, we do not know what challenges we may face. Gene editing will help us to be ready even for unknown challenges.

– Can cloning help preserve traditional breeds like the Kholmogorskaya, which, as you say, are catastrophically few left?

– This may be a way to preserve the breed, but only "one of". Because cloning is still copying. This way we will get a large number of identical copies. From the point of view of preserving the breed, this is more bad than good. To preserve the breeds, we are working on other technologies – reproduction biotechnologies, which are based on obtaining embryos in vitro, or, as they often say, "in vitro". We take samples from typical animals of the breed. With the help of deep genomic analysis, we can identify the animal that has retained the largest share of ancestral genetic components.

We have a database of genotypes of animals that lived a hundred years ago. This became possible due to the fact that more than a hundred years ago, the founder of our institute, Academician Efim Fedotovich Liskun, created a collection of samples of cattle skulls of different breeds at the Timiryazev Academy. There are more than 300 of them. It is unlikely that he then thought that in a hundred years we will use them to obtain information about the genome of animals. But this allowed us to compare modern animals with their ancestors and find out which animal has preserved the signs of its ancestors to a greater extent. And we can get embryos from these animals and preserve the genetic resources of our breeds in the form of an embryo bank. These embryos can be planted to a cow of any breed at any time. The calf will be born of the breed that the embryo was. 200 embryos is a guarantee that the breed will not be lost.

Kungur– Besides the chick you were talking about, have you cloned anyone?

– We have a lamb named Kungur. This is not just a clone of a domestic sheep, but a clone of a hybrid of a Romanov breed domestic sheep and a wild Pamir sheep, argali. The Romanov sheep is our oldest breed. She is very prolific, there can be from three to five lambs in one litter. She is able to give offspring throughout the year, and not only in the spring, like most others. It is well adapted to breeding in Russian regions and has excellent maternal qualities. But the animal is not very large, there is not enough meat from it. Argali has qualities missing from the Romanov sheep – unpretentiousness, a strong backbone and a decent mass. We plan to edit this line further by turning off the myostatin gene, which slows down the build-up of muscle mass. As a result, we plan to get a clone that will combine the useful qualities of both Romanov sheep and argali, whose backbone will be able to carry additional muscle mass.

– I know that you are also engaged in fish breeding. Exotic!

– Genetic work with aquaculture is very important. Any selection is aimed at breeding the best samples. But there are difficulties with aquaculture in this regard. For breeding, a prerequisite is to know from which individuals the descendant was born. You need to know Dad and Mom. But in aquaculture it is impossible, there are other technologies. There they mix the eggs of different females and pour milk on different males.

It is not known from whom this or that malek originated. For commodity production, this does not play any role. But for breeding work, this is very important. That is why we have taken up the development of this direction in our center, where we will be able not only to track "fatherhood" and "motherhood", but also to choose the genetically best individuals.

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