“This is a tool that can not be used everywhere”: a biologist about animal cloning in Russia and in the world

How did scientists come up with the idea of ​​cloning?

- The first study that formed the basis of work on cloning - obtaining identical individuals - was the experience of the German embryologist Hans Spemann, in which he demonstrated that at the 16-cell stage, salamander eggs have pluripotent properties, that is, they can turn into different types of tissue.

Cloning in general is the copying of the genetic material of an individual.

This can be done by taking the nucleus of an embryo or a somatic cell as a source.

In the first case, when the embryo develops at an early stage, up to 16 cells, it can be divided into 16 identical sources of nuclei.

The first experiment on embryonic cloning of mammals took place in 1981 on mice.

And in 1986, the same experiment was carried out with a sheep.

But the famous sheep Dolly appeared in 1996 as a result of cloning, for which not an embryonic, but a somatic cell was used.

It was from this that a new stage in science began.

- Why is it so important that cloning was carried out using a somatic cell?

- Embryonic cloning is limited by the number of nuclei in the embryo: its division is only possible up to a certain stage.

So, you limit yourself to the number of clones you can get.

Plus, you don't know who you end up cloning.

In somatic cloning, when it comes to an adult animal, you use tissue from the originally known genome.

And the number of clones is virtually unlimited.

Potentially, you can get a fairly large number of cells from an animal, freeze them and store them for a long time.

During embryonic cloning, nuclei cannot be frozen.

Nuclear cloning was a stepping stone to somatic cloning.

It was believed that only the cells of the embryo are able to give further development to the offspring.

Until Dolly the Sheep was born, it never occurred to anyone that a somatic cell, once inside an egg, could be reprogrammed.  

- How long ago did cloning experiments begin in Russia?

— At our institute — since 2006.

This was within the framework of experiments to obtain embryos. 

— Your laboratory is engaged in the study of cloning for animal husbandry.

Why do you need to go in such a difficult way, if nature has everything worked out?

- If we are talking about animal husbandry, then one of these areas is the cloning of unique individuals.

For example, if you take a bull, he is measured by daughters, and usually five or six years pass from the moment when data begins to accumulate on his performance and whether his offspring have increased milk production.

This allows you to understand whether it is an improver or not.

Nobody canceled the usual selection, but if in the end we find out that we got a unique highly productive bull, cloning such an animal is definitely advisable: it will take much longer to breed it than to clone it.

This practice has long been used abroad, there are commercial organizations that are engaged in this.

So far, we are only undergoing the first experiments, it is too early to talk about scaling.

Our team is currently focusing on genomic editing. 

• Galina Singina – Head of the Laboratory of Experimental Embryology, FRC VIZh named after A.I.

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“The cloning technique we talked about is the basis for genome editing.

Could you tell us about the essence of this method?

— Most often, we use somatic cells (fetal fibroblasts) for cloning, which are initially modified in the direction of a knockout of a gene using the CRISPR/Cas system.

For example, we are currently conducting a study in which the gene for beta-lactoglobulin is edited in cows.

His knockout leads to the production of milk with low allergenic properties.

The same experiments are carried out with respect to the myostatin gene, the knockout of which leads to an increase in the muscle mass of the animal. 

— Can we say that cloning and genome editing will fundamentally change the approach to animal breeding, will accelerate this process?

- Certainly.

We can breed for years, cross something so that some gene disappears, but, as a rule, this does not work out.

If we want, for example, to achieve an increase in mass by conventional selection, then it means that individuals with the appropriate characteristics must be selected, which can take decades.

Whereas editing in combination with the cloning method allows you to achieve results within one individual.

— How is the selection of the gene to be edited carried out? 

- First of all, it is necessary to understand which gene is responsible for what.

At the same time, the choice is not that big: at the moment, scientists do not know very many target genes that can be worked with, removed or replaced.

In practice, these genes can be counted on the fingers.

So far, the tools for genomic editing are also limited.

So almost the entire scientific world community is now searching for target genes that could provide the desired advantage of the animal.

— What are the most pressing needs of livestock breeders now?

“The main work is going on in three areas: increasing productivity, improving the technological parameters of products and resistance to diseases.

The main thing in animal husbandry is an economically useful sign.

Thus, milk with low allergenic properties will allow it to occupy a certain sector in sales, for example, in this case it is baby food.

Various growth hormones were once used for mass growth, but genomic editing for this purpose is safer. 

• Cloned cow Flower.

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— A successful experiment on cow cloning has been carried out at your institute.

When it was born, how was it carried out and what is the scientific value of this experience?

“This experiment, obtaining live offspring, was the final step in confirming that we have the technology of cloning. 

Cow Flower became the first cloned animal in Russia.

Our laboratory came to somatic cloning in an evolutionary way.

And we are the only ones in the post-Soviet space who conduct such experiments. 

- What problems have to be solved?

- When performing such tasks, problems, of course, arise, but now, when the work is completed, you no longer remember them and set yourself new ones.

That is why, despite the lockdown, we very quickly got a clone of another animal species - a hybrid of sheep and argali.

Things will only get better from there.

These studies will be the first step towards genomic editing of the sheep. 

What terms do you use for parents of cloned animals? 

Our cow Flower is a clone.

Each clone has a donor of genetic material, that is, a source of a somatic cell.

And there is an intermediate animal that has to bear the cloned embryo.

In medicine, it would be called a surrogate mother, we use the term "recipient animal".

• One of the stages of cloning in the laboratory of experimental embryology of the FRC VIZh named after

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- In the laboratory, we observed one of the stages of cloning, when the contents of the nucleus were replaced with clone material.

Could you elaborate on this?  

Cloning is a multi-step procedure.

The meaning of cloning is reprogramming: the somatic cell of the animal is placed in the egg, where it must actually "forget" that it was already an adult cell.

Also, “sleeping” genes that are in any somatic cell should wake up in it.

They just start the embryonic development of an enucleated egg, that is, “liberated” from its own (originally present) genetic material.

- On December 30, 2022, a calf was born at the Flower.

Offspring from a clone - how important is this for scientists?

— The history of cattle cloning has quite a long history.

The cow was cloned in 1998, that is, 25 years ago, however, as practice shows, a cloned animal is not always capable of reproduction.

The birth of the Flower was a joyful event.

But that wasn't enough.

It was necessary to understand how complete our animal is in terms of reproduction.

From a cloned bull, offspring should be obtained, from a cloned cow, too, because she must give milk.

This is also important if we want the animal to give milk with low allergenic properties. 

• The cloned cow Flower and her offspring - the calf Decembrist.

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Now the Decembrist calf has been born, the Flower gives milk, and we can talk about the continuation of work.

Our system has developed into a chain and it works: from the moment of receiving the embryo and its transplantation to the recipient animal, to postnatal development, childbirth, the birth of a clone, as well as its growth, maturation and ability to reproduce.

That is, our technology is basically working.

It is very important.

— Are there cloning technologies in nature?

- Natural natural cloning - the birth of identical twins, if we are talking about mammals. 

- In science fiction films, there is often a plot when scientists clone ancient lizards or a dead person.

It's real?

— I am not a science fiction writer and I can only talk about the results of the work that is currently available.

Cloning requires living tissue from which somatic cells are to be obtained.

But it's not just about the fabric.

It is also necessary to understand which animal can be used as an egg donor and as a recipient. 

In the case of cloning an animal of the wild fauna, the problem arises that there is no object - an intermediate animal, far from all individuals are suitable for this.

Basically, too many factors.

Cloning is a tool that humanity has, but so far it can not be used everywhere.

Scientists are trying to clone the mammoth, but nothing works because there is no living tissue - at the moment, cloning involves the use of only living somatic cells.

Nails and hair are not the best material for cloning.

In general, it has been shown that almost all types of tissue can potentially be used for this.

But whether living offspring will be born in each individual case and whether it will be capable of reproduction is a question.