Twenty-five years ago, in February 1997, the world discovered with amazement, on television, the images of the sheep Dolly, the first mammal conceived by reproductive cloning from an adult cell.

In the scientific community, the announcement has the effect of an explosion, some hailing "a revolution", others already alerting to the ethical risks of such a practice. 

In reality, the sheep "6ll3" by its scientific name, renamed Dolly in homage to the singer Dolly Parton, was born seven months earlier thanks to a team of scientists from the Roslin Institute, at the University of Edinburgh.

To create this clone, and therefore give life to a being without any fertilization, the scientists removed a mammary cell from an adult sheep before fusing it with the unfertilized egg of a second sheep from which the nucleus had been removed.

The embryo thus formed was then implanted in a surrogate ewe. 

"It was a small revolution because it made us change our way of thinking", explains to France 24 Pascale Chavatte-Palmer, director of research within the joint research unit of developmental and reproductive biology ( BREED) at INRAE ​​and specialist in animal cloning issues.

"Until then, we were convinced that a somatic cell, that is to say, which already has a function, like a mammary cell, could not go back. With Dolly, we realized that we could start them from scratch."

In the years that followed, cloning multiplied in laboratories.

At INRAE, Pascale Chavatte-Palmer participates in the birth of cloned cows, sheep, rabbits and even rats.

"Our main objective was to try to better understand the development of cells and especially how a nucleus could be reprogrammed", she continues. 

The trained veterinarian then remembers her great enthusiasm.

“We imagined so many applications, for agriculture, medicine, to save endangered species…”

A costly and random technique

Twenty-five years later, cloning techniques have improved and refined, but these great dreams have not come true.

"We quickly realized that it would be much more complicated than we thought," says the specialist. 

In addition to the always very high costs generated by cloning, the success rates remain very low, reaching 15% for cattle, 6% for pigs and barely 1% for primates, according to the veterinarian.

"And when it succeeds, there are often problems. Some embryos never come to term. For others, we regularly observe problems with the placenta, growth abnormalities..." Difficult, therefore, to consider large-scale democratization. 

Despite everything, the technique has managed to make a small place for itself in agri-food companies.

If, in the European Union, the legislation prohibits the cloning of animals for purposes of breeding and food but also the importation into the territory of products derived from them, in the United States, in Canada, in Argentina or China, a cloned animal can end up on consumers' plates.

“Overall, the idea is to clone the best animals, whose meat is the most expensive, and to combine it with genetic modification to improve yields,” explains Pascale Chavatte-Palmer.

But this is still limited.

"There are about 500 cattle cloned for food use in the United States each year," said the specialist. 

Bringing pets back to life

But it's not just farm animals that can be cloned.

Some have also seen it as the solution to bring their pet back to life.

In 2018, singer and actress Barbara Streisand announced that she had cloned her dog Samantha, for 50,000 dollars, and had recovered two dogs resembling her. 

Since 2006, the South Korean company, the Sooam Biotech Research Foundation, a pioneer in the field, has been offering wealthy customers the possibility of cloning their cat, their dog or even their horse.

According to The Guardian newspaper, 700 puppies were bred between 2006 and 2015.

"We are clearly on a niche business, like those who go into space for pleasure," says Pascale Chavatte-Palmer.

"Especially since the animals resulting from cloning are not totally identical! They have the same genetic heritage, but they do not have the same environment: they do not have the same mother, they are not born at the same time. They could therefore have completely different characters."

Faced with the risk of extinction of certain species, others are considering using cloning to try to save them, or even bring extinct species back to life.

In February 2021, American scientists announced that they had created a black-footed ferret using the DNA of an animal frozen since 1988. Again, Pascale Chavatte-Palmer is doubtful.

"It's not a viable solution," she said.

"To really preserve the species, it would be necessary to succeed in cloning several animals, with staggering costs".

Not to mention that if the habitat in which it lives is destroyed, cloned or not, it may not survive. 

From Dolly to IPS cells

When Dolly was born, some scientists also considered using cloning for therapeutic purposes, in particular to treat degenerative diseases.

Projects that quickly came up against ethical limits.

"Anything related to human cloning obviously poses ethical and moral problems, especially with the idea of ​​creating embryos", explains the scientist.

“Besides, at no time was there any question of working on human reproductive cloning,” she underlines.

From the birth of Dolly, the States multiplied the safeguards to avoid abuses.

Twenty countries, including France, signed a protocol prohibiting the cloning of human beings in 1997. In 2005, the United Nations followed suit, also prohibiting cloning for therapeutic purposes.

Therapeutic cloning was finally eclipsed by the discovery of induced pluripotent stem cells, known as IPS.

In 2006, the Japanese Shinya Yamanaka indeed showed that it was possible to reprogram a cell without going through an embryo.

In short, if we place a cell in the presence of particular factors (the Yamanaka cocktail), we can reprogram it into a quasi-embryonic cell, called IPS.

A simpler, faster and above all less complicated technique from an ethical point of view. 

"This discovery certainly could not have taken place without Dolly, but it has, in fact, made therapeutic cloning obsolete," says Pascale Chavatte-Palmer.

Today, these IPS cells are regularly used to test drugs, or in research in the fight against degenerative diseases such as Parkinson's. 

But for some time now, cloning "à la Dolly" has offered new perspectives in the medical field.

In line with the success of the first xenograft - the transplant of a pig's heart into a human - scientists are now working to clone and then breed genetically modified pigs to serve as heart donors for humans.

"The goal is to modify the pigs so that their organs are not rejected by the recipients."

In principle, the cells in culture are modified before introducing them into an oocyte and implanting them in a carrier pig, following the same technique as for Dolly. 

"Today, cloning has finally become a tool like any other for scientists, with the flaws that we know about it. We no longer do cloning to do cloning, it is still used for other purposes", concludes as well as Pascale Chavatte-Palmer. 

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