An unforeseen event that nearly upset plans and a revelation kept secret for seven months: 25 years after the cloning of Dolly the sheep

It was around 4:30 pm on Friday, July 5, 1996. The investigator Douglas mcgavin, the cell culture technique Angela Scott, the agricultural specialist John bracken and the embryologist Bill ritchie, all the scientists of Roslin Institute, they were reunited on a farm on the outskirts of the Scottish city of Edinburgh. There, they watched with attention and some anxiety the actions of a veterinarian who had been summoned urgently to witness the impending birth of a sheep. They feared that complications would arise during the birthing process that would endanger the animal and threaten the work they had been doing for many years.

A few minutes later, the four of them, along with other onlookers who approached the place, witnessed a milestone in science: that day, the team of scientists led by Ian Wilmut and Keith Campbell he had succeeded in cloning, from an adult cell, the first mammal in history.

This was something unthinkable until now, since the same had been done with tadpoles before, but no one had been able to clone an adult. The animal was named “Dolly” and, some time later, it became the most famous sheep that ever lived.. The event drew worldwide attention, to the point that just a week after the announcement, the Roslin Institute had already received 3,000 phone calls from around the world.

The cloning was kept strictly a secret, and the world didn’t learn of Dolly’s existence until seven months later. On February 22, 1997, scientists announced the surprising achievement in an article published in the journal Nature. There it was detailed that, as with the previous frog, they used the technique of nuclear transfer, first implemented in 1962 by developmental biologist John Gurdon.

In an interview with Infobae, the geneticist Jorge Dotto He explained that this method “involves extracting the nucleus, where the DNA is located, from an adult sheep cell. Then, this nucleus is transferred – by means of an electrical impulse – to an ovum from which its own nucleus has been removed, which would be an “empty” ovum. This “new” egg with its new nucleus behaves like a recently fertilized egg and develops into an embryo, which in turn is implanted in the uterus of another sheep to allow the pregnancy to develop and the birth. This case, that of Dolly, would be like an example of GPA”.

Dolly was conceived five months before her birth as part of a project between the Roslin Institute and PPL Therapeutics. On February 8, 1996, embryologists Karen Walker and Bill Ritchie performed enucleation and fusion in a small room at the end of Roslin’s lab that was used to store objects. Before a setback had occurred: the cells they were going to use had been contaminated. So they both had to fight for another nuclear donor.

“I remember running around, thinking ‘what are we going to put in this?’ Because the cells we were going to use weren’t there. The last thing you want to do is lose the eggs you have. At least we wanted to try something, ”Walker told the trade magazine. American scientist.

They thus obtained some ovine mammary epithelial cells, with which we sought to increase the expression of proteins in milk. These were samples from a 6-year-old adult specimen of the same species as Dolly, the Finn Dorset. They took the test even though expectations were low. It took 277 nuclear transfer attempts to obtain 29 embryos that were implanted into female carriers. Hopes remained low and the skeptical gaze remained in the following months, as most of the cloned embryos were aborted.

“In animal cloning, complications arise: for example, only 4% of clones develop on live fetuses, and there is a high percentage of fetal, perinatal and neonatal deaths. Many clones die within 24 hours of birth from pulmonary, cardiovascular, or weight gain. They can also develop abnormalities of the immune system, brain, gastrointestinal tract, or infections of the umbilical cord. And, if they manage to survive these complications, the risk of premature aging remains, ”explained Dotto.

In the end, only one of those 29 embryos thrived.

The arrival of Dolly in the world

Dolly’s name was originally 6LL3, but it was changed the same day she was born. It was John Bracken who suggested calling it that in reference to the American singer and actress Dolly Parton.. The researcher explained that he relates the concept of breast cell to the characteristic physique of the artist. Legend has it that sometime later someone reached out to Parton’s rep to comment on this, believing he could take it the wrong way. But the agent would have replied that “There is no bad publicity”. The version reached investigators’ ears, although none were able to corroborate it.

The day of the birth of the mammal, which weighed 6.6 kilograms, the experts also recalled that “He was a very viable lamb, he got up very quickly, probably in the first half hour”, which was a very good indication that the whole process had gone smoothly. At least until then. Is it over time, the animal developed various diseases that caused its death before the age of seven, while on average sheep live between 11 and 12 years.

Dolly had a normal life until early 2001, when arthritis, inflammation and joint stiffness have been found. Two years later, progressive lung disease was discovered, a type of disease that occurs in sheep of advanced age. This image has stimulated certain theories and studies which have concluded that clones have a premature aging and part of the scientific community has sown multiple questions about the health of the clones.

However, those who followed Dolly’s evolution assured that there was no relation between the pathologies suffered by the sheep with its origin. They argued, among other things, that The four descendants of Dolly – Debbie, Denise, Dianna and Daisy, were born in 2007- they aged normally and in good health, with no signs of metabolic disease and with only slight degeneration of the joints.

The truth is that due to the seriousness of her health, Dolly euthanized her. He died on February 14, 2003.

Cloning today

The creation of Dolly was a before and after for science. Since, “Several animals of different species have been cloned, such as pigs, deer, frogs, mice, lambs, monkeys and rabbits. Argentina became the ninth country to clone cattle when in 2002 a company cloned a Jersey calf from an embryonic cell. In addition, in the country the first cloned horse was born in 2010. It is of the Creole breed. In December 2013, the first cloned polo mare from Latin America was also born in Argentina, ”explained Dotto.

One of the recent cases in the country has been the work of experts from UBA-CONICET, the National University of Río Cuarto (UNRC) and the support of the Temaikén Foundation, which last year they managed to clone zebra embryos, in order to preserve the genetic material of this animal.

The work of Wilmut, Campbell and company has shown that the process of the nucleus of an adult cell retains the potential to generate a new individual. He has advanced years in medical research and raised hopes that he has found the key to creating cells and organs compatible with the immune system of every patient in need of replacement “parts”.

In April 2013, a group of researchers carried out clone the first embryonic stem cells from a skin cell of an adult human. They are the ones that give rise to the various tissues of the human body, such as the heart, liver, kidneys and nerves, which makes potentially useful for treating any type of disease.

“In the future, some researchers will try to search for adult cells in thousands of people in order to identify the type of composition compatible with the most donors. Something similar to what is done in the search for compatibility between people before an organ transplant, “warned the geneticist.

Also, on the other hand, the Dolly affair opened a debate on the ethical aspects of cloning. “The controversial issue is the cloning of human beings. Technically, it is possible to perform cloning of humans as has been done in other mammals with the nuclear transfer method. But the possibility of developing malformations in the embryo or fetus, and the serious ethical problems it generates, are strong arguments against such an attempt at genetic manipulation“remarked Dotto.

And he added, “Humans and animals are much more than a large strand of DNA that expresses itself. The spiritual and the emotional play a key role in the essence and that is why we are unique, whatever our genome ”.

For now, efforts are now mainly focused on trying to save species on the brink of extinction through genetic reproduction, as happens with the Caballo Przewalski: Last year, a team of North American scientists successfully reproduced a foal of this breed from Mongolia using DNA from a specimen that died 22 years ago.

Just as it led to research that led to the manufacture of human embryonic stem cells, Dolly’s legacy can save many of the nearly half a million species at risk across the planet.

After the death of the sheep, the Institute donated his body to the National Museum of Scotland in Edinburgh, where it has become one of the most popular attractions. His demeanor remains there alongside an interactive exhibit on the ethics of GM animal creation showcasing current research from Roslin experts.

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