On this day in medical history: Dolly the Sheep is euthanized

For most people, everything they ever learned about clones they learned from Dolly the Sheep. The Finn-Dorsett sheep with three mothers was born on July 5, 1996, and was euthanized at the age of 6 on February 14, 2003.

While she was not the first cloned animal—that title goes to a sea urchin born in the late 1800s¹—she was the first cloned from an adult cell through the process of somatic cell nuclear transfer (SCNT).

At the time of her euthanization, Dolly was noted to have arthritis and had a form of lung cancer called ovine pulmonary adenocarcinoma, which is also known as jaagsiekte. It is a fairly common disease in sheep, particularly in those kept indoors. For security reasons, Dolly had to sleep inside.

The news of the day painted the cloning process itself as the root of Dolly’s health issues. Many speculated that cloning had given Dolly short telomeres, which protect the ends of chromosomes and can have an effect how cells age.

However, a 2004 study² noted that Dolly’s telomere length could be attributable to the age of the donor cells, and that she appeared physiologically and phenotypically normal for a sheep her age and breed.

A 2016 study took an even a closer look. They chose a cohort of 13 cloned sheep, including 4 sheep derived from the same cell line as Dolly.³ After musculoskeletal assessments, metabolic testing, and blood pressure measurements in the cloned sheep and the healthy controls, they found that the health of the SCNT-cloned animals was relatively similar to their normal sheep counterparts.

“Although the efficiency of SCNT has improved in recent years, its overall efficiency remains low, with embryonic and gestational losses compared to natural mating and assisted reproduction,” the authors wrote. “For those clones that survive beyond the perinatal period, however, the emerging consensus, supported by the current data, is that they are healthy and seem to age normally.”

They added: “We could find no evidence, therefore, of a detrimental long-term effect of cloning by SCNT on the health of aged offspring among our cohort.”

So why did the death of Dolly dent the public’s faith in cloning, as an article in the British Medical Journal suggests?⁴ Perhaps the fault lies with a combination of a relatively unknown science, a sensationalist media, and a fear that one cloned sheep would lead directly to an army of human clones.

Regardless, Dolly’s real medical history was recently revisited in an article published in Scientific Reports.⁵ The study analyzed Dolly, her naturally conceived offspring Bonnie, and two predecessor cloned sheep, Megan and Morag.

They found that radiographic osteoarthritis (rOA) was more severe and affected more joints in Bonnie and Megan, who were older than Dolly. Bonnie and Megan had rOA in the majority of their joints, while Dolly did not have evidence of the disease in her shoulder, carpal, or hock joints. Morag, a clone of Megan, had minimal rOA at the time of her death.

Much was made of Dolly’s diagnosis at such a young age, but by the time she was euthanized she had produced six lambs. Pregnancy, regardless of BMI, is a known risk factor of OA in sheep.

The authors concluded that Dolly, her offspring, and her cloned cohort have aged normally when compared with naturally bred sheep.

While clones do have their own health problems, such as a decreased likelihood of surviving to term and an increased reliance on oxygen and glucose supplementation after birth, they appear to be otherwise normal when they grow up.

Unless, of course, they grew up on the covers of newspapers, like poor, misunderstood Dolly.

References:

1. Hans Adolf Eduard Driesch (1867-1941). The Embryo Project Encyclopedia. https://embryo.asu.edu/pages/hans-adolf-eduard-driesch-1867-1941. Accessed 2/12/18.
2. Shiels PG, et al. Cloning. 1999;1(2):119-125. 
3. Sinclair KD, et al. Nat Commun. 2016;26;7:12359.
4. Dyer O. BMJ. 2002 Jan 12;324(7329):67. 
5. Corr SA, et al. Sci Rep. 2017;7:15685.