Dolly, the first animal to be cloned from an adult of its species, was born 20 years ago today at the Roslin Institute in Scotland. When her creators announced what they had done, it triggered warnings of rich people cloning themselves for spare parts, of tyrants cloning soldiers for armies, of bereaved parents cloning their dead child to produce a replacement — and promises that the technique would bring medical breakthroughs. Which raises some questions:
Why are there no human clones?
Because of scientific, ethical, and commercial reasons.
The scientists who created Dolly — named after Dolly Parton, naturally — removed the DNA from a sheep ovum, fused the ovum with a mammary epithelial cell from an adult “donor” sheep, and transplanted the result, now carrying DNA only from the donor, into a surrogate ewe. But that technique, called somatic cell nuclear transfer (SCNT), turned out not to be so easy in other species.
“I think no one realized how hard cloning would be in some species though relatively easy in others,” said legal scholar and bioethicist Hank Greely of Stanford University. “Cats: easy; dogs: hard; mice: easy; rats: hard; humans and other primates: very hard.”
There has also been no commercial motive for human cloning. Both the assisted reproduction (IVF) and pharmaceutical industries “immediately said they had no interest in human cloning,” said bioethicist George Annas of Boston University. “That was a big deal. All new technologies are driven by the profit motive,” absent which they tend to languish.
The Raelians (a cult that believes humans are the clones of aliens) claimed in 2002 that they had cloned a baby from a 31-year-old American woman, but for some reason the now 13-year-old “Eve” has never stepped forward to claim her place in history.
But surely someone has made money from Dolly-like cloning work?
Livestock cloning has become a commercial business, with ViaGen — part of biotech company Intrexon — cloning cattle, sheep, and pigs. It also clones pets. But it’s not a huge business.
In South Korea, biologist Woo Suk Hwang rebounded from scandal (in 2004, he fraudulently claimed to have cloned a human embryo) to clone hundreds of dogs, cows, pigs, and even coyotes. Price for Fido Redux: about $100,000, Nature reported.
While pet cloning “remains very expensive and very uncommon,” said Greely, “the world’s best polo pony team is made up of clones.” The thoroughbred racing industry bans clones, however.
Did Dolly start a revolution?
If you count by scientific publications, sure: There were only about 60 papers on somatic cell nuclear transfer in the decade before her birth, most of them describing (failed) attempts to use it to produce prized cattle and other commercial livestock, and 5,870 in the decade after, many of them reporting progress toward medical uses of SCNT.
Where are those medical breakthroughs?
They were premised on what’s called therapeutic cloning, to distinguish it from reproductive cloning. The idea is to take a cell from a patient, put its DNA into an ovum whose own DNA was removed, and get the ovum to begin dividing and multiplying in a lab dish, eventually producing specialized cells like neurons and pancreatic beta cells. Those cells could be used for basic research, such as to follow how a disease like ALS develops at the cellular level, or for therapy.
In 2013, a team led by reproductive biologist Shoukhrat Mitalipov of Oregon Health & Science University used somatic cell nuclear transfer to create a human cell line. There hasn’t been enough time since then for the rest of the therapeutic cloning promise to be realized.
2013? Why did it take so long?
Some animals turned out to be much harder to clone than others, and humans are really tough. It wasn’t until 2014 that scientists, led by Dieter Egli of the New York Stem Cell Foundation, used a variation on the Dolly recipe to create the first disease-specific cell lines from a patient, with type 1 diabetes. The donor’s DNA plus a DNA-free egg produced a line of cells Egli is using to grow insulin-producing beta cells that match the donor precisely, minimizing the chance of rejection. “Now you have cells that are genetically identical to the donor, which will allow us to make patient-specific cells for transplant,” Egli said. “We’re three-quarters of the way there, and that breakthrough is due to Dolly.”
So Dolly deserves the credit if such cells start to be used to cure diabetes and other diseases?
Sort of. Competing techniques, especially “reprogramming” adult cells so they can turn into (potentially) diabetes-curing beta cells and others, have diminished interest in SCNT, since it’s so much harder to pull off. But it was Dolly who showed not only that mammalian cloning can work, but also that “there is something in the egg that could take an adult cell [the sheep mammary cell] backwards in time and restore it to an embryonic state” able to become a whole new creature, said Dr. Robert Lanza, chief scientific officer of the Astellas Institute for Regenerative Medicine. “This is what spurred the discovery of iPS [induced pluripotent stem] cells,” the reprogrammed adult cells that might finally make stem-cell medicine a reality.
Did Dolly have effects outside medicine?
Yes, for endangered species. Lanza and his team adapted the Dolly-making technique to clone endangered species. The first, a gaur, was born in 2001, and their banteng (a species of wild ox) was born in 2003. Both died within days, but efforts are underway to clone such endangered species as the black-footed ferret, possibly the northern white rhino, giant pandas,— and also extinct animals such as the passenger pigeon and mammoth, Lanza said: “We’re likely to see de-extinction become a reality in our lifetime.”
Where is Dolly now?
After developing a lung disease called jaagsiekte, she was euthanized on Feb. 14, 2003, stuffed, and put on display at the Museum of Scotland in Edinburgh, where you can find her in a new science gallery starting on Friday.