20 Years after Dolly the Sheep Led the WayWhere Is Cloning Now?

It was a glorious day in the hills above Edinburgh, Scotland, when old friends and scientific colleagues Ian Wilmut and Alan Trounson set off on a hike two decades ago. High over the city, Wilmut confided that he had a secret to share. As part of a larger study, he and several co-workers had successfully birthed a lamb in the labnot from egg and sperm but from DNA taken from an adult sheeps mammary gland. They had cloned a mammal. Crikey, I was stunned, says Trounson, who is nowas thena stem cell biologist at Monash University in Melbourne, Australia. He remembers sitting down hard on a nearby stone. It was a warm day but Trounson felt a chill pass over him as he realized the implications. It changed everything.

Cloning a mammal defied the scientific dogma of its time. The success led to dire and fantastic predictions: Humans would be cloned. Diseases would be prevented. Lost children rebirthed. Today, two decades after Dollys birth on July 5, 1996, the impact of cloning on basic science has surpassed expectations whereas the reality of what is technically called nuclear transferthe form of cloning used with Dollyhas largely faded from public consciousness.

In 2016 cloning a person remains unfeasible, with no scientific benefit and an unacceptable level of risk, several scientists say. Most know of no one even considering the feat. And the cloning of animals remains limitedalthough it is likely growing. Some agricultural cloning is used in the U.S. and China to capitalize on the genes of a few extraordinary specimens, scientists say, but the European Parliament voted last year to ban cloning animals for food. One scientist in South Korea charges $100,000 to clone pets, although the level of demand for the service is unclear.

Clonings biggest impact, several researchers say, has been in the stem cell advances it has sparked. Stem cell biologist Shinya Yamanaka said via e-mail that Dollys cloning motivated him to begin developing stem cells derived from adult cellsan accomplishment that won him a Nobel Prize in 2012. Dolly the Sheep told me that nuclear reprogramming is possible even in mammalian cells and encouraged me to start my own project, wrote Yamanaka, who splits his time between the University of California, San Francisco, and the Center for iPS Cell Research and Application (CiRA) at Kyoto University in Japan, which he directs. He used adult cellsfirst in mice, although the technique is now feasible in human cellsto make stem cells that can form a wide range of other cells, essentially turning their cellular clocks back to infancy so they could mature into different adults. Because they are artificially created and can have a variety of futures, they are called induced pluripotent stem (or iPS) cells. The rise of these iPS cells has reduced the need for embryonic stem cellswhich have long caused ethical concerns for someand iPS cells now form the basis for most of todays stem cell research.

Dollys birth was transformative because it proved that the nucleus of the adult cell had all the DNA necessary to give rise to another animal, says stem cell biologist Robin Lovell-Badge, head of the Division of Stem Cell Biology and Developmental Genetics at the Francis Crick Institute in London. Previous researchers had derived adult frogs from embryonic frog cells or embryonic frog cells from adultsat which point their development stalled. Dolly was the first example of taking an adult cell and getting an adult, Lovell-Badge says. That meant you could reprogram an adult cell nucleus back to an embryonic stage.

Dolly died on February 14, 2003, at age six from a lung infection common among animals who are not given access to the outdoors. It probably had nothing to do with her being a cloned animal, says Wilmut, now an emeritus professor at the The Roslin Institute at the University of Edinburgh where he did his initial work.

The sheep, made from breast cells, was famously named after Dolly Parton, the American singer known for her large chest as well as her voice. It wasnt meant to be disrespectful to the lady in question or to women in general, Wilmut said recently, of the name suggested by a stockman. Rather, it helped humanize a research project that might otherwise have seemed detached from everyday life. Science and its presentation can sometimes look terribly serious, he said. I think it was good for usit made us look human.

Wilmut admits Dollys birth was a lucky accident. He and his colleagues were trying to make clones from fetal cells and used adult ones as experimental controlsnot expecting that they would actually generate an embryo of their own. We didnt set out to clone adult cells. We set out to work withideallyembryonic stem cells or things like that, Wilmut says. Being successful with adult cells was a very considerable, unexpected bonus.

The initial aim of the research was to use an animals milk production system as a factory of sorts, manufacturing proteins to treat human diseases. But interest in that idea has declined with the rise of inexpensive synthetic chemicals.

Wilmut says he thinks it would be possible to clone a humanbut highly unadvisable. The cloning technique used to create Dolly has been shown not to work in primates. He believes it could be possible using other techniques but said he is vehemently opposed to the idea of cloning a person. Just because it may now work in the sense of producing offspring doesnt mean to say we should do it, he says. The likelihood is you would get pregnancy losses, abnormal births. For example, one of the lambs his lab cloned soon after Dolly developed lung problems that caused it to hyperventilate and regularly pass out. It was distressing enough to see that in an animal, he says. I wouldnt want to be the person who looked a cloned child in the face and said very sorry. With recent advances in gene-editing technology, the need for cloning to correct genetic errors will decline even further, he notes. Theres even less reason for doing it now than before..

Trounson says he believes there is a large market for cloned livestock embryos. Its pretty busy out there, kind of surprisingly and below the surface, he says. The benefits genomically for production excellence and driving up production parameters is very good, adds Trounson, who recently stepped down after six years as president of the California Institute for Regenerative Medicine, a state agency that provides loans and grants for stem cell research. Thats probably the driver that has kept companies doing it in the U.S.

The U.S. government decided in 2008 that there were no discernable differences between cloned and noncloned cows, goats and pigs, so it allowed the process in those animals, although mainly for breeding rather than meat production. In China a company called Boyalife Group has plans to produce at least 100,0000 cloned beef cattlea fraction of the total number of animals slaughtered each year in that country, a company spokesperson wrote via e-mail. We might be at the best time to advance this technology into applications from both a technology perspective and from a market perspective [in China].

Theoretically, cloning could also be used to bring back endangered species. There has been talk of using it to restore woolly mammoths, giant pandas and even Neandertalsideas Lovell-Badge dismisses as fairly silly. Trounson says he still has a stash of skin samples from critically endangered northern hairy-nosed wombats stored in liquid nitrogen, in case someone ever wants to attempt to restore the speciess numbers. Clones, however, are created by taking an adult cell and fusing it to a recipient egg cell. Making a clone requires an intact nucleus, which would not be available for most extinct species.

Several researchers are now using cloning techniques to produce embryonic stem cells, thereby avoiding the need to collect new embryos. So-called somatic cell nuclear transfer may help researchers better understand early human embryogenesis and stem cell biology, according to Paul Knoepfler, a biologist at the University of California, Davis, who is not directly involved in the work. Knoepfler wrote via e-mail that he does not see any imminent therapeutic benefit [to that work], but that could change in the future.

The idea of cloning a deceased loved onehuman or pethas fallen out of favor in part because of the recognition that environment affects behavior. The genetics might be the same but would a clone still be the same lovable individual? Youre never going to get Tibble back, or whatever, Lovell-Badge says, noting that he thinks the idea of cloning a pet is stupid. He adds, The only possible use that I can sort of vaguely think of is if you have a particular valuable dog, with skills like super-sniffing that scientists would want to determine was inborn or behavioral.

Lovell-Badge is even more dismissive of the idea of cloning a person. Wed have to know an awful lot more about reprogramming and how to make it 100 percent efficient, he says. I have never thought of a good enough reason for a human being.

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20 Years after Dolly the Sheep Led the WayWhere Is Cloning Now?