How afraid of human cloning should we be? – Philip Ball. * Here’s why we’re still not cloning humans, 20 years after Dolly the sheep – Sharon Begley.

The creation of two monkeys brings the science of human cloning closer to reality. But that doesn’t mean it will happen.

Philip Ball

The cloning of macaque monkeys in China makes human reproductive cloning more conceivable. At the same time, it confirms how difficult it would be to clone a random adult – Adolf Hitler, say – from a piece of their tissue. And it changes nothing in the debate about whether such human cloning should ever happen.

Since the cloning of Dolly the sheep by scientists in Scotland in 1996, several other mammals have been cloned, including dogs, cats and pigs. But the same methods didn’t work so well for primates – like monkeys, and us. That’s why this latest step is significant. It shows that, with a bit of modification, the technique used for Dolly can create cloned, apparently healthy baby monkeys. The pair made this way by scientists at the Institute of Neuroscience in Shanghai have been christened Hua Hua and Zhong Zhong.

Crucially, the cute duo were cloned from the genetic material in cells of a macaque foetus, not from an adult monkey. This material – the chromosomes, housed in the cell’s nucleus – was extracted from the donor cell and placed inside the egg from an adult monkey, from which its own nucleus had first been removed. The egg was then stimulated to grow into an embryo in a surrogate mother’s womb, to make the egg respond as if it had been fertilised.

The important additional step – not needed for Dolly and her ilk – was to add some molecules to the egg before implantation that could activate genes involved in embryo development. Without that encouragement, these genes don’t seem to “awaken” in primates, and so the embryo can’t develop. But it seems that, in adult cells, those genes can’t so easily be revived, which is what still prevents the successful cloning of adult monkeys. In contrast, Dolly was cloned from cells of an adult ewe.

The Chinese scientists want to clone monkeys to study the genetic factors behind Alzheimer’s disease. With a strain of genetically identical monkeys, they can deactivate individual genes thought to play a role in the disease and see what effect it has. Such biomedical use of primates is fraught with ethical issues of its own – it is of course the very closeness of the relationship to humans that makes such research more informative but also more disturbing.

But the research also reopens the debate about human reproductive cloning. No one can yet know if cloning of a human foetus would work this way, but it seems entirely possible. Human cloning for reproduction is banned in many countries (including the UK), and a declaration by the UN in 2005 called on all states to prohibit it as “incompatible with human dignity and the protection of human life”. Right now there is every reason to respect that advice on safety grounds alone. Hua Hua and Zhong Zhong were the only live births from six pregnancies, resulting from the implantation of 79 cloned embryos into 21 surrogates. Two baby macaques were in fact born from embryos cloned from adult cells, but both died – one from impaired body development, the other from respiratory failure.

My guess is that the success rate will improve – and that there will eventually be successful cloning from adult cells. That won’t obviate safety concerns for human cloning though, and it’s hard to see quite how the issue can ever be convincingly resolved short of actually giving it a try. That was how IVF began. Many people, including some eminent scientists, were convinced that it would lead to birth defects. But in the absence of a clear ethical framework, Robert Edwards and Patrick Steptoe were able to try it anyway in 1977. Their bold, even reckless move has now alleviated the pain of infertility for millions of people.

It’s hard to make any comparable case for human reproductive cloning – to argue that the potential benefits create a risk worth taking. To construct a scenario where cloning seems a valid option for reproduction takes a lot of ingenuity: say, where a heterosexual couple want a biological child but one of them is sure to pass on some complex genetic disorder and they object to sperm or egg donation. Even in those cases, advances in other reproductive technologies such as gene editing or the production of sperm or egg cells from other body cells seem likely to render recourse to cloning futile.

It’s not hard to think up invalid reasons for human cloning, of course – most obviously, the vanity of imagining that one is somehow creating a “copy” of oneself and thereby prolonging one’s life. That notion would not only be obnoxious but deluded. Which is not to say that it would prevent someone from giving it a go. The fantasist “human cloning company” Clonaid, run by the Raëlian cult, which spuriously claimed to have created the first cloned child in 2002, stated (with no apparent irony) in its publicity material that “a surprisingly large number” of the requests it had received “come from the Los Angeles/Hollywood area”.

Yet although human reproductive cloning would be foolish and lacking solid motivation, that doesn’t excuse some of the baseless reasons often advanced against it. Suggestions that a cloned child would be stigmatised, “diminished”, “handmade”, “unnatural”, “soulless” and the start of a slippery slope to Brave New World, echo many of the earlier objections to IVF. The cloning debate reveals more about our prejudices towards reproductive technologies in general than it does about our ability to make wise decisions about biomedical advances. A good case was never made with bad arguments.

The Guardian

*

Here’s why we’re still not cloning humans, 20 years after Dolly the sheep

Sharon Begley

Dolly, the first animal to be cloned from an adult of its species, was born in 1996 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.

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