A Nobel Prize Well-Deserved

Two stem cell researchers have shared the Nobel Prize in Medicine for 2012, an elderly Briton, Sir John B. Gurdon, and a younger Japanese, Shinya Yamanaka. By a serendipitous coincidence, Sir John made his discovery in 1962 — the year of Yamanaka’s birth.

Fifty years of stem cell research have brought cures for intractable diseases within reach but they have also generated firestorms of controversy. Between 2001 and 2008, stem cell research vied with climate change as the most contentious issue in science. But since then, the firestorm died down — basically because of Yamanaka’s achievements. In fact, Tom Douglas, of the Uehiro Centre for Practical Ethics, at Oxford University, describes Yamanaka’s work as “a rare example of a scientific discovery that may solve more ethical problems than it creates”.

So what happened in these 50 years? (Click here for a graphic explanation from the Nobel Committee.)

In his classic experiment at the University of Cambridge, Sir John discovered that cell development is reversible. The conventional wisdom was that cells could never change once they had specialized as nerve, skin, or muscle cells. He proved that this was wrong by replacing the nucleus of a frog egg cell with a nucleus from a mature intestinal cell. This modified cell developed into a normal tadpole.

This astonishing development eventually led to the cloning of the first mammal, Dolly the sheep, in 1996 and subsequent attempts by rogue scientists to clone human beings.

But while the technique clearly worked, no one really understood how cell development worked. The obvious target for research was the embryo. From this ball of undifferentiated cells come each of the body’s specialized cells — more than 200 of them in humans. Surely the answer must lie there. In 1998 an American scientist, James Thomson, of the University of Wisconsin-Madison, isolated and cultivated human embryonic stem cells.

But a one-eyed focus on embryos left stem cell science hostage to ethics. Despite scientists’ bravado, everyone had some qualms about destroying embryos for their stem cells. Even Thomson admitted to the New York Times that “if human embryonic stem cell research does not make you at least a little bit uncomfortable, you have not thought about it enough”.

Still, it seemed the only way forward. Desperate patient advocates, backed by a supporting chorus of bioethicists, scientists and doctors, argued tearfully that the possibility of miracle cures had to trump ethics.

But, in 2006, there came astonishing news from the University of Kyoto. An orthopaedic surgeon turned stem cell scientist, Shinya Yamanaka, had discovered that skin cells from mature mice could be reprogrammed to become immature stem cells. It was an amazingly imaginative step. Instead of mimicking natural development from embryo to adult, why not wind back the clock from adult to embryo?

Yamanaka found that by introducing only a few genes, specialized skin cells could become pluripotent stem cells, i.e. immature cells that can develop into all types of cells in the body. Until then, creating pluripotent cells without resorting to cloning seemed unlikely. Like Gurdon, for whom he has an immense respect, Yamanaka had skittled the conventional wisdom.

This was electrifying news for biologists. It was as if commuters on the pot-holed, terrorist-infested road from Baghdad airport to the Green Zone could suddenly detour down a six-lane autobahn at 200km. Many famous scientists dropped human embryonic stem cells and began work on what Yamanaka had termed “induced pluripotent stem cells”. A year later, in November 2007, both he and James Thomson, in separate papers, confirmed that human cells could also be reprogrammed.

The rest is history.

As the Nobel Committee says about Gurdon and Yamanaka’s research, “Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.”

What turned Yamanaka away from the group-think which goaded his colleagues into the swamp of human embryonic stem cell research? Nowadays, the feverish excitement over human embryonic stem cells in the early Noughties seems ridiculous. Leading scientific and medical journals launched a crusade of Enlightenment heroes against prejudiced troglodytes. In one memorable endorsement of embryo research, the New England Journal of Medicine  — the world’s leading medical journal – published an editorial which concluded with this cringeworthy hyperbole: “The Promethean prospect of eternal regeneration awaits us, while time’s vulture looks on.” It never mentioned cell reprogramming.

Yamanaka’s originality may have sprung from his ethical sensitivities. Even Julian Savulescu, the director of the Oxford Uehiro Centre for Practical Ethics, who has no objections to embryo research, recognises this. “Yamanaka has taken people’s ethical concerns seriously about embryo research and modified the trajectory of research into a path that is acceptable for all. He deserves not only a Nobel Prize for Medicine, but a Nobel Prize for Ethics.”

In an interview with the New York Times in 2007, Yamanaka remembered one day years before when he paid a social visit to a friend’s IVF clinic. There, he peered through a microscope. “When I saw the embryo, I suddenly realised there was such a small difference between it and my daughters,” said the father of two. “I thought, we can’t keep destroying embryos for our research. There must be another way.”

Nor does he believe that scientists should put progress above ethics. In another 2007 interview, with New Scientist, he spoke about the firestorms. “These are very difficult decisions, and I think that society should make them,” he said. “It should not be scientists. They can find it difficult to think like the person on the street, and instead may see it simply as a good opportunity. We scientists can be involved in the decision-making process, but I think unless society is comfortable with the therapy it should not go ahead.”

Once again, experience shows that that ethical science is good science.

Michael Cook

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Michael Cook likes bad puns, bushwalking and black coffee. He did a BA at Harvard University in the US where it was good for networking, but moved to Sydney where it wasn’t. He also did a PhD on an obscure corner of Australian literature. He has worked as a book editor and magazine editor and has published articles in magazines and newspapers in the US, the UK and Australia.

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