Send in the clones

At 80, Nobel Laureate Sir John Gurdon still harbours ambitions of breaking ground in the controversial field of genetics research By Michael Ruffles

There may be no sweeter revenge for receiving a terrible school report than winning a Nobel Prize, even if it does come more than six decades later. But the most Sir John Gurdon, a gentleman to a fault at 80 and immaculately dressed shortly after landing in Bangkok from Hong Kong, allows himself is a polite if ironic chuckle.

Only one part of the report card he received as a 15 year old, when he was ranked last of 250 boys at Eton in biology, rings true today: that he “will insist on doing his work in his own way”. Sir John has spent most of his life challenging assumptions and questioning evidence while helping pioneer research in the often controversial field of genetic and cellular cloning that may soon lead to replacement tissue and body parts being available.
“That was, you could say, some kind of perception by the schoolmaster, but I don’t think he meant it in a positive way,” he said. “It was a very bad criticism of not listening to what he was saying. Much of what he was saying was probably wrong, in fact. I think it has been my custom to always question anything I’m told.”

Sir John was in Bangkok last week for the latest in a series of public lectures and workshops at Shinawatra University involving world-leading personalities and academics. Among the career highlights he spoke of were proving all cells in an organism contained the same genetic material; cloning a frog more than 30 years before Dolly the sheep came into being; and winning the 2012 Nobel Prize in Physiology and Medicine, for the discovery adult cells could be converted to the same state as embryonic stem cells. His career has been building towards “being able to reprogramme a cell so that you can provide new cells for patients when some of their tissues or body parts wear out and are no longer functioning”.

He also wanted to impart inspiration. “I had a very unpromising start to my education,” Sir John explained. “At the age of 15 I was given my first semester of science and I came in the bottom place of 250. So I was told no more science for me. I was required to study ancient Greek, Latin and a modern language, but before I went to university I was able to transfer to science, with great help from my parents and was admitted to Oxford to study zoology. From then onwards my career progressed into science.”

His first great breakthrough came while at Oxford, replacing the nucleus of a fertilised frog egg cell with one from a tadpole’s intestine cell.

“The work I was able to do did indeed, I think, provide the first definitive evidence that every cell in the body has the same set of genes,” Sir John said. “If this were not the case it would be impossible to do these cell replacement kinds of experiments and work that now attracts great interest. At the time this work was done, in the 1950s, this concept that every cell in the body has the same genes was not accepted at all, there was no evidence for it. At first there was considerable doubt whether these experiments I was involved in were sufficiently certain and safe to justify this conclusion.”

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As time has gone on and the benefits become more apparent, the field has become more accepted. Sir John likened the ethical criticisms that have been raised against cloning to the controversy that once surrounded in vitro fertilisation.

“The interesting thing is that, as soon as Bob Edwards had a success with IVF, the ethicists disappeared.

“I object to the hardline views of some Roman Catholics who say that human embryonic stem cells should not be used. But most people don’t share that view.”

In the UK, “ethical permission” is required before experimenting with embryonic cells and it’s possible to obtain this “if you have a sensible question”.

“If you just say ‘I like playing around with embryos’ they would say no, but if you have something that would be useful you can get permission to do it. There’s very few people who I come across who think that work on human embryos is ethically wrong. The potential good is so obvious.”

The practical benefits of cloning techniques are closer than most people know. Sir John’s work proving adult cells can be rejuvenated,and his next challenge to find out precisely how this happens, means that tissue, such as skin, could be turned into replacement body parts.

“In my view the most likely advance in the near future will be to provide replacement parts of the eye, starting from a piece of skin.Those who have poor vision or have even lost their vision may be able to recover some degree of ability to see. This is obviously a very desirable, practical benefit. I myself do not work on the eye, but the work we have been able to do provides a background for these advances.”

Sir John said there was almost no risk to the procedure although it might not work in all cases “it’s never going to be harmful”. However, scientists were facing resistance from regulatory bodies he criticised as overly conservative.

“The regulatory bodies are holding things back quite badly, in my view, requiring more and more tests and delaying the availability of this work to the public.

“They would say that one person suffering is more important than 100,000 people benefiting, and those numbers don’t work out in my opinion. What they’re really doing is holding back the benefit that thousands could have, so it’s obviously, in my view, a completely harmful procedure. I would love to see these regulatory bodies replaced.”

The possibilities for genetic and cellular cloning seem to stretch into the realm of science-fiction, but Sir John acknowledged there were likely to be limits to what could be accomplished.

“One area which would be very controversial and what might be beyond the limits of what could be reasonably done, is to insert new genes into the cells of a living person,”he said. “The reason for this is you cannot be reasonably sure where a gene will land, where it will go. If you just supply new genes to living cells, sometimes a new gene will end up inside another gene and that might inactivate the gene into which it has been inserted. Since this cannot be controlled there would be a risk of all sorts of things happening, possibly even starting a cancer.”

With a dedicated group of collaborators at Cambridge University, Sir John has plans to continue his exploration of cloning technology for a good while yet. “I have funding for a few more years.”

His major focus will be to learn the precise mechanism by which an adult cell nucleus can be reprogrammed back to being an embryo cell, an essential part of the process.

“In other words, to make new cells you really have to reverse the specialised state, go back to the beginning and go off on a different route.

“That’s my major question and we have different ways of trying to answer that. No one experiment will ever provide a complete answer, you just pick away at the problem a little bit here and a little bit there so that in the long run we can answer that question.”

For a man dedicated to asking questions in a laboratory, Sir John is quite comfortable answering them. The Nobel Prize win meant increased attention and a flood of invitations;some, such as the opportunity to present certificates to North Dakota dentistry graduates, were not appropriate, but he expressed gratitude for being asked to speak at Shinawatra University.

“I get a certain number of questions that are way beyond my ability to answer, but I think most people understand that no one can know everything,” he said. “I think when you receive a Nobel Prize you are more subject to people wanting to ask you questions than you are if you didn’t have that award. But I think it’s quite containable.”

Originally published in Spectrum on December 29, 2013.

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