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The Ten Years of Dolly: Past, Present and Future

Wednesday 14 February 2007

The Royal Museum of Scotland, Chambers Street, Edinburgh

The Royal Society of Edinburgh and the National Museums of Scotland Evening Public Discussion Forum

Key Points

The birth of Dolly heralded a step change in science

Dolly became a symbol for the potential benefits and threats of biotechnology

Since Dolly nuclear transfer technology has been used to clone other animals but most research is now taking place in the Far East

Some scientists fear that public attitudes, media hype and misplaced fears about human cloning have clouded the potential benefits of this technology

Human reproductive cloning is unlikely, is scientifically probably not possible at the moment and would raise huge ethical questions

Embryonic stem cells created using cloning techniques have potential in finding therapies for a range of human diseases

The ethical questions are not straightforward and there needs to be more public debate

Introduction

Ten years ago in February 1997 Dolly the sheep was unveiled to the world. Created by scientists at the Roslin Institute near Edinburgh, she was the world’s first cloned mammal.

Since then the same nuclear transfer technology has been used to clone a host of other creatures, including cows, pigs, cats, dogs and, possibly most recently, ferrets in 2006.

To say that Dolly caused a sensation is no exaggeration. She attracted worldwide media attention and even the then president of the United States demanded that an expert group be convened forthwith to report to him personally on the implications.

As well as being a wonder in her own right Dolly was exciting for the possibilities she heralded. Would nuclear transfer technology revolutionise agriculture, helping to breed better, stronger livestock? Could cloning techniques be used to find treatments for human disease. And, most dramatically, could it be that Dolly was the first stage of a process which would lead to the cloning of man?

The RSE (Royal Society of Edinburgh) and NMS (National Museums of Scotland) brought together a panel to discuss these issues and others. Science and ethics were represented by the speakers, Dolly ‘inventors’ Professors Ian Wilmut and Keith Campbell and Dr Donald Bruce, director of the Church of Scotland’s Society, Religion and Technology Project and Professor Alan Holland, a philosopher.

The event was chaired by Professor Grahame Bulfield CBE FRSE, Vice-Principal and Head of the College of Science and Engineering at the University of Edinburgh. It was introduced by Jane Carmichael, NMS Head of Collections.

Speakers

Professor Alan Holland, Emeritus Professor of Applied Philosophy, University of Lancaster

Dolly – Cracking Nature’s Mould?

Using a quotation from King Lear, Professor Holland raised questions around what is natural and what is unnatural or against nature. Specifically he asked if Dolly had ‘cracked nature’s moulds’.

Asking how ‘one little lamb could cause such a furore’ he concluded that the short answer was that Dolly raised the spectre of human cloning – and this bothers people.

Opinions expressed here do not necessarily represent the views of the RSE, nor of its Fellows

Ordinary folk who express unease about some applications of genetics, saying it is ‘against nature’ are often condemned by scientific experts, he said. But he tended to side with ordinary folk, on the assumption that they are protesting about what goes against the norms or habits of nature.

Nature operates by trial and error, he said, so her habits or norms are a good indicator of what works.

Cloning works against the norms of nature, he said. But he added that while cloning might have some useful applications in, for example, animal husbandry, it is not an end in itself.

He said the lasting legacy is likely to come from the nuclear transfer technology that produced Dolly. In his view using this technology to help people with inherited diseases should not be judged ‘unnatural’.

He concluded that it was unwarranted to assume that what is unnatural is therefore wrong and said that even if there was agreement on what unnatural meant, there was still hard ethical thinking to be done.

Professor Keith Campbell, Professor of Animal Development, University of Nottingham

Dolly – Did she open a gateway to the future?

Professor Campbell gave a brief history of the uses to which nuclear transfer technology have been put since the birth of Dolly, discussed its potential and asked whether the debates on possible misuses of it had obscured the potential benefits.

Since Dolly, many other mammals have been cloned using nuclear transfer technology – that is, using the DNA of an adult mammal to create another mammal. These include farm animals, such cattle in 1998 and pigs in 2000, rare breeds such as the banteng in 2003 and companion animals, including a dog in 2005.

There are various reasons for doing this. For example, rebreeding good genes into cattle can improve the dairy industry. Similarly animals can be bred to be free from certain viruses and rare breeds can be maintained.

Other uses and potential uses are include creating drugs, disease research, creating produces such as clotting factors for people with diseases such as haemophilia and potentially creating organs for xenotransplantation.

Professor Campbell said that the birth of Dolly has also opened debate about the use of technology and particularly potential for use in human reproduction or in production of embryos to obtain embryonic stem cells. The fear that humans could be cloned and the anti-GM lobby have, he believes, meant that hardly any research in this area is now taking place in Europe or America. In his view, the UK has not made the most of the discovery.

Professor Campbell is against reproductive human cloning but believes that there is real potential in therapeutic cloning. He believes that science is doing what man has been doing for generations [in terms of improving genetic stock] but that stem cell technology has the potential to speed the process up and opens the door to a range of therapeutic possibilities.

Dr Donald Bruce, Director, Society, Religion and Technology Project, Church of Scotland

Dolly – Icon or Iconoclast?

Dolly became an overnight icon, said Dr Bruce. She signalled a step change in science and genetics and became a symbol of the promise and threat of biotechnology.

Although the Roslin Institute saw cloning as an agricultural tool, the media and policy focus was on the potential of human cloning. This focus, Dr Bruce believes, clouded the debate over the ethics of animal cloning.

Although perhaps not inherently wrong, there are welfare issues around animal cloning, including the risk of developmental abnormalities, but it could be justified if there was a reasonable balance between potential benefit and risk, he said.

Questions remain over turning animals into widgets on production lines, however.

He believes that human reproductive cloning is immoral because of the physical risks but also because of ethical questions. These include whether each person should have his or her own genetic identity.

But he warned that pressure for medical discoveries had already led to fraudulent research claims in Korea, which he said was perhaps a warning not to push too far on speculative applications.

Dr Bruce discussed the findings of the Church of Scotland 2006 Stem Cell Study, which convened a group of experts to review the science and the theology and to assess particular applications, including embryo stem cells and cloned embryos.

Opinions expressed here do not necessarily represent the views of the RSE, nor of its Fellows

The Church of Scotland General Assembly has taken a view on aspects of stem cell technology, concluding, for example, that it is acceptable to make limited use of surplus embryos created for IVF as they would be discarded otherwise.

But it is less in favour of creating embryos for research, although there might be exceptional situations where it is acceptable, for example to produce diseased cells for research which could not be created in any other way.

He also outlined different views on the moral status of the human embryo, saying that while some saw it as a ball of cells, others accorded it the same moral status as a baby, while others gave it a gradual moral status.

He raised other ethical issues, including the moral status of human-animal ‘hybrid’ embryos, saying they had a degree of moral status.

He concluded that neither straight science nor religious groups had all the answers and that there was a need for proper public dialogue. Novel science should work within public values, he said.

Professor Ian Wilmut OBE FRS FRSE, Professor of Reproductive Science, University of Edinburgh Centre for Reproductive Biology

Cells from Cloned Human Embryos for Drug Discovery

Professor Wilmut outlined the possibilities of using the nuclear transfer technology developed at Roslin to study genetic conditions. In particular, he referred to his own current research into MND (Motor Neurone Disease), a relentlessly progressive condition for which there is no cure or effective treatment.

To develop new therapies it is essential to understand the cause of human genetic disease, he said. In MND around 2 per cent of cases have a mutated gene (SOD1) and a further eight per cent of cases are inherited, although the specific genetic cause has not been identified.

If cloning techniques can be used then knowledge of the mutations are not necessary.

The research involves transferring a cell from a patient with inherited MND into an unfertilised human egg which has had its genetic information removed, and creating an embryo from which stem cells can be derived.

The cells could be compared to those from healthy embryos to see what happens when they begin to develop the abnormalities associated with MND.

This could improve understanding of the disease and be used to screen potential drug treatments.

Professor Wilmut said there were practical difficulties in using human eggs, including limited supplies, ethical concerns and the problem that the likely efficiency of cloning would be very low.

He pointed out that there were no lines from cloned human embryos so far, nor from non-human primates.

Using more freely available rabbit eggs was a possibility, however, which could help us understand better how to use human eggs. There is also the possibility that rabbit eggs are so similar to human eggs that they could be used to study human disease.

Professor Wilmut acknowledged ethical concerns but pointed out that the embryos were not implanted, not conscious and were a very small bundle of 200 cells.

He concluded that ambitious research should be continued, but that application of it should be cautious.

Discussion

The discussion centred on four main areas: the moral status of embryos, what constitutes a ‘hybrid’ embryo and what rights it should have, whether there are lines which simply should not be crossed and whether compassion for people with disease should over-ride other moral concerns.

It opened with a member of the audience from St Andrews asking Dr Bruce why, if the Church of Scotland thought it reasonable to use discarded IVF embryos and was therefore tacitly approving the creation of embryos, it was not in favour of creating embryos specifically for research.

Dr Bruce said there was a difference in using embryos which had been created for another purpose and which would otherwise be discarded and in actually taking a decision to create something for research purposes. He pointed out that the church’s view was divided, but asked where lines should be drawn, for example, at using stem cells to create ‘spare parts’.

Opinions expressed here do not necessarily represent the views of the RSE, nor of its Fellows

The chairman, Professor Bulfield, brought up the issue of hybrid embryos, which Dr Bruce said raised ethical difficulties. He was backed by Professor Holland, who asked about the moral status of human DNA in a rabbit egg but questioned whether this would be a human being in the ordinary sense.

Professor Wilmut pointed out with some force that scientists wouldn’t be going to all that trouble if it wasn’t that important benefits could ensue. He said he was surprised that compassion for people with ‘he llish’ diseases didn’t have more of an effect – and said that people’s attitude to stem cell research tended to become more favourable if they knew or met someone with a disease which might be helped.

He described meeting the former Celtic and Scotland player Jimmy ‘Jinky’ Johnstone shortly before he died from MND, comparing his fleetness of foot on the pitch with the man unable to move from the neck down. And he said that was a real motivation to find something which would work.

A retired biologist in the audience said the term hybrid was inaccurate. Professor Wilmut said it was a pseudo hybrid, really, and Dr Bruce said that whatever it was called, the issues remained.

Professor Holland raised the issue of what is natural – backed by Dr Bruce who said the public has concerns about the using pig hearts, for example, in human transplantation, partly because of a ‘yuk’ factor, partly because of the ideas we have about the heart, but that public attitudes could change and develop.

The audience member from St Andrews asked the final question, raising the concern that those who were against embryo testing had a lack of moral imagination because they couldn’t see the research was for a good end.

Dr Bruce pointed out that there were different sets of moral values – and that to some people, the use of embryos was akin to the actions of Burke and Hare, in that it could be seen in their view as taking life for medical research.

Other issues raised were around the difficulty of getting eggs from primates – hence there have been no cloned primates as yet, although Professor Campbell said there was a lot of research in that area in the Far East.

Opinions expressed here do not necessarily represent the views of the RSE, nor of its Fellows