A Stem-Cell Research Pioneer

Professor Austin Smith, 42, is the director of Edinburgh University's Institute for Stem Cell Research, which is recognized as a world leader in this promising new area of science. Stem cells, taken from embryos, are the basic building blocks from which tissues and organs grow. These pluripotent cells, whose development potential hasn't been fixed, have the potential to revolutionize medicine by offering ways of repairing diseased and damaged body tissues.

Born in Liverpool, Smith is Britain's top expert on stem cells. The country has the world's most advanced and progressive policies on research using human embryos. In its 1990 Human Fertilisation & Embryology Act, the British government introduced legislation to legally permit research on embryos for specified purposes, such as treatment of infertility. In 2001, regulations were amended to allow for therapeutic cloning to investigate embryonic development and improve treatment and understanding of serious disease.

Scientists in Britain need a license from the Human Fertilisation & Embryology Authority (HFEA) to work with human embryos as a way to derive new cell lines. One of the requirements for a license is that any cell lines derived from the research must be deposited in Britain's stem-cell bank.

Founded two years ago, the bank is the first of its kind worldwide and is run jointly by the National Institute for Biological Standards & Control (NIBSC) and the Medical Research Council (MRC). It will hold existing and new adult, foetal, and embryonic stem-cell lines in liquid-nitrogen storage. The cells will be available to researchers worldwide once their research is granted approval by a steering committee. Academic researchers will have to pay a nominal fee for the lines, although commercial ventures will have to front the full economic cost. The HFEA is a non-departmental government body that regulates and inspects all British clinicsroviding in-vitro fertilization (IVF), donor insemination, or the storage of eggs, sperm, or embryos.

LICENSE GRANTED. The research is in its very early days, however, and a huge amount of study is still needed to understand how these cells work. Edinburgh University's Smith and his team are focusing on the mechanisms underlying stem-cell self-renewal and their differentiation processes. The goal is that this research will provide scientific foundations for the application of cell-replacement therapies in treatment of human disease and injury.

On Aug. 12, Britain gavescientists permission to perform therapeutic cloning using human embryos. Scientists at the University of Newcastle were granted a license from the HFEA in a bid to becomethe first in Europe to create stem cellsformedical research from a cloned human embryo.It's the first time such a licence has been granted in any European country.

Smith is the first British scientist granted a license to experiment on human embryos in order to develop methods to cultivate stem cells for heart, nerve, and blood-cell therapeutics. He recently spoke with BusinessWeek correspondent Kerry Capell about the status of research, Britain's role, and the impact of moral and ethical questions on stem-cell research. Edited excerpts of their conversation follow:

Q: How did you first become interested in stem cells?

A: From the first time I heard about these cells and what they could do, I was captivated. The fact that they were pluripotent -- it just seemed to me this was where the answer lay. In 1981, embryonic stem cells were first isolated at Cambridge University, about the time I graduated from Oxford. In the early 1990s, we made progress in understanding mouse embryonic stem cells, and it became obvious we could control them. By 1994, we were hoping to replicate what we had done in mouse cells with human cells. At the end of 1994, I applied for the first British license to isolate human embryonic stem cells and derive embryonic stem cells. At that time, under the law you could only get a license to work on these cells for issues of reproductive health, although that has since changed.

Q: What was the attitude of the scientific community back then?

A: At that time, no one else in Britain wanted to touch this area. I was the only one who applied and received this license. Initially, my license was to improve embryo culture for IVF treatment. Once the cells lines were derived, they could be used for other things. The scientific community at the time was against it. People were squeamish and didn't understand why you wanted to do it. The reaction was not quite as hysterical but similar to the reaction scientists working in cloning get today.

I can convince pretty much everyone but the Pope and George Bush that in pre-implantation, a human embryo is not a human being, and it will never be one as long as it's in a laboratory. But that isn't obvious to everyone, including scientists, until you walk them through the argument because of the word "human" and the word "embryo." Now there isn't as much public outcry as there is in the U.S., although I do get letters from people who say they're praying for my soul.

Q: Why is Britain more open-minded on this issue?

A: The regulations are more favorable and, I would argue, more rational. We have a clear and transparent statutory system in place, and there's no distinction between public and private funding as in the U.S. This is because we have already had a long debate on embryonic stem-cell research before enacting the legislation in 1990. So when human embryonic stem cells came along as a reality in 1998, we already had a framework in place that just required an amendment. The legislation was copied by other countries such as Singapore, the second country to develop human embryonic stem (ES) cells.

There were also recommendations to adopt the legislation in the U.S., but they were shelved by successive governments that feared political backlash and the strength of the anti-abortion lobby. This also happened in several European countries as well, although those governments tended to fear backlash from the Catholic Church. Neither the anti-abortion lobby nor the Catholic Church are exceptionally strong forces in Britain. So in that kind of climate, it makes it easier to have a more reasonable debate as it dilutes out some of the hysteria and political fear.

Also, the British scientific community realized this research was important and coherently made the case to the media and politicians why this research needed to be done. If you [the scientist] aren't prepared to articulate why science is needed, then you will lose.

Q: Is there danger that the political debate will get in the way of research?

A: This is just so important. ES cells cannot be left to be the lottery of politicians or public opinion. In the U.S., you have this absolutely ridiculous position on federal funding -- which means most of the best researchers [in publicly funded labs] can't touch these cells while private companies can do anything.

Q: The stem-cell bank is the first in the world. How does it work?

A: The suggestion came out of the debate that we should create a national stem-cell bank. The condition of any license to make human ES cells in Britain is that the cell lines you derive must be deposited in the bank and be available to other researchers. So other researchers who want to work with these cells don't have to work with human embryos, they can get the lines from the bank.

Q: Will this put Britain further ahead in research?

A: In principle, research should move ahead here because of better conditions. But in Britain, they have taken too long to implement regulations and get money out to researchers fast enough. The first grants to researchers are only this year. This should have been happening three years ago. That was the real window of opportunity.

This has been a catalyst and a wakeup call in the U.S. It has stimulated private organizations in the U.S. to fund human ES cell work. There's a lot of activity going on in the U.S. with human ES cells. The impact of the Bush restrictions can still be overcome by those with private funding.

Q: Although Britain has the most conducive environment for ES cell research in the world, are there still some obstacles, such as European Union patent law?

A: Patent law is being invoked as a back-door way to try and regulate research at the European level. There are countries in Europe that are opposed to embryo research, and because they can't get [a ban] through the European Parliament, they're trying another way.

The current law says you cannot patent an unmodified cell from a human. So you couldn't patent a human ES cell in the way it has been done in the U.S. I think this is sensible, as it prevents an unhealthy monopoly. But there's no reason you shouldn't be able to patent the techniques used in manipulating or developing new ways of using them.

This, in theory, is still patentable. But at the moment, the EU patent office seems to be taking a political stance that anything involving a human ES cell should be excluded from patentability because it's publicly offensive. This is potentially very damaging for the European bio-industry. If you can't patent these technologies here in Europe, these companies can't survive.

Q: Your team discovered a key gene in early 2003 that allows embryonic mouse stem cells to multiply indefinitely while still permitting their ability to differentiate. Why is the discovery so important?

A: This gene is a central player in the self-renewal of ES cells. With human stem cells, people are still struggling to learn how to make them and grow them properly in order to develop them into ways that could be used to treat disease. Our approach has been if we can understand as much as possible about the mouse cells then much of this should be relevant to human cells and enable us to get those cells to self-renew efficiently. We named it Nanog after a mythical island off the coast of Scotland. In Celtic mythology, people who went to this island, Tir nan Og, became immortal.

Q: With scientific advances moving so fast, is more at stake today?

A: Yes. There has always been a tension between science and society -- Galileo is the classic example. We have had the genetically modified organisms (GMO) issue in Europe, which was also a case of political mishandling. If these things aren't dealt with properly, then positions can easily be adopted that will hold up progress and affect a country's competitiveness.

Many people in society today aren't scientifically educated, so it can be difficult for scientists to communicate effectively with these people who can feel threatened by developments they don't understand.

Q: Is there a difference between moral and ethical questions in research?

A: There's a formal distinction between the two. Ethics has to do with a codified public system of behaviour, and morality is more of a personal belief. Of course, it's possible to be a scientist and for your morality to tell you that you cannot work with a human embryo. But I would argue that it wouldn't be ethical for such a scientist to argue as a scientist that there was no case for working with human embryos. They can choose not to do it themselves, but they can't make an honest scientific case for not doing it.

Later, Baby

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