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The source of this story is the Melbourne AGE: http://tinyurl.com/7bx8a Additional graphic how therapeutic cloning works: http://www.theage.com.au/media/2005/06/10/1118347600436.html The hard cell By Jo Chandler June 11, 2005 Some time before December, Australians must decide whether to allow scientists to explore the next great frontier: the cloning of embryos for stem cell research. The lobbying has only just begun. In biotech frontier country, in a small laboratory in suburban Clayton, it's always a sweltering 38 to 41 degrees. Here some of the most contentious creatures ever cooked up in a test tube - tiny, cloudy dots, each a colony of 1000 to 10,000 cells - spend their days bathing in a petrie dish of pale-pink growth culture. Each morning they are briefly, carefully, removed from the nurturing warmth of the incubator and given a check-up under the microscope. They are the latest in a long line of cells that began life in a human embryo in Singapore and then took a plane trip to Melbourne in a scientist's shirt pocket, before being isolated at Monash University eight years ago. They are called HES3. No romance in that: they are labelled for what they are - human embryonic stem cells. They are the incarnations of 30-odd cells extracted from the core of a five to seven-day-old human embryo, destroying it in the process. They have multiplied and been divided countless times over the years, perversely eternal, replenishing with each dissection like the Magic Pudding. They have the capacity to grow into every organ, tissue and bone of the human body - this is their power, their "pluripotence". They are the genesis of our being, and one day may be the salvation of many lives, but they will never be people. And here they are, centre stage under the microscope of Monash University research scientist Elizabeth Stadler. "Here's a nice colony of undifferentiated (stem) cells," she says, obligingly pulling them into focus. "Undifferentiated" means they are poised on the brink, their future unknown. They may grow up to be neurones or muscles, livers or hearts, skin or guts, like a crop of 14-year-olds selecting next year's subjects. Biology or geography? Scientist or carpenter? Poet or bus driver? "Beautiful," Stadler says. Beautiful, yes. Controversial, always. And about to become more so. Three years ago, the Federal Government opened the door to research on embryonic stem cells, but only in tightly controlled conditions, and only with cells derived from "spare" in vitro fertilisation embryos. The Government outlawed the creation of clone embryos, a disappointment to many scientists. Not because they wanted to clone humans, but because much of the potential of embryonic stem cells swung on their capacity to be "customised" to individuals. The human embryonic sterm cells from the Australian Stem Cell Centre at Monash University. The Prohibition of Human Cloning Act 2002 introduced a three-year ban on the creation of a human embryos for any purpose. This expires in December. Australians will then need to decide whether to impose a further ban on cloning or just on reproductive cloning, effectively allowing therapeutic cloning. This is what many in the white-coat brigade want to persuade the Government to do, and what their opponents are determined to prevent. Therapeutic cloning was proved to work efficiently only last month when in a stunning announcement scientists in South Korea said they had successfully cloned 31 human embryos. It is a milestone ranked with the birth in 1997 of Dolly the cloned sheep, although minus the picture opportunities. None of the dozen or so experts interviewed for this article advocated reproductive cloning. All backed a criminal law prohibiting it. But the breakthrough makes an already messy ethical dilemma murkier. It is one thing to gain some research benefit from embryos that would be wasted, like the IVF spares. But to create embryos for their parts? Scientists in 2002 were unable to persuade the Howard Government that the scientific case to wade into this territory was worth the grief. The concept of "cloning" was just too fraught. But now they are preparing for another crack at it. And this time they are choosing their words carefully. The process is rightly called nuclear transfer, not therapeutic cloning, they insist. They want to make cell lines, not people. Dr Martin Pera is the research director of the Australian Stem Cell Centre's embryonic stem cell program. His pitch is carefully cautious. Pera and many of his colleagues fear the hype surrounding the still unproven potential of embryonic stem cells could poison rather than support their case. So they're changing tactics, selling the message that this technology is not just about producing tailor-made spare parts or repair kits for diseased bodies, although that's still the scientists' dream. Along the way, the science could also provide a platform for a new generation of drugs and to watch how disease progresses, they say. Researchers have been excited about this possibility for some years, but it has not featured much in public discussion. "Until now, in terms of models of disease, we have really been limited to animals or direct experimentation on human beings, not a lot in between," Pera says. But with embryonic stem cells made from cloned embryos of humans with diseases such as Parkinson's or Alzheimer's or motor neurone disease, "we can have dishes of whatever human cell types we want to study in the laboratory", a huge advantage on the past. "It's using stem cells as a discovery tool to make new medicine," he says. "It's about disease-specific stem cells as opposed to patient-specific ones," Dr Megan Munsie, development manager of the private company Stem Cell Sciences Ltd, says. The company works with researchers at the Australian Stem Cell Centre and is also at Clayton. "When this whole area first attracted attention, it was because it was seen as a way of generating cells that would not be rejected, derived from a patient's own DNA. That's what we promoted. But that might not be necessary, and it is not the only use of this technology," Munsie says. So instead of giving someone an injection of custom-built neurones to cure their Parkinson's disease - the stuff scientists dream they one day might do - the research might work just as effectively by producing drugs tested on banks of generic Parkinson's cell lines. Or they might provide a means to an end - a bridge to a less ethically charged landscape. "Studying the reprogramming phenomena that goes on during cloning offers an avenue to understanding how we might be able to reprogram an adult cell, so that maybe one day we can make patient-matched stem cells without using eggs and without making an embryo," Pera says. This recasting of the potential of embryonic stem cells and therapeutic cloning might seem inconsequential, even semantics, to the casual observer. But as the message creeps out, it is causing unrest, even outrage, among ethicists and commentators already uncomfortable with the morality of the research. Father Bill Uren is a Catholic commentator with a reputation as a moderate, rather than a hard-liner. But what he is hearing from the laboratory lobbyists has his hackles up. "I can't see it as anything else but a con not to have put this up fairly early in the debate," Uren says. He says the research so far has "not met the hype" and scientists are trying to reposition themselves. "I think the public is being sold a pup," he says. Elizabeth Stadler says it took her about a year of staring down a microscope at the HES3 creatures for her to begin to understand them. To learn to read their foibles, to recognise their features as they grow - a certain firmness in their outer cell walls, a hint of density at their core. To know the moment when they are ripe for division or for a gentle nudge into the career she wants for them - as red blood cells. Stadler dreams of one day turning these cells into buckets and buckets of blood. No more pleas for donors at the blood bank. But for now, she's content with the cells dutifully marching into bloodhood in modest, microscopic numbers. Stadler has good hands and good eyes, says her boss at the Monash Immunology and Stem Cell Laboratories, Dr Andrew Elefanty. Here, on the frontier where researchers work with no maps to guide them, science is as much about art and instinct as laboratory notes, he says. In the fiercely competitive field of stem cell research, these are the qualities that will give a laboratory the edge. They are the skills Australia stands to lose if the moratorium on therapeutic cloning remains, according to one of the key arguments of the science lobby. If the law does not allow work in these areas, the skills will drift to laboratories in countries where processes like therapeutic cloning are allowed, in particular Britain, Singapore and South Korea. Scientists will be taking every opportunity in the next few months to educate the public about their work. "I'm still old enough to remember the first heart transplant, and speculation that if you got someone's heart, you would get their soul as well," Dr Richard Boyd, of Monash University, says. "You must bring the public with you." Expect a multi-media effort to decode very complex biological pathology into a concise, cogent, easily digestible storyline. Another strategic target will be persuading politicians and the community that the structures are there to protect society from mad or bad scientists. This may be as tricky as some of the technical work. A survey by Swinburne University late last year showed that 54 per cent of people approved of the use of stem cells taken from spare IVF embryos. But only 36 per cent were in favour of research using cells created by cloning. "We believe there are true benefits from this research, and we believe we can do it well here and do it ethically, with better controls than in some other countries," the Australian Stem Cell Centre's chief education officer, Professor Graham Jenkin, says. But most enticingly, the science lobby will continue to offer the hope of freeing us from our most lethal and debilitating afflictions. Professor Alan Trounson - IVF and stem cell pioneer and stirrer (last week he suggested the use of eggs from rabbits to create therapeutic clones) - says that at the top of his wishlist, if the technology were allowed, would be to take cells from cancer patients to start embryonic cell lines that might demonstrate the genetic drivers behind the disease. "And also to examine how they express themselves, and if there is some way of blocking them," he says. "Or of taking a cell from an Alzheimer's or a Parkinson's or a motor neurone disease patient, and see the phenotype develop in the laboratory. "It gives you the opportunity to work on the prevention of disorders. To prevent or slow down or even reverse them." That's the scientific case. So what of the ethical concerns? "In my view, the ethic is really the benefit versus the cost," Trounson says. Here the cost is to use a cell, or so-called nuclear transfer embryo, which has very little developmental competence at all, and use it to generate new information that could be used to - potentially - cover a very broad range of patients with diseases. "I don't see that the embryo is a person, so I don't see it as immoral, whereas someone else will. It's not a matter of morals, it is about being ethical, to follow that line. I think it would be a strange ethic that didn't encourage us to explore this," he says. This is the argument put most forcefully by Melbourne ethicist and Uehiro chair in practical ethics at the University of Oxford, Julian Savulescu. He rates the potential applications of therapeutic cloning - both for self-transplantation of healthy cells and for the development of cellular models for diseases - as being on a par with splitting the atom, but vastly more beneficial to humanity. "To fail to do beneficial research is as wrong as doing harmful research," he argues in a recent paper. "To fail to release a drug which will save 100,000 lives is morally equivalent to killing 100,000 people." Savulescu, back in Melbourne this week, sees a difference between the moral status of wanted and unwanted embryos. They have a special status when they are part of a project to have a child, as in IVF, he says. When they are not, they have a lower status, which is why people are allowed to discard "spare" IVF embryos when they have completed their family, or have abortions, or use an IUD to prevent implantation of an embryo as a means of contraception. Woo Suk Hwang, the South Korean scientist who made last month's breakthrough when he created 31 human embryos through nuclear transfer, is emphatic that he has created cell lines, not clones. But they do have a moral status, he says. He told Time magazine this month he makes sure at least one of his researchers keeps the cells company all day and most of the night as a way of nurturing respect for them. "In this kind of work, you need to insert the human spirit," Hwang says. Sydney Bishop Tony Fisher, a member of the Catholic Bishop's Committee for Doctrine and Morals, says the church regards therapeutic cloning as worse than reproductive cloning. "At least in the case of reproductive cloning, you are intending to give these embryos life," he says. "In therapeutic cloning, the purpose is to create human beings only to destroy them. So from that point, it is more grotesque and ethically problematic." There is a broad range of views within science, religion and the Catholic debate on when life begins - with more liberal commentators taking the line that early cells are not potential humans until day 14 or so of development, when they implant in the womb wall and develop characteristics known as the "primitive streak". Another "escape clause" for the morally tied is to see the product of nuclear transfer as something other than human because it is not the consequence of a sperm fertilising an egg, but of an adult cell inhabiting and developing within a hollowed egg. But Fisher sees no room for equivocation. "The entity that results is an embryo," he says. "You can keep changing the name but given the right environment (a womb), it will develop like you or I did." He sees the scientific lobby as relentlessly, and cleverly, pushing the boundaries by captivating the community with the emotive stuff of human suffering, and yet, "I don't think they are really any closer today to delivering than they were a few years ago". Savulescu's argument - that it is immoral not to proceed given the promise - "from a philosophical point of view is a real howler". All manner of therapies, treatments and experiments - including the work of the Nazis - might achieve results, but that doesn't justify them, he says. Uren takes a different view. "I'm against cloning - reproductive or therapeutic - because it destroys morally significant human life," he says. "But if I did believe it was OK - which I don't - I would have thought that therapeutic cloning was the way to go." His view rests on the belief that while the product of nuclear transfer is an embryo, due to the nature of its reproduction, its chances of successfully developing are remote. Uren is disturbed by the argument that scientists are in an international race - a competition for the stem cell prize - and that the rules must change or we will fall behind. Such a line does not support the notion that this science is about the good of humanity, he says. It smacks more of a race for individual glory or profits. Professor Agnes Bankier, director of Genetic Health Services Victoria, also has some personal concerns about using therapeutic cloning to produce patient-specific embryonic stem cells. "I don't have a problem with research on spare embryos," she says. "These would be discarded if they were not used, and there is a potential benefit to do research on them. "But I think cloning is a little more problematic. If you are creating embryos, there is the issue of what you are putting the woman through to harvest her eggs to create those embryos, and there are some risks. "I think it is different if women chose to take those risks for the purposes of reproduction - women have always taken risks for reproduction. But to be put through it for research, one could question if it really is to their benefit." In the next few months, HES3 will be joined in the incubator by MEL1 or MEL2, two of the new embryonic stem lines produced by the private Stem Cell Sciences and Melbourne IVF - from spare IVF embryos. The MEL is for Melbourne. It will be a challenge working with a new line, Andrew Elefanty says. He hesitates to use the metaphor in this charged debate, as it will without doubt come back to bite him. But these cells are a little like children, he says, with their own quirks and personalities. What special qualities MEL will bring to his efforts - alongside colleagues Ed Stanley and Elizabeth Stadler - he does not yet know. Similarly, what working with cell lines produced from therapeutic cloning will do for his work, he also doesn't know. But he argues that he ought not need to prove anything at this stage. "Medical therapy has always been incredibly pragmatic and incredibly empirical," Elefanty says. "And it has been quite happy to prostitute itself in the sense of trying anything and seeing what works If we don't, we stay where we are and we stumble along." Science is about exploration, not certainty, he argues. A STEM CELL PRIMER What are they? Cells that can develop into other kinds of cells. They can be derived from embryos, adults and umbilical cord blood. Why all the fuss? They have enormous potential to provide custom-made repair kits for people with diseases, including diabetes, Alzheimer's, Parkinson's, Huntington's, motor-neurone disease and even spinal cord injuries. They can also be used to produce diseased human cells for research and drug development. But they are unproven. Scientists do not know what would happen if transplanted stem cell derivatives were transplanted into a human. Why the controversy? Few people have ethical concerns about using stem cells from adults or umbilical cords. But taking them from embryos - even spare ones to specifically harvest stem cells - raises ethical and moral questions. People troubled by these issues want research limited to adult and cord cells, but many scientists believe embryos will deliver the most powerful medical tools. What's cloning got to do with it? It's a way of generating specific types of stem cells. By putting an adult cell into a hollowed human egg, a clone embryo is created. In therapeutic cloning, the embryo is allowed to develop for five to seven days and is destroyed when the stem cells are extracted. This differs from reproductive cloning, in that the intention is not to allow the embryo to develop. But the technology is similar. An embryonic stem cell created from a clone is custom-made for an individual. The clones could also create disease-specific cell lines to develop drugs and other treatments. What is the legal situation in Australia? It is illegal to experiment on naturally conceived embryos. Embryonic stem cells are taken from "spare" embryos from eggs fertilised in an IVF clinic - embryos that would be discarded - and are donated by the parents for research. Therapeutic and reproductive cloning is prohibited. And elsewhere? Scientists in Britain, Israel and private organisations in the US are permitted to create embryos through therapeutic cloning. Laboratories using these techniques are also in South Korea, Singapore and China. What happens next? A legislative review of human cloning and embryo research in Australia is due to be completed by December 19. The Federal Government has yet to announce the committee and its terms of reference, sparking concerns the debate will be too hurried. The federal Minister for Ageing, Julie Bishop, is overseeing the review. ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn