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Stem cells Loose change Mar 1st 2001 From The Economist print edition CELLS in the body, like workers on the job, can get stuck in a rut, doing the same old thing day after day without prospect of promotion or relocation. When change comes, it can be for the worse: adult cells locked in dead-end positions as skin or kidney cells, say, sometimes take on dramatically different properties, but usually as part of a nastier turn of events, such as cancer. Alan Colman and his colleagues at PPL Therapeutics, a Scottish biotechnology firm, have been trying to give such cells a second lease on life. At a recent meeting of British fertility experts, they claimed to have found a way to coax adult skin cells from a cow into becoming heart-muscle cells-in the laboratory, at any rate. Such reprogramming of adult cells has long been the goal of those interested in so-called "therapeutic" cloning. Cloning, or nuclear transfer, involves shifting the nucleus of an adult cell into an egg which has had its nucleus taken out. The resulting cell, or zygote, then has all the genetic material and biochemical machinery it needs to get on with the business of becoming an embryo. It also becomes a ready source of embryonic stem cells which can transform themselves into the different cell types needed to build a body. Most adult cells lack this versatility. But when their nuclei are transferred into eggs, something happens which gives them the potential to get into new lines of work. Many researchers, and needy patients, are hopeful that embryonic stem cells might one day provide a supply of replacement tissue for organs worn out through disease and old age. Because the transplanted nucleus could come from one of the patient's own cells, the resulting stem cells would be genetically identical to the donor. Therefore any "spare parts" grown from such cells and popped back into the patient might avoid the problem of tr ansplant rejection which comes with genetically mismatched grafts. But cloning is a troublesome business. Experience with species cloned thus far, including sheep, cows and pigs, shows it to be very inefficient; according to one estimate, it would take 280 human eggs to produce a single line of embryonic stem cells. Human eggs are in short supply, and hard enough to obtain for routine in vitro fertilisation, let alone to meet the additional demands of therapeutic cloning. There are ethical dilemmas to deal with too. Therapeutic cloning is essentially the same as reproductive cloning, but without the final step of implantation in a woman's uterus. Regulations in Britain, which were recently amended to allow research into therapeutic cloning, stipulate that the cloned embryo must end its days in the laboratory within 14 days of creation. Even with this safeguard, together with stern prohibitions on the repro ductive cloning of humans in most countries with sufficient resources to do it, many feel that therapeutic cloning is a step too far. If researchers understood what exactly happened in the "reprogramming" process to reinvigorate the transplanted nucleus, they might be able to repeat it on adult cells directly, without having to go through the cloned embryo step. This is essentially what Dr Colman claims to have done, creating a line of cells which, in the test tube, look like embryonic stem cells, and some of which turn into a cluster of heart cells that beat. How Dr Colman's team has done this is a mystery, since the group will not reveal its method until its patents have been sorted out. Even Dr Colman is unsure whether he really has stem cells on his hands: he needs to show that the altered skin cells can produce other cell types, as well as heart cells. Despite this uncertainty, many have greeted PPL's work as a way around the tricky business of working with stem cells derived from human embryos, cloned or otherwise, causing the firm's share price to leap. But John Gearhart, a stem-cell expert at Johns Hopkins University in Baltimore, warns that it would be rash to give up on human embryonic research, which is showing promise in treating animal models of paralysis and other disorders-though scientific and commercial obstacles mean that routine therapy for humans is still far off. When it comes to stem cells, it is far too soon to write off, or buy into, any one approach. http://www.economist.com/science/displayStory.cfm?Story_ID=518236 **********