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> Stem Cells Frustrate Scientists, Politicians > > By Rick Weiss > Washington Post Staff Writer > Saturday, October 9, 1999; Page A1 > > It has been a year since researchers announced they had discovered in > human embryos and fetuses a unique type of cell with the potential to treat > a host of ailments, including diabetes, Parkinson's disease and even > paralysis caused by spinal cord injury. > > Now, in the final weeks of bargaining over a new federal budget, a > divided Congress is struggling to decide whether the medical promise of > these "human embryonic stem cells" is great enough to justify the use of > taxpayer money to study them, despite the fact that embryos and fetuses > must be destroyed to get them. > > Congress has blocked federal funding of human embryo research for the > past four years, but the discovery of stem cells has upped the ante in the > embryo research debate. The research ban, which is attached to the > appropriations bill for the departments of Labor and Health and Human > Services, underwent several radical changes while the Senate addressed > the bill last week, at various times containing prohibitions far stronger or > weaker than in previous years. On Monday, the House will begin action > on the issue. > > For many lawmakers, it is largely a question of whom they least wish to > alienate: highly motivated and perhaps overly optimistic members of > patient groups who believe that stem cells may soon save their lives or the > lives of their loved ones, or equally passionate antiabortion activists who > believe it is unethical to experiment on embryonic and fetal tissues. > > But for the many publicly funded scientists who want to investigate the > cells, the issue is a no-brainer: The nation ought to enlist their help, they > say, because it is becoming increasingly clear that it will not be easy to turn > stem cells into cures. > > Among the more frustrating problems is how to get the cells to grow into > the specific kinds of cells needed by patients, such as heart cells to be > given to a heart attack victim or pancreas cells to be given to a diabetic. > Today the cells behave as though they have a mind of their own, becoming > whatever kind of cell they choose, and for no apparent reason. > > "You smile at them and they become heart, you frown and they become > brain," complained Tom Okarma, president and chief executive officer of > Geron Corp. of Menlo Park, Calif., which has funded most of the human > embryonic stem-cell work in this country. The challenges ahead, he said, > "are formidable." > > Indeed, while Okarma and others still hold high hopes that stem cells will > lead to medical breakthroughs, ongoing studies by privately funded > scientists at Geron and elsewhere have lent an air of sobriety to a field that > a year ago seemed almost drunk with promise. > > For example, it is still difficult to keep stem cells alive in the laboratory, > and it has been impossible to grow them in numbers large enough to be > medically useful. Moreover, scientists still don't know how to engineer the > cells so they won't be rejected by patients. > > "The only way we're going to figure all this out is to roll up our sleeves and > do the nitty-gritty research," said Harvard University cell biologist Evan > Snyder. "There's such a clamor in the stem-cell field, but we should not let > the clamor or the substantial promise seduce us into thinking we can do > this quickly." > > Embryonic stem cells are the basic, "plain vanilla" cells present at the core > of newly developing animals. During prenatal development, they > differentiate into more specialized cells, such as those that form the skin, > liver, kidneys and brain. > > What makes them unique is their ability to multiply indefinitely in > laboratory dishes, where they can give rise to offspring cells that also have > the ability either to blandly reproduce or, under the right influence, > specialize into any of the body's tissue types. Doctors hope they will be > able to grow a smorgasbord of replacement tissues from stem cells, for > transplantation into people who need them. > > After years of funding from Geron, two research teams announced > simultaneously last fall that they had finally isolated human embryonic stem > cells. One team retrieved them from young human embryos and the other > from the immature sex organs of aborted fetuses. > > The best news so far is that the cells seem to be as immortal as advertised, > said James Thomson, the University of Wisconsin researcher who isolated > human stem cells from leftover fertility clinic embryos. After almost two > years of living and dividing in laboratory dishes, every new generation of > cells seems just as young and full of potential as the previous one. > > To prove that, Thomson has injected into mice freshly grown human stem > cells that are more than 300 generations removed from the parent cells he > isolated from his original human embryo. Stem cells that have retained > their full potential should, when they are injected into mice, differentiate > into all the many kinds of tissues that they can become. And these > 300th-generation cells have done so with exquisite creativity, Thomson > said, with some of them becoming hair, others teeth, and still others little > masses of cardiac cells that soon begin to beat in unison like a miniature > heart. > > In fact, it is not difficult to get stem cells to differentiate into various tissues. > The hard part is growing them into the specific kind of tissue you want – > and keeping them from specializing until you are ready. Scientists will have > to grow huge vats of stem cells in their undifferentiated state if they are > ever to commercialize them. Currently, however, the only way to keep the > cells in this "primordial" state is to grow them in small dishes along with a > special type of mouse cell. > > The mouse cells – known as "feeder cells" – somehow keep human stem > cells from spontaneously following their urge to specialize. But despite > valiant efforts, Thomson and others have failed to identify how the feeder > cells do that. It is a bottleneck scientists will need to get through if the > research is ever going to become useful for patients, because the > mouse-cell system is too cumbersome to scale up to commercial levels. > > It's not an impossible task. Several years ago, researchers working with > mouse embryonic stem cells were in the same bind: Those cells only > retained their full potential when grown with finicky feeder cells. Then > researchers found that a compound secreted by the feeder cells, called > leukocyte inhibitory factor, or LIF, was the magic substance that was > keeping the stem cells vital. Since then, scientists have just had to add > some LIF to their dishes of stem cells, eliminating the need for feeder cells. > > "After that, the mouse studies took off," recalled Roger Pederson, a > Geron-supported researcher of human stem cells at the University of > California at San Francisco. Unfortunately, LIF does not do for human > stem cells what it does for mouse stem cells, Pederson said. "Someone > has to discover the LIF counterpart for human stem cells." > > Perhaps even more daunting is the task of learning how to prod batches of > stem cells to mature into specific kinds of cells for transplantation into > people, such as liver cells for patients with cirrhosis or specific kinds of > brain cells for patients with Alzheimer's or Parkinson's disease. > > Scientists have had some small successes in encouraging stem cells to turn > into desired types, such as blood cells and nerve cells. > > Last December, for example, Johns Hopkins University researcher John > Gearhart stood before a Senate subcommittee and unveiled a poster-size > photograph of spidery living cells with branched, outreaching arms. These > appear to be healthy human brain cells, said Gearhart, grown in a > laboratory dish from a starter batch of stem cells by feeding them a special > recipe of nutrients. He plans to inject some into the brains of rodents this > fall, to start assessing their potential as a treatment for brain diseases. > > But Gearhart's method is far from foolproof. Many stem cells treated with > the same nutrients do not become neurons, and retain the potential to > become bone, muscle or other cells later on – cells that would not be > welcome in a patient's brain. > > Even less is known about how to spur stem cells to grow with assuredness > into other kinds of cells, such as the insulin-secreting pancreas cells that, > given the prevalence of diabetes in this country, are foreseen by Geron as > the first "blockbuster" moneymakers. Somehow, researchers will have to > overcome stem cells' apparently fickle nature. > > Finally, there is the problem of immune-system rejection. Researchers > want to figure out which molecules on stem cells are recognized as foreign > by a patient's immune system. In theory, researchers could genetically > engineer the cells to lack those molecules – a simple-sounding strategy > that scientists concede will probably take many years to implement. > > Depending on who is talking, problems such as these add up to an > argument either for, or against, a quick infusion of federal funds. > > To some on Capitol Hill, including Sen. Arlen Specter (R-Pa.), the many > difficulties scientists face suggest that federal funds are needed if cures are > to be developed within the next decade. Federal funding also would > ensure a level of public oversight not possible when research is left to > private concerns. > > But others, including Rep. Jay Dickey (R-Ark.), say that given the vast > number of unanswered questions in the field, the government could satisfy > itself by funding basic studies on animals and less controversial human > cells, without venturing into the ethical minefield of embryo research. > > Further complicating the political problem, preliminary evidence from mice > suggests that stem cells retrieved from embryos may have medical > advantages over those isolated from aborted fetuses. That revelation, > described in the Oct. 1 issue of the journal Science, is problematic for > legislators such as Dickey. Last week, he sought to reword the ban in a > way that would have precluded research on embryo cells while allowing > studies on aborted fetuses. Fetal research is less controversial than > embryo research, because the former can be done on fetuses already > aborted but the latter involves the direct destruction of embryos. Dickey > later withdrew the proposal. > > In the end, Congress may manage to duck the issue. During the past few > months, the National Institutes of Health has created a set of guidelines > and ethical standards that publicly funded scientists wishing to study > human embryonic stem cells would have to follow. > > The guidelines would preclude researchers from retrieving stem cells from > embryos directly, because that act causes the destruction of live embryos. > But researchers would be allowed to study stem cells from embryos that > someone else had destroyed or from aborted human fetuses. > > Many in Congress see the guidelines as a good compromise – and as a > way to eliminate at least one controversial element from a bill that is > already making waves with provisions relating to abortion and birth > control. On Thursday, the Senate passed its version of the HHS bill with > no restrictions on stem-cell research. > > On Monday, the House will take up its version of the bill. And if > representatives decide they can live with the NIH guidelines – a far from > foregone conclusion – they too may drop the ban. > > But the suspense might not end there. Many Congress-watchers predict > that the House and Senate versions will defy congressional consensus on > other counts, and ultimately will get folded into a huge omnibus spending > bill. > > Omnibus spending bills are negotiated outside the usual committee circles > and are famed for ending up with unexpected changes – the result of > horse-trading efforts in the wee hours of an already extended budget > process. That means that, for all the lobbying on both sides of the issue, > the legislative resolution to this year's biggest biomedical controversy may > not become clear until the dust settles at the end of a frantic, closed-door > session. > > © 1999 The Washington Post Company > > Back to the top > >