>                   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
>
>