> 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
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