By Rick Weiss
Washington Post Staff Writer
Wednesday, April 19, 2000; Page A01
In a laboratory in Baltimore, tangles of healthy neurons are sprouting from the spinal cords of mice stricken with a rodent version of Lou Gehrig's disease, a nerve-withering ailment for which there is no cure.
In Boston, mice that normally die in their first six months from the same disease are living a year and a half or longer.
And in a nearby Boston lab, monkeys whose motor neurons have been experimentally destroyed are growing new ones.
In all three cases, the animals were treated with embryonic stem cells, a class of cells found in human embryos and fetuses that can nourish ailing cells and grow into virtually every kind of tissue. Discovered just 18 months ago, the cells appear to have remarkable regenerative powers useful against a host of conditions, including Parkinson's disease, diabetes and, perhaps, even cancer.
But equally remarkable is the speed with which privately funded researchers leading these and other studies are moving to test their stem cells in patients. Meanwhile, publicly funded scientists remain banned from the field because federal guidelines for the ethical conduct of stem cell research languish unfinished, the victim of political wrangling over abortion.
At least one team of privately financed scientists has already met with Food and Drug Administration officials to outline strategies for starting human tests next year. And in Wisconsin, an entire stem cell research facility has just been built without a single federal dollar, to distribute human embryo cells to scientists who plan to test them in volunteers here and abroad.
The accelerating private push is thrilling patients who hope to see medical benefits in their lifetimes. But it's worrisome to some ethicists and others who believe the public would be served better if Clinton administration officials would finalize and release their long-awaited rules for how the embryonic cells should be obtained and used.
Among the concerns are that parents may not be told that their embryos are being used in research; scientists may start creating human embryos from scratch just to destroy them for their stem cells; and someone may even try to use the versatile cells to clone human adults.
The rules, which would be designed to prevent these and other abuses, would be binding only on federally funded researchers. But they would serve as the gold standard for everyone in the field. If federal officials don't promulgate them soon, some say, the field of stem cell research could end up a lot like the fertility business, another area of medicine that federal regulators avoided because of abortion politics. That field has long suffered from a reputation as a "Wild West" branch of medicine in which oversight is scarce and abuses common.
"Without rules in place, you're dealing with a black box where nobody knows what's really happening," said John Fletcher, a professor emeritus of biomedical ethics at the University of Virginia in Charlottesville. "The FDA has no oversight mechanisms to look at where these embryos are coming from. You could have a runaway situation where you have embryos being created for research and the worst nightmare of liberals and conservatives coming true."
Embryonic stem cells nestle inside every human embryo and are the cells from which all kinds of adult tissue grow. In December 1998, James Thomson and colleagues at the University of Wisconsin announced that they had teased them from leftover embryos obtained from a local fertility clinic. Almost simultaneously, John Gearhart and coworkers at Johns Hopkins University in Baltimore announced that they had retrieved similar cells, called embryonic germ cells, from human fetuses.
The long-sought discoveries electrified biomedical researchers, and federally funded scientists have been clamoring to conduct experiments on the cells. But a five-year congressional ban on federal support for human embryo research has kept publicly financed researchers and ethics overseers out of the field.
That situation started to shift last year when National Institutes of Health lawyers decided that Congress's embryo research ban did not apply to most stem cell studies. NIH said it would fund the sensitive work as soon as it created pertinent ethics guidelines. But 15 months after that decision, the guidelines are still not in place.
Draft guidelines were completed on Dec. 2, proposing that scientists should use only leftover frozen embryos made for fertility treatments that are going to be discarded anyway and that have been freely donated by the mothers. But NIH officials, saying they've been swamped with comments from the public, have not sent a final version to the Department of Health and Human Services, and are not expected to until at least June. Even then, some insiders say, HHS may not release the rules until after the federal appropriations process this fall, or even after the presidential election, since many in Congress--including some with a grip on that department's purse strings--are strongly opposed to any kind of human embryo research.
In many respects, the NIH plan is moderate. It would allow federally funded scientists to conduct experiments on stem cells that others had obtained by destroying human embryos, but it would not allow them to destroy embryos themselves.
That is in contrast to the recommendations made last year by the presidentially appointed National Bioethics Advisory Commission, which concluded that federally funded scientists seeking stem cells should be allowed to destroy embryos if the mothers consent. President Clinton thanked the commission and never mentioned the report again.
Now, Congress is gearing up for a fight.
One side is led by Sen. Arlen Specter (R-Pa.), who in January introduced a bill that would essentially codify the bioethics commission's guidelines and has scheduled a hearing for April 26 at which paralyzed movie star Christopher Reeve and others will sing the praises of stem cell research.
The other side features Sen. Sam Brownback (R-Kan.), Rep. Jay Dickey (R-Ariz.) and others who say the government should not support embryo research. They want scientists to focus on stem cells obtained from adult donors, an option that many scientists believe has less medical potential.
Brownback says he can pull together enough votes to kill even NIH's more modest draft guidelines. Administration officials say he'll come up short, but they are not anxious for a congressional battle over embryos on the eve of a presidential election.
Into the void left by that stalemate, millions of dollars of private money are rushing.
With backing from Geron Corp., a California biotechnology company, as well as donations from patient groups and private benefactors, Gearhart's lab has been working furiously to move his cells toward clinical trials.
With collaborators at Hopkins, Gearhart is starting a host of animal studies to test the cells' usefulness for Parkinson's disease, Lou Gehrig's (amyotrophic lateral sclerosis, or ALS), Down syndrome, degeneration of the retina of the eye, and diseases of the pancreas and liver.
In a separate collaboration between Johns Hopkins neurologist Jeffrey Rothstein and Harvard neurobiologist Evan Snyder funded by a private nonprofit patients' group, human fetal stem cells are being injected into ALS mice in Boston. In one recent experiment, Snyder conducted muscle function studies on ALS mice with a "rotorod" machine that tests how long a mouse can stay balanced like a log roller on a rotating axle. The mice that had human stem cells injected into their spines early in the disease retained their agility much longer in life, and ultimately lived three to four times longer than the short-lived control mice.
In another Boston study led by Snyder and others, a few human stem cells injected into the spines of monkeys whose motor neurons had been destroyed developed into new motor nerve cells.
Inspired by the studies, Gearhart, Rothstein, Snyder and others met with FDA officials in February to start mapping a path to human clinical trials. ALS may be the first target for a stem cell treatment, partly because the work has shown promise and partly because ALS patients with connections to Hollywood and Wall Street have helped funnel millions of dollars in research money to the cause.
Similar research is speeding ahead elsewhere. Researchers at Menlo Park-based Geron have at least six different stem cell lines that they hope to turn into medical treatments for the brain, heart and liver, Geron President Tom Okarma told a scientific meeting in February. (Company officials contacted last week could not say how soon they might seek FDA permission to begin clinical trials because Geron is now in a "quiet period" imposed by the Securities and Exchange Commission in preparation for a public stock offering.)
In Madison, the University of Wisconsin's nonprofit Alumni Research Foundation recently created the WiCell Research Institute, a private, nonprofit laboratory that, because it receives no federal funding or equipment, is a safe haven for scientists wishing to conduct stem cell research. The institute plans to distribute Thomson's stem cells to scientists at U.S. pharmaceutical companies and elsewhere within the next six weeks.
"The requests have been numerous," said Carl Gulbrandsen, the foundation's managing director.
Gulbrandsen said the institute will insist that researchers who get the Wisconsin cells agree to certain ethical guidelines for their use, such as not using them to clone a person. Ironically, however, the cells being offered are themselves in violation of the draft NIH guidelines. Some of them were derived from fresh fertility clinic embryos, while the draft guidelines insist that only frozen embryos be used as insurance against mothers feeling rushed to make a decision to donate.
Gulbrandsen said the university has asked NIH to "grandfather" the Wisconsin cells into the guidelines. "We think we're close enough that it would be a shame not to be able to use these cells just because we haven't dotted every i and crossed every t," he said. "It's a shame, I think, that the process has been so politicized."
The FDA still has many questions about the science, including the safety of putting embryonic or fetal stem cells in people.
Among the concerns are that stem cells are quite mobile and could travel to distant reaches of the body where they may turn into the wrong type of tissue or become tumors. Also unknown is whether stem cells might trigger dangerous immune system reactions in recipients.
Many of those concerns are slated to be discussed at a July FDA meeting. But while that meeting will be open to the public, details of privately funded human stem cell experiments will be kept confidential, in keeping with FDA rules.
Moreover, say supporters of public research, the FDA does not have the authority to judge the ethics of an experiment, including consideration of the source of stem cells and whether they were obtained with proper consent.
"Unless some government oversight gets involved," Harvard's Snyder said,
"there's going to be a burgeoning of disreputable entrepreneurs preying
on vulnerable patients with cells from who knows where."