And What About The Science?

By JEFFREY KLUGER AND MICHAEL D. LEMONICK

If President Bush hoped that his decision last week to permit limited federal funding of embryonic stem-cell research would quiet the ferocious debate surrounding the issue, it was a hope that was quickly dashed. Since his announcement, advocates on both sides have continued to find plenty to argue about--whether there are really 60 existing cell lines on which the President would allow research; whether those lines would be sufficient to yield real results; whether the restrictive rules will simply drive U.S. stem-cell researchers to other countries where they can do their work with less government interference.

But nearly everyone agrees on one thing: stem cells, the unspecialized cells the body uses as raw material for tissues and organs, have the potential to treat an astonishing range of ills, including Parkinson's disease, diabetes, Alzheimer's and spinal-cord injuries. After Bush's decision, the question becomes whether they'll ever get a fair chance.

To most people, the idea of researchers dipping freely into an eternally regenerating, federally bankrolled pool of 60 stem-cell lines sounds pretty good, and that's just the way the President wanted it. "Research on these 60 lines could...lead to breakthrough therapies," Bush said. Maybe--provided scientists can get hold of them.

It was the National Institutes of Health that arrived at the 60 figure, conducting a worldwide survey of labs to determine which ones had viable cell lines already in inventory. As recently as last month, the NIH put the figure at just 30, but after what a senior Administration official described as an "arduous process" of searching, the number doubled.

The day after Bush's speech, the Administration had boosted the figure even higher, to 65. And though the White House originally reported that only half a dozen of them were derived in U.S. labs, that number too was revised upward--to 30. Whatever the actual figure, no one denies that many of the cell lines were developed by private companies that protect creations of this kind with a seawall of patents. "It is very possible that they will either not be available or available at exorbitant prices with all sorts of legal clauses attached," says Yale cell biologist Dr. Diane Krause. Says Dalton Dietrich, scientific director of the Miami Project to Cure Paralysis: "That's what all the scientists are asking this morning--how am I going to get my hands on these cells?"

The White House insists that procedures are in place to deal with just this concern--in the form of so-called material transfer agreements, under which the NIH will negotiate with patent holders for access to their cell lines. "Obviously, in any area of medical or scientific research," says the Administration official, "there are companies that get out in front of the technology, and they get the patents."

In other areas of research, however, the door hasn't been closed to latecomers the way it has with stem cells, and that has the scientific community worried. In order to maximize the medical payoff from stem-cell research, researchers prefer to work with the most robust population of cell lines possible. No one knows, after all, if some lines are more viable than others and if some lend themselves to many uses while others to only a few. If too many of the lines dead-end or die off, research could stagnate. "Some stem-cell uses," says Krause, "will require diversity greater than 60 cell lines."

Here, too, the Administration is sanguine, pointing out that the wide range of countries from which the available cell lines hail--including India, Israel, Singapore and Australia--helps ensure that they will be as diverse as possible. Some researchers even insist that the precise number of cell lines isn't important at all because none of them will actually wind up in the body. At this early stage, investigators aren't so much developing cures as creating research and manufacturing techniques. For that, the specific cell lines aren't important. "This will enable the biomedical community to iron out the molecular biology of these cells," says Dr. Thomas Okarma, CEO of the biotech firm Geron, which finances stem-cell pioneer James Thomson as well as John Gearhart, "and that doesn't turn on one cell line vs. another."

Other people are troubled not by what the Bush ruling may do to the science but by what it may do to America's standing in the world. The U.S. was embarrassed once this summer when stem-cell researcher Roger Pederson of the University of California, San Francisco--fed up with all the hand-wringing and rulemaking--was seduced overseas by Cambridge University in England. This, of course, may be just an isolated defection rather than the start of a national brain drain. "I'm not packing," quips Thomson, who pronounced himself pleased that the feds would finally make some money available. But in the wake of Bush's decision, other countries may certainly be tempted to bid for more of America's best and brightest. "Overall," says Chris Higgins, director of the Medical Research Council Clinical Sciences Centre in London, "[the decision] adds to a general uncertainty as to where research can go in the U.S."

There are, to be sure, ways around the federal rules. Nothing prevents scientists who are working with forbidden stem cells from talking to--and sharing information with--those working with approved lines. And when scientists publish their work, anyone can read it. Institutions that receive federal funds are not absolutely limited in the work they can do as long as work that falls outside the White House ban is conducted independently, with no commingling of funds or facilities or--more important--cell lines.

But even if the research proceeds apace, can stem cells ever live up to their promise? On this question, it's the science of the thing that matters, not the politics, and the science is uncertain. Investigators have already made significant advances in stem-cell research--the latest being the announcement from researchers at the Israel Institute of Technology (Technion) that they'd used a batch of embryonic stem cells to grow heart cells that actually beat and insulin-producing cells that mimic those in the pancreas. But there are plenty of steps between these advances and actual treatments--and any or all of them could pose difficulties. Says Dr. Karl Skorecki, director of Technion's Rappaport Research Institute: "We are at the beginning of a long process."

The first major hurdle is that while embryonic stem cells can develop into just about any type of tissue, scientists have little control over which one. Both the insulin-producing cells and heart cells, for example, came about by spontaneous differentiation. Scientists had to let the cells grow on their own, then pick out the ones they wanted.

But creating the appropriate cells is just part of the problem. Scientists then have to ensure that the new cells can survive in a host and do the job they're supposed to do. Dr. Lior Gepstein, leader of the team that developed the heart cells, has doubts. "If they stay in the damaged area and don't combine with the other heart tissue, they won't contract simultaneously, and they won't do any good."

Preliminary research in this area has yielded mixed results. When primitive cells are injected into rats with spinal-cord injuries, reports Dietrich, the animals' motor function frequently improves. But if you look at the rats' spinal cords at the end of the experiment, you don't see a big increase in the number of nerve cells or connections per cell. One theory about what's going on: the injected stem cells are releasing growth-promoting factors that may help the nerve cells that were already there reroute signals around the injury. Unfortunately, they may also be releasing chemicals that prevent the repair from being complete. And these are just animal experiments. Researchers will almost certainly face a whole new set of obstacles when they begin experiments on human subjects.

So given the tortuous road to stem-cell therapy, how long will patients have to wait? For some areas of research, things could move quickly, with scientists churning out lab-grown cells within a year or two. But moving into animal models and then human trials could take much longer. "There is no reason to think that this will happen overnight," says Dr. Christopher Saudek, president of the American Diabetes Association.

While research will now move faster than it would have if Bush had banned stem-cell work outright, it will also move more slowly than it would have if he had approved unrestricted funding. As the President himself allowed, there's no telling whether stem cells will be the panacea some people say. When the answers do start to come, they could be far in the future--and far beyond U.S. shores.

--Reported by David Bjerklie and Alice Park/New York, Anthee Carassava/London and John Dickerson/Washington

With reporting by David Bjerklie and Alice Park/New York, Anthee Carassava/London and John Dickerson/Washington