The Biological Mother Lode

By MICHAEL D. LEMONICK

For a fleeting time, a day or two at most, all things are possible for an extraordinary group of cells that form part of a newly created embryo. Known as embryonic stem cells, they have the capacity to grow into any sort of tissue the body will need--nerves, blood, heart, bone and all the rest. And then they start to do just that, abandoning their unlimited promise in order to do something useful with their lives. Scientists have long believed, however, that embryonic stem cells could be terrifically useful in their unspecialized state as well, not only as a source of information about how cells develop but also as a source of replacement for tissue damaged in a wide range of diseases.

Until now, though, isolating stem cells in their pristine state has proved difficult, and keeping them that way for further study next to impossible. That is why it is so remarkable that two independent teams, one at the University of Wisconsin in Madison, the other at Johns Hopkins, announced last week that they had both pulled it off. The Hopkins team, according to a report in the latest issue of Proceedings of the National Academy of Sciences, got stem cells to survive in a petri dish for as long as nine months.

The Wisconsin group, whose announcement appears in the current Science, went even farther. Its stem cells can evidently survive indefinitely. The researchers have also coaxed them to take the next step and differentiate into neural, gut, muscle and bone cells. "It's an important first step," says developmental biologist James Thomson, who led the Wisconsin team. National Institutes of Health director Harold Varmus pronounced the potential applications of the Wisconsin work "tremendous."

The potential controversy, however, is equally tremendous. It is illegal to use federal money for research that involves human embryos--leading both the Johns Hopkins and Wisconsin groups to seek funding from Geron Corp., a biotech firm based in Menlo Park, Calif. But staying within the letter of the law has not saved the scientists from attack. Biotechnology critic Jeremy Rifkin petitioned Congress last week to ban all privately funded research into embryonic stem cells so that there can be a "full investigation of the profound long-term social and ethical implications of the technology." Right-to-life activists chimed in as well. The stem cells were taken from potential human beings, says Judie Brown, president of the American Right to Life League. Asserts Brown: "These human beings should be protected by law."

The sources of cells, however, were not human beings in a legal sense. The Johns Hopkins researchers took theirs from fetuses that had been aborted early in pregnancy. The Wisconsin group used blastocysts, clusters of about 140 cells that develop within a week after fertilization. (They were donated by couples who had extra blastocysts left over from in-vitro fertilization.) The scientists, however, were hardly indifferent to ethical concerns. At Johns Hopkins, for example, it took nearly four years of testimony in front of scientific and ethical review panels before the work could even begin. Says team leader John Gearhart: "The potential for these cells weighed very heavily into whether we should do this or not."

That potential seems almost limitless today. In principle, stem cells could be used for a vast array of profitable--and lifesaving--therapies. They could, in theory, be coaxed into forming heart cells, for example, and injected to patch up heart muscle damaged by cardiovascular disease. They might be turned into neurons to replace brain cells destroyed by Alzheimer's. They may someday provide new pancreatic cells to pump insulin into the bloodstream of diabetics.

The list goes on to include virtually any disorder that involves the loss of normal cells: stroke, muscular dystrophy, spinal-cord injury, kidney or liver disease, blindness caused by degeneration of the retina. Stem cells could also provide drug companies with a limitless supply of normal human tissues to use in testing the toxicity of new drugs. "This is a fairly unique resource," says Johns Hopkins team leader John Gearhart, in a masterpiece of understatement.

But such applications are years away at best. At this point, it is not clear whether the isolated stem cells can produce literally any tissue in the body or can make only the few types already seen in the lab. And if it is the latter, why? If the experiment had been done in mice, the next step would have been to test the stem cells' versatility by trying to grow an entire mouse. Such an experiment would clearly have been unethical with human cells.

Another key question is whether scientists can learn to guide stem cells into specific paths of development. Although the Wisconsin group managed to get its cells to differentiate, the scientists had no control over what the cells turned into.

Answering all these questions and turning the answers into useful therapies is a daunting undertaking that could keep scores of scientists busy for years. Unfortunately, Geron's pockets are not bottomless, and the traditional source of funding is unavailable. In order to inoculate themselves against charges of violating a federal directive, the Johns Hopkins and Wisconsin scientists had to declare that no federal funds were used in their work. The Wisconsin group went so far as to set up a separate lab so federally funded equipment would not be "contaminated."

Yet pushing the research forward in a timely fashion requires the sort of support only the government can provide. "I'm convinced that there will be therapies based on these cells in my lifetime," says Wisconsin's Thomson. "But when that occurs will depend heavily on whether there is public involvement." Given the chances of overturning the funding ban in today's political climate, it is more likely to be later than earlier.

--Reported by Dick Thompson/Washington

With reporting by Dick Thompson/Washington