In the last week, two parallel realities have emerged in the field of stem cell research. One is that there are far fewer cell lines than policy-makers had believed. The second is that for scientists, there are not nearly enough.

The government has quietly revised its Human Embryonic Stem Cell Registry to reflect the reality that there are only nine viable cell collections available for medical research, not the dozens that the Bush administration initially claimed.

Meanwhile, Stanford University scientists have launched plans to use private money to create more stem cells, including some through cloning, because they say research in the promising field is too limited by what can be done with federal funding using cells on the registry now.

"If it had nine or 99, they will not represent what we need to have for the next step," said Irving Weissman, the Stanford biologist who will lead the university's new stem cell institute.

He said he believes scientists are morally obligated to pursue the research and not let politics get in the way, and he said he was glad that his state, California, recently passed a law encouraging the research.

Embryonic stem cells are primitive master cells that form all the tissues of the body. They were first isolated and grown in the lab in 1998 by University of Wisconsin-Madison biologist James Thomson, and two of his collections, called cell lines, are among the nine on the federal registry.

Scientists say the cells have unique potential to treat some diseases someday. But they believe the cells are even more important as a tool for studying diseases at the most fundamental level, in a way never possible before, which will lead to better ways to prevent and treat illness.

The cells are controversial because embryos must be destroyed to get them. On Aug. 9, 2001, President Bush said he'd allow federal money to be used for research only on stem cells that came from embryos destroyed as of that date.

Registry began with 78

The National Institutes of Health later published a registry listing 78 such cell lines. Scientists and even many of the companies and research institutions holding them disputed the number, saying many never would become viable cell lines.

"They're frozen cells, or they've died, or when they grew them out they weren't stem cells," or were in countries like India that won't allow exports to other researchers, said Paul Berg, a Nobel laureate at Stanford. The viable ones "are all of a very limited genetic diversity," he said. "If we're ever going to explore and get the full benefit of stem cells, we need more cell lines."

James Battey, a biologist who heads a new stem cell task force of science advisers at the NIH, said the registry was pared down in late November to acknowledge the cell lines currently available.

"It's a recognition that it's not clear how many of those ultimately will be distribution-quality cell lines," Battey said. If more cell lines develop from the original 78 destroyed embryos, they could go on the registry, he said.

But Battey repeated the administration's belief that those are enough for now, because so much basic research needs to be done.

"No one has been able to show me an experiment . . . that they couldn't do with existing cell lines," he said.

Center gets kick start

Weissman says he has many such experiments.

He will lead the Institute for Cancer/Stem Cell Biology and Medicine that Stanford is forming with $12 million in seed money from an anonymous donor. A chief goal is to establish a library of stem cell collections for various diseases, from breast cancer to Lou Gehrig's, for research.

Weissman said he doesn't envision creating new stem cell lines by destroying leftover embryos from fertility clinics, which is how the existing stem cell lines have been obtained.

But he does think that at some point, the research will necessitate what many call cloning: transferring a nucleus from an adult cell, such as a breast cancer cell, into another cell and making more copies of it. The nucleus is what contains a cell's genes.

In animal cloning, the adult cell's nucleus is transferred into an egg whose nucleus has been removed. It's allowed to develop for a few days to a stage where it produces stem cells, which would be removed to allow research on breast cancer or whatever disease the adult cell had.

Abortion opponents object to this because they say embryos are being created and destroyed. A second cloning technique that Australian researchers are trying, which Weissman says Stanford may attempt, isn't as objectionable to them.

Instead of an egg, the adult cell is fused with an existing stem cell and then grown into a cell line to study that disease. This results in cells with four times the normal number of chromosomes and may or may not be as useful or viable for research, Weissman said.

"We want to find the best way to make (stem) cells for research," and will consider all methods, he said.

Argument of semantics

His announcement last Wednesday ignited consternation and confusion because he and Stanford insisted they were not "cloning embryos" through such research. The argument largely boiled down to semantics.

Weissman isn't proposing to do reproductive cloning, in which embryos are implanted into a womb with the goal of producing offspring. He's also not doing "therapeutic cloning," because he's not proposing to clone stem cells that would be given to a patient as a treatment.

"It will never go into a human being," he said of the cells he plans to create.

But Stanford's plan caused a huge stir "because it has the 'c' word in it," said Kevin Wilson, director of public policy for American Society for Cell Biology, an association of 10,000 scientists worldwide who do basic biomedical research.

"Everyone thinks when they hear the 'c' word, 'creating babies.' Stanford is not going to create people, but that does not mean they're not going to do what is referred to as cloning," Wilson said. "It is very critical that research in these areas be conducted."

Weissman said his intent is "to open up a really important and enabling technology and not be blocked in a whole range of political considerations."

"We have no idea how ALS (Lou Gehrig's disease) or adult-onset diabetes or cardiovascular diseases actually happen. We know some of the genes involved. It would be the most incredible and important set of tools to have human cells that make all the kinds of cells" and use those to study diseases, he said.

In Lou Gehrig's disease, for instance, at least 10 genes are suspected of playing a role, even more in diseases such as breast or prostate cancer. Having a stem cell line from a patient with that disease would let a researcher say, "Let's fix one gene at a time and see what's important," Weissman said.

John Gearhart, a stem cell researcher at Johns Hopkins University, said Stanford's plan "is right on target."

"The real value of stem cells deals with the knowledge we're going to get out of them" to understand diseases, Gearhart said. "The value of this is going to be far more downstream than devising therapies," though the public is clamoring for treatments because there are so many diseases that can't be treated now, he said.

Gearhart also complained at the pace of research in the United States, while countries like Canada and the United Kingdom are spending great amounts of money on stem cell research for its economic and scientific benefits.

"They have infused a tremendous amount of money into this based on economics, not just science. And you look here and say, 'Oh, my gosh,' " he said.

Berg went further, and said he believes the Bush administration is deliberately slowing the pace of stem cell research by bogging it in red tape.

"I think it's scandalous how little has actually been promoted by the NIH. It's very hard to escape the conclusion that this has been put on a very slow track to please the White House," he said.

Battey said that was untrue.

"I think we have bent over backward to help the suppliers, some in other countries, to obtain NIH funding" and get stem cells to work on, he said.

"But we can't just hand them a check" without the normal review process to ensure grants are for solid research plans, he said.

So far, about a dozen administrative and eight direct research grants have been awarded since the president's announcement in August 2001. Battey said the acceptance rate is about the same as other NIH grant applications.

Which only goes to show how few scientists are willing to risk a career path on research their government isn't encouraging, Gearhart and Berg said.

"If I were a young scientist, I would think very hard about whether I would want to get involved in that mess," Berg said.