Stem Cell Limits Have Scientists Seeing Double

For biologist Meri Firpo, the controversy over human embryonic stem cells boils down to pens.

In one of her laboratories -- the one that gets government money to study federally approved stem cells -- researchers are required to use Paper Mate Flexgrips.

Just across the hall is a nearly identical laboratory set up with private funds so she can study new embryonic stem cell lines that do not have President Bush’s seal of approval. Firpo requires lab workers there to use Uni-balls to make sure no federally funded pen finds its way into forbidden territory.

It’s an admittedly peculiar situation, but Firpo, a professor at the University of Minnesota, said she was not taking any chances. A willful violation of federal policy could make her liable for criminal and civil penalties. Even a mistake might imperil federal grants for her lab -- and for the rest of the university.

Bush’s embryonic stem cell policy, which now restricts federal support to research involving about 20 cell lines, has created a logistical nightmare for science.

Researchers who study both federally approved and unapproved stem cells have had to buy duplicate equipment to conduct their experiments, then set up elaborate systems to keep their work completely separate.

Some scientists say the cumbersome dual system -- reaffirmed last month when Bush vetoed a bipartisan bill that would have expanded funding to more than 100 newer cell lines -- puts U.S. researchers at a disadvantage.

“This is a bunch of compliance red tape that is a real pain in the neck,” said Dr. John Boockvar, who heads Cornell University’s Neurosurgery Laboratory for Translational Stem Cell Research. “It’s hard enough to do successful research without having to worry about all this stuff.”

So far, federal funding agencies have yet to redress anyone for violating their rules. But the fear that they would is palpable, because universities rely on the federal government for nearly two-thirds of their overall research budgets.

Don Ralbovsky, a spokesman for the National Institutes of Health, which bankrolls the bulk of federal stem cell funding, said the government was willing to be flexible.

If a researcher inadvertently mixes money, “we would work with them to rectify the situation and make whatever restitution is necessary,” he said.

Those words offer little comfort to developmental biologist Susan Fisher of UC San Francisco.

Fisher was conducting research in a converted pediatric clinic in 2002 when a winter storm knocked out the power, shutting down the freezers that housed the stem cell lines her group had spent two years cultivating.

The makeshift lab had no backup power. Her freezer at home wasn’t cold enough. She considered sending the precious cell lines to colleagues with industrial-strength freezers, but all their labs were federally funded.

Her cells melted into puddles.

“I never calculated the manpower hours lost, but it was huge,” Fisher said.

The federal stem cell funding policy was created in August 2001, when Bush offered what seemed like a deft compromise to a frustratingly divisive issue.

For the first time, he offered stem cell scientists a chance at federal research funds -- a pool of money that includes more than $20 billion a year from the NIH and $5 billion a year from the National Science Foundation.

But he also had to appease social conservatives, who oppose work on human embryonic stem cells because they cannot be harvested without sacrificing days-old embryos. Each embryo is a life, they say, and to destroy one is tantamount to murder.

To ensure that taxpayers would not pay for research that destroys more embryos, he restricted federal funds to 78 existing cell lines.

Many scientists, physicians and patients saw the arrangement as a way to press ahead with their efforts to understand the mysteries of embryonic stem cells, which have the ability to become any kind of cell in the body. Learning to manipulate the cells might produce one of the biggest revolutions in medicine, leading to therapies for such intractable diseases as Alzheimer’s, Parkinson’s and juvenile diabetes.

“I thought it was a good policy because all of the lines that were available were eligible,” said Larry Goldstein, a professor of cellular and molecular medicine at UC San Diego.

“Five years later,” he said, “things have changed.”

Out of the 78 so-called presidential cell lines, researchers later found that about 20 were usable.

That was too limited to represent the variety of medical disorders and the genetic diversity of patients. As some of the lines aged, they acquired chromosomal abnormalities and other mutations that made them difficult to work with. Because the lines had been cultured with animal products, many physicians worried they could never be used for human therapies.

A solution is to derive fresh cell lines. For some scientists, there is only one way to go about that.

MIT geneticist Richard Young and his colleagues at the Whitehead Institute for Biomedical Research in Cambridge, Mass., are putting together a new laboratory with a $52,000 fluorescence microscope, two $7,500 incubators, a $6,500 tabletop centrifuge and an annual research budget of more than $1 million.

Much of it duplicates his existing lab. “We have to do it,” Young said. Otherwise, “we will lose our edge.”

At the University of Minnesota, Firpo installed a key-card security system for her private laboratory to keep out researchers who are funded entirely by Uncle Sam.

UCLA’s new Institute for Stem Cell Biology and Medicine has decided to pursue a different tack, using cost accounting to allocate federal and private dollars in proportion to the amount of time scientists spend on presidential and unapproved cells.

“In an ideal world, stem cell work will become integrated into all basic research,” said Rob DuWors, the institute’s deputy director for finance and administration. “Does that mean anyone doing any work with any unapproved stem cell line is going to have to be in a separate building? I just don’t see that being viable.”

But that delicate accounting dance makes some researchers queasy.

“You can imagine that someone wishing to cause you great trouble could do so if they could find in your accounting any evidence that you happened to commingle funds,” MIT’s Young said.

Some of the scenarios scientists are contemplating seem flat-out ridiculous given the collaborative nature of research.

If privately funded students make a discovery on an unapproved cell line, can they share that data with those funded by the NIH? If a privately funded researcher extracts proteins or DNA from an unapproved cell line, can they be analyzed with federal money?

“We have to hire lawyers to give us opinions on this,” Young said.

Goldstein of UC San Diego was so befuddled that he sent a list of questions to the NIH in November 2004. He is still waiting for definitive answers.

“It is just obscene that the government establishes a policy that not only restricts our ability to do valuable medical research, but then doesn’t even help us interpret the policy in a way that allows us to stick to it,” he said. “Everyone is making judgment calls.”

Ralbovsky, the NIH spokesman, said the agency tried to be “as helpful as possible,” but he acknowledged that there were many gray areas with no simple answers.

The ambiguity has left scientists in constant fear of tripping up.

Jeanne Loring, co-director of the stem cell lab at the Burnham Institute for Biomedical Research in La Jolla, is so wary of making a mistake that she designed homemade labels for her incubators, stainless-steel biosafety hoods and other equipment.

Items that she called “kosher” to use with any cell lines bear stickers depicting a cluster of cells surrounded by a green circle. Other stickers, for equipment paid for by the government, show cells in a red circle with a slash through it.

Loring said she hadn’t used any of the red stickers, “but they’re in the drawer in case we ever get any NIH-funded equipment.”