Stem cells partition labs

Researchers fearful of jeopardizing grants must isolate work on unapproved lines.

Published July 5, 2007

BALTIMORE - On the seventh floor of the glass and steel research building at the Johns Hopkins School of Medicine, where graduate students in lab coats and Crocs stare into microscopes, there's a little room with a locked door.

One wall is lined with isolation hoods that protect human embryonic stem cells from contamination as they're added to nutrients. They look somewhat like hotel icemakers. The other is lined with incubators, where the newly cultured cells will divide and multiply into colonies useful for research. They look like minifridges.

The little room cost almost $4-million. But when it opens later this summer, it will remain locked to Hopkins researchers who depend on grants from the National Institutes of Health, one more effort toward self-preservation under the nation's restrictive stem cell policy.

"If you're 100 percent funded by the NIH, you don't go through here," said Dr. Chi V. Dang, the school's vice dean for research. "You don't cross this threshold."

President Bush's recent veto -- for the second time -- of a bill to expand federal funding for embryonic stem cell research has been discussed mostly in ideological terms, but it has vast practical implications as well.

Only 21 embryonic stem cell lines are available for NIH funding under the president's policy, and most U.S. researchers can't tap the expanding number of private or foreign-made embryonic stem cell lines.

For major medical centers with the resources to work with those new lines, the president's strict policy requires extraordinary steps to ensure that money from NIH grants for other projects in no way supports research on the unsanctioned lines, directly or indirectly.

At the University of Minnesota, this means researchers working with unapproved stem cells use different brands of pens and different colored ice buckets than those working with NIH grants. At Children's Hospital Boston, it meant spending $2.5-million in private donations to section off a new lab for Dr. George Daley, who works with embryonic stem cells in search of cures for blood disorders, and to stock it with new equipment the hospital already had. A separate accountant was hired to manage the paperwork.

And at Johns Hopkins, where embryonic stem cells first were isolated in 1998, Dang's little lab within a lab is the latest measure the school has taken to ensure that its aggressive work with unapproved lines doesn't jeopardize the millions of dollars it gets in NIH funding.

Using $28-million from an anonymous gift that launched Hopkins' Institute for Cell Engineering, the school built and equipped labs on the sixth and seventh floors of its main research building in downtown Baltimore.

This gave all investigators the freedom to use the microscopes, centrifuges, molecular imaging machines and chemical screeners, regardless of what they're researching and with whose money. But because many get NIH grants for adult or sanctioned embryonic stem cells, Dang designed the new lab as one more safeguard.

"This will be strictly for unapproved lines," Dang said. "You can do it here, and you won't get dinged."

Rules drive up the cost

Stem cell research is about curing ailments. It's also about money.

Scientists believe stem cells, as the building blocks of life, can replace almost any cell, from insulin-producing pancreatic cells for diabetics to neurons for people with Alzheimer's disease.

Though stem cells come from many places in the body, embryonic cells appear the most malleable and the most promising. But harvesting them destroys the embryo, and opponents equate it with abortion.

This year, the National Institutes of Health will allocate about $657-million for research on stem cells, from so-called adult stem cells taken from umbilical cord blood, the placenta and some organs, as well as stem cells teased from mouse embryos.

A fraction of that, about $37-million, will be used for research on the 21 embryonic stem cell lines that meet the president's policy of having been created before Aug. 9, 2001. As many as 400 new embryonic stem cell lines have since been developed worldwide, and many offer genetic diversity and other traits that researchers say they need to explore.

"If you're going to test an idea out, the more lines you try, the more cells you try, you're going to get a more accurate readout of what's going on in the biology of these cells," said Dang, who also is a cancer researcher. "Stem cells are not all the same."

But because NIH funding is off-limits, nothing financed by federal dollars, from microscopes to incubators to test tubes, can be used on unapproved lines. Universities also must segregate the latent costs of such research, from construction of new facilities to rent and utilities to salaries.

"Every little thing is duplicated," said Daley, the Children's Hospital researcher and president of the International Society for Stem Cell Research.

"It's a major hassle and makes the science more expensive. And so I think many investigators will make a decision to either do very limited work on the set number of cell lines that are available for federal funding, or they'll forgo the research altogether."

So far, most university research centers have simply chosen to forgo it, in part because the pool of private funding for such work is relatively small.

No one tallies which of the 125 major medical schools work with unapproved stem cell lines.

The top ones are widely known, including Hopkins, Harvard, Minnesota, Wisconsin and several California schools. Tony Mazzaschi, associate vice president for research at the Association of American Medical Colleges, said more may be working with unapproved lines and just don't want the publicity.

At the University of Miami, the Diabetes Research Institute set up separate labs and accounts for scientists working with unapproved stem cells. Florida's public research centers, the University of South Florida and the University of Florida, work with stem cells, but not human embryonic stem cells.

State schools, particularly, don't advertise their stem cell work because they "worry about sanctions from state legislators," Mazzaschi said.

Keeping work separate

When Dr. Meri Firpo worked at the University of California at San Francisco, where she derived two of the approved presidential lines, the rules were evolving along with the science. The school was also one of the first institutions to be audited for how it managed its funding for approved and unapproved research.

"We had to make each decision at a university level, incrementally, for each issue as it came up: Can we use this building or this facility, or do we have to rent space?" Firpo said.

To keep funds and equipment separate, she rented a lab 3 miles from campus.

Now, as the top stem cell researcher at the University of Minnesota, Firpo and the university incorporated the rules as they designed and built the new Stem Cell Institute, a model for how to conduct NIH-sponsored research alongside work on unapproved embryonic stem cell lines.

Firpo works in a "lab within a lab," a space inside the Institute with access by key card. Researchers and technicians there use purple ice buckets; those in the main lab use red.

Those in Firpo's lab use Uni-Ball Vision pens. Those in the main lab use Pentel TKO pens.

"The bonus was that since pens are the first thing to migrate, I can tell if things ever start to move around," Firpo said.

Minnesota also created a separate system for tracking purchases, salaries and other costs of working with unapproved lines. This way, all spending can be accounted at every level - a comforting thought in the event of an audit.

"I know this sounds so nitpicky and stupid, but it's really made this transparent," Firpo said. "They send the bills for electricity for the building, cleaning, heating ... to the dean, and he can pay the bills out of different funds."

But what about intangibles, like thought? While accountants wrangle over pens and office space, some researchers say the policy hampers a core tenant of science: collaboration.

That's especially true at a place like Hopkins, where many researchers work on stem cell lines approved for NIH funding, as well as those that are not.

"What about the ideas I get from working with approved lines?" Dang asks. "Can I feed them into the work I'm doing with unapproved lines? That's something that hasn't really been thought out."

Wes Allison can be reached at allison@sptimes.com or (202) 463-0577.

Fast Facts:

Federal policy

President Bush's policy allows the National Institutes of Health to pay for research only on human embryonic stem cell colonies created before 9 p.m. on Aug. 9, 2001, the date and time Bush announced it.

Twenty-one lines meet the president's criteria, although their utility is limited because of their age and the relatively old technology used to create them. An estimated 400 lines have been created since then, through privately funded or foreign research, but they are off-limits for NIH funding.

Source: National Institutes of Health; Coalition for the Advancement of Medical Research