December 1, 2008
An About-Face on Stem Cells
New Federal Grants, Less Red Tape Likely with Reversal of Bush Ban
By Frank D. Roylance
One of Barack Obama's first acts as president is expected to be a reversal of the Bush administration's restrictions on federal funding for research on human embryonic stem cells.
Maryland scientists say that's good news because it will uncork the nation's largest source of funding for promising medical research using hundreds of new cell lines, including many offering clues to the nature of genetically based diseases. Those cells are now off-limits for federal grants.
"Taking the largest funder off the table had an impact. Putting it back will certainly have a positive impact," said Dr. Paul Fishman, director of the Alzheimer's Center at the University of Maryland Medical Center.
Researchers and their institutions are also hopeful that lifting the Bush administration's ban would end a logistical nightmare. Fear of violating the federal edict forced researchers to keep everything from pipettes to buildings paid for with federal dollars separate from anything and anyone involved with stem cell lines not approved for federal funding.
"It's going to make a huge difference," said Dr. Chi Dang, vice dean for research at the Johns Hopkins University 's Institute for Cell Engineering. "Especially if I'm an investigator working on both types of cell lines, I have to be very careful. ... It's been a nightmare for some institutions."
But no one expects any funding floodgates to open. Celebration in Maryland research labs has been tempered by an awareness that the research budget of the National Institutes of Health has been essentially flat since 2003.
Until the president and Congress provide more money, stem cell researchers will have to elbow other investigators aside to win more of the available NIH money, said Story Landis, who heads the NIH Stem Cell Task Force. "We would increase funding as appropriate given the quality of the science in those proposals," she said. But until Jan. 20, she stressed, the Bush policies remain in force.
Scientists believe human stem cells hold medical promise because they are able to transform themselves, with proper prodding, into virtually any type of tissue.
Cultured in a lab, they could grow to form new skin, bone or other body tissues to repair the donor's own traumatic injuries. Or, injected into the body they could replace faulty tissues responsible for such diseases as Parkinson's, Alzheimer's or diabetes.
Stem cells derived from "adult" tissues, such as skin or umbilical cord blood, have not been controversial. They've shown some promise and are eligible for federal funds.
But the derivation of stem cells from very young human embryos has drawn objections from many who believe the resulting destruction of the embryos is immoral. For some, it makes no difference that the embryos - created during in vitro reproduction purposes but no longer needed - were to be thrown away.
Those concerns led to the restrictions on federal funding that Obama has pledged to ease while retaining what his campaign described as "high ethical standards" for such research.
Until the NIH develops its own ethical rules, all work with embryos must comply with professional and institutional guidelines ensuring, among other things, that embryo donors gave informed consent and received no financial incentives.
Despite its promise, human embryonic stem cell research has received relatively modest federal funding. Of $698 million approved by NIH for all stem cell research this year, only $41 million has gone to work with human embryonic stem cells, limited to just 21 approved cell lines.
By comparison, research using nonembryonic human stem cells received $203 million in NIH funding this year. The balance goes to nonhuman and cord blood stem cell research.
"The greatest scientific engine in the history of man is the NIH, with a $28 billion yearly budget. And for eight years it has been largely on the sidelines in one of the most promising areas" of medical research, said Bernard Siegel of the Florida-based Genetics Policy Institute, an advocacy organization promoting stem cell research.
A number of states, among them New Jersey , Wisconsin , Massachusetts , Illinois and New York , have moved into the breach with their own tax dollars. The largest has been California , approving $3 billion over 10 years. Maryland 's Stem Cell Initiative plans to spend $219 million over 10 years.
Some critics of embryonic stem cell research argue that successes with adult stem cells have curbed the need for work with embryonic cells. But scientists say it's too soon to reach that conclusion.
"I think we're going to see different forms of stem cells used for different clinical purposes," Fishman said. "It's scientifically naive to think we'll end up with one strategy and one type of cell."
But before researchers can benefit from new federal dollars, the Obama administration will have to clear at least two barriers to federal funding.
The simplest to reverse will be President George W. Bush's policy statement, in a speech on Aug. 9, 2001, that limited federal funds to human cell lines already in use at the time of his pronouncement - that is, whose source embryos had already been destroyed.
Although the administration counted about 60 cell lines in that category at the time, scientists say only 21 have proved useful. Of those, some don't grow well in labs; others have unwanted genetic anomalies, viruses or animal components. And most were derived from white people, so any discoveries they yield might not apply across the population.
Researchers working without federal dollars have since developed more than 400 human embryonic stem cell lines, according to one count published two years ago. But none is eligible for federal funding, at least not until Obama says otherwise.
"Most people think the Bush policy was an executive order. It was just a speech," said Amy Comstock Rick, president of the Washington-based Coalition for the Advancement of Medical Research, comprising patient organizations, universities, scientific societies and foundations advocating for breakthrough medical research. "All Obama will need to do is simply rescind that with his presidential authority."
But there is another brake on federal funding the Obama administration will need to address. It's called the Dickey-Wicker amendment, passed by the Republican-controlled Congress in 1995.
The amendment bars the use of federal funds for research in which embryos are destroyed, discarded or "knowingly subjected to risk of injury or death greater than that allowed for fetuses in utero."
That effectively eliminated federal funding for the creation of new cell lines, because the process ordinarily destroys the embryo.
"The Dickey-Wicker amendment has ... slowed the progress of the field for all these years," said Siegel, at the Genetics Policy Institute. Obama should seek its repeal, he said, but "we don't expect that to happen overnight. What we do expect very soon is an executive order lifting President Bush's restrictions."
The prospect of a less restrictive and bureaucratically tangled research environment has delighted Maryland researchers.
"The Bush ban has really, dramatically suppressed work with new [embryonic stem cell] lines," said Fishman, of the University of Maryland . The "overwhelming" majority of stem cell research at his institution "does not involve new lines of embryonic stem cells."
"This is something we've been interested in expanding with the help of Maryland 's Stem Cell Initiative," he said, while also planning for the day when federal restrictions would be lifted.
If a major new NIH funding became available, he said, "you would probably see a lot of new investigators entering that field."
The prospect of new money and less red tape has delighted scientists at Hopkins , too, Dang said. "Some labs were celebrating after the election. ... People now won't be limited to 20 or so approved cell lines. They can write a grant proposal to do 50 cell lines rather than limit the science arbitrarily. People can be more creative, more adventurous to really design experiments the right way."
Hopkins ' Institute for Cell Engineering - using state and private funds and anticipating that federal policies would change - has dedicated up to 40,000 square feet of lab space to accommodate added stem cell research, Dang said.
Almost as welcome is the prospect of tearing down the bureaucratic wall between cell lines derived before and after Bush's 2001 speech.
While Hopkins managed to keep federal and other research separated by restricting them to separate floors, other institutions have felt compelled to go further.
For example, to protect its NIH funding, the University of California- San Francisco spent $6 million several years ago to strip bare a perfectly good lab that had been built with federal funds and rebuild it with private dollars so it could be used for work with new cell lines not eligible for federal funding.
The Bush ban and the red tape that came with it "has made the whole field a little bit more nervous, and deterred some young researchers from getting into it because it was viewed as a risky career path," said Rick, of CAMR.
"We've had issues at Hopkins ," Dang said. "We've lost investigators to California with their $3 billion [state] commitment to this effort."
Less experienced researchers "have been kind of lured away to Europe ," he said.
An infusion of NIH dollars for work with new embryonic stem cell lines should also excite interest among private-sector labs seeking to collaborate with academic labs in the development of new therapeutic products, Fishman said.
"I think that will open the door for more of that collaboration," he said. "At least for the limited amount of NIH resources available, this research will be able to compete."