Freeing Up Stem Cell Research

Cell boom: Shown here is a colony of embryonic stem cells. Credit: NIH

Three years ago, when Rene Rejo Pera was setting up a new lab at the University of California, San Francisco (UCSF), she had to make sure she had two of everything: one microscope for her federally funded lab, for example, and one for a privately funded replica next door. Because of funding restrictions on stem-cell research ordered by President George W. Bush in 2001, this was a redundant scenario played out in labs across the country. The edict specifically limited federal funding for embryonic stem-cell research to a small number of cell lines already in existence, leaving scientists who wanted to conduct cutting-edge research in this area scrambling for private money.

Scientists are now looking forward to an end of that edict. President Barack Obama promised during his campaign to overturn the order, and most expect the action to happen soon. "The imminent change in policy will quite literally allow us to take down these walls and integrate the laboratories in a way that will make the work move much more efficiently," says Arnold Kriegstein, director of the Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

The new policy is expected to mean that scientists will have unfettered access to newer, better embryonic stem cells, which will speed the pace of research. Even without funding restrictions, however, scientists receiving government grants could not use that money to generate new lines, which requires the destruction of an embryo. Kriegstein and others hope that the change will bring a new sense of legitimacy to an often embattled field, as well as return a leadership role to the National Institutes of Health (NIH), the nation's premier biomedical funding agency, in one of the most promising areas of biomedical research. Much of the research has shifted to institutes funded by state initiatives, such as the California Institute for Regenerative Medicine, or by private donors. In addition to limiting funding, "the other reality of [the Bush] policy is all the negative publicity it has created," says Tim Kamp, codirector of the Stem Cell and Regenerative Medicine Center at the University of Wisconsin. "Frankly, I think it did greater damage than funding restrictions, [in] that it scared many researchers away."

Despite the restrictions, U.S. scientists have employed embryonic stem cells for a broad range of research. Because the cells can develop into any tissue type, scientists are coming up with ways to prod them to differentiate into brain cells, heart cells, and other cell types, both to better understand the diseases that strike these tissues and to potentially create replacement tissue for therapies. But much of the most promising research has moved overseas.

Once the restriction is lifted, labs funded by federal dollars will be allowed to use most of the estimated 600 stem-cell lines that have been created around the globe. Researchers broadly agree that the newer lines, which were derived using more refined methods, are superior to the older ones. Using only the old lines is like "being required to use Microsoft Word 1998," says Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute, in La Jolla, CA.

In addition, the earlier lines were derived using animal products, making them largely unfit for therapeutic use. "There are hundreds of embryonic stem-cell lines out there that have been made under the best conditions, and some of them are patient ready," says John Gearhart, director of the Institute for Regenerative Medicine at the University of Pennsylvania, in Philadelphia. "They have greater utility, performance, and safety than [the Bush-approved] lines."

Scientists will also be able to study cell lines that are genetically encoded for specific diseases--perhaps one of the most promising near-term uses of embryonic stem cells. (None of the Bush-approved lines have these qualities.) "One of the clear opportunities that has not been available are lines generated from embryos that carry mutations for Huntington's disease, amyotrophic lateral sclerosis (ALS), and cystic fibrosis," says Story Landis, director of the National Institute for Neurological Disorders and Stroke, in Bethesda, MD, and chair of the NIH's Stem Cell Task Force. These cells provide unprecedented access to the molecular processes underlying disease; they can be prodded to develop into the cell type affected in a specific disease, such as motor neurons in ALS, so that scientists can watch the disease unfold at a cellular level. These cells can also be used to screen new drugs.

Scientists and policy makers are still guessing as to when and how President Obama will reverse the restrictions--whether he will issue an executive order, or let Congress decide the matter. But according to White House press reports last week, the president promised the former. Prior to Obama's presidency, Congress twice passed a bill reversing the restrictions, the Stem Cell Research Enhancement Act, which Bush twice vetoed.

It's not yet clear how quickly the field will rebound from the funding limits. Many scientists were discouraged from studying embryonic stem cells during the past eight years because they couldn't secure private funds, or because they or their universities did not want to deal with the extensive accounting required. "The effect of the restrictions was to create a few centers going forward, like mine and like Harvard, Stanford, and UCSF, which had access to private and state money," says Loring. "Now there will be more room for people to get involved, but they'll be eight years behind."

The field has changed dramatically since President Bush's edict, especially in the past two years, which may make new funding freedom less significant. A newly developed technique to create stem cells--called induced pluripotent stem (iPS) cell reprogramming--does not require the destruction of human embryos, and scientists hesitant to take on embryonic stem cells have been flocking to the new approach in droves.

Researchers have been able to do many of the same experiments with these iPS cells as they have with embryonic stem cells. However, they caution that these cells have not been shown to carry all the power of embryonic cells--for example, they cannot differentiate into as many cell types. "It's very important that labs be able to do experiments with both kinds of cells side by side," says Kriegstein. "Relaxing presidential policies will make this much easier to accomplish."

One area of research that won't change with removal of the restrictions is therapeutic cloning. In therapeutic cloning (also called somatic cell nuclear transfer), scientists transplant DNA from an adult skin cell into an egg that has had its DNA removed. Unknown factors in the egg reprogram the adult DNA to resemble embryonic DNA, and, in theory, the cell begins to develop like a normal embryo. Scientists would like to create stem cells from cloned human embryos, both for research and potentially for therapy: the cells would be genetically matched to their human donors and thus could be transplanted without fear of rejection. But no one has yet accomplished this with human cells and eggs. Research that involves destruction of human embryos, which includes both cloning and derivation of new stem-cell lines, is prohibited from federal funding under the Dickey Amendment, a rider to the appropriations bills that have been passed in Congress over the past several years.

By Emily Singer