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Stem cells beyond federal funding embargo
POSTED 19 MARCH 2009

Stem cells: Making progress, or counting the losses?

So what did eight years of restrictions cost the field of stem cell research? We could not get a numerical answer, as we could not find a planet that was identical except for the absence of the ban, so we asked some people who should know.

"It slowed down the field," says bioethicist Alta Charo, a professor of law at University of Wisconsin-Madison and advisor to the Obama Administration. "Younger scientists entered in smaller numbers due to the relative dearth of funding. Research was made more expensive due to the requirements for strict separation of federally-purchased laboratory equipment from the equipment used for this research. The U.S. is still a leader, but only due to the depth of its pool of scientific talent, not because it has in fact led the world in supporting the work."

Embryonic stem cells in the study of Lou Gehrig's disease

The drug-treated green cord-like axons run in parallel, the others are tangled around a void.
Images: CIRM and M. Carol Marchetto, Salk Institute for Biological Studies
In amyotrophic lateral sclerosis, support cells called astrocytes seem to be killing the motor neurons. This cell system could be used to screen drugs against ALS. (Cell nuclei are blue, neurons are green.)
Left:
When astrocytes were made from mutated ES cells, they could not make a compound that protects against oxidation, and nearby motor neurons died.
Right
: In the same situation, the motor neurons survived after being treated with an anti-oxidant.

Following the Bush rules has "been very inefficient in many respects," says Alan Trounson, president of the California Institute for Regenerative Medicine, which funds an extensive portfolio of stem-cell research in California. "Trying to run research with two different rules, where the facilities, and the grants, had to be completely separate has been very complicated, very tiresome. It cost a lot in administration and auditing, trying to keep to the rules."

The Obama decision, Trounson says, "Has taken away a lot of the excess bureaucracy, and now the research will go forward in a more unrestrained way."

"I think we are tremendously behind where this should be," says Bernard Siegel, director of the Genetics Policy Institute, a group that tries to meld the needs of patients with those of researchers. Spending by the National Institutes of Health on human embryonic stem cells over the last eight years "has been a pittance, compared to what it should have been given the potential of the field. We have been on an eight-year hold..."

Siegel mentions a key objection to the 21 stem cell lines for which Bush did allow funding: These products of the first efforts to grow embryonic stem cells had been exposed to animal proteins, which could carry animal viruses and therefore were not safe for human use. In addition, Siegel says, "There are many new lines, some disease-specific lines, available to researchers, but the NIH money was not there for them. NIH has been the great engine for basic medical research in the world, so we have been going too slow on something that holds a great deal of promise."

Pie chart shows that 65, 29, and 5.9 percent of funding goes to the respective research types
Data source: Baltimore Sun
Even though embryonic stem cells are a fundamental discovery, they received only $41 million of the $698 million that the National Institutes of Health approved for stem cell research in 2008. Research with non-embryonic human stem cells got $203 million, while non-human and umbilical-cord blood stem cell research got $454 million.

Two, three, many stem cells

Assessing the cost of the ban is also complicated by the elusive nature of stem cells. These flexible cells originate in the embryo, and gradually spawn populations of mature cells that form the skin, gut, blood vessels and everything else. A group of intermediate stem cells, called adult stem cells, include those in the bone marrow that produce blood cells, persist for a lifetime. The use of adult stem cells in bone marrow transplants for treating cancer helped opponents of ES cell research argue against the need to fund embryo-derived cells.

Then, more than a year ago, scientists learned to make induced pluripotent stem (iPS) cells, which closely resemble embryonic stem cells, but have some advantages, such a dispensing with the need for embryos. Although both iPS and adult stem cells helped shift funding away from ES cell research, scientists almost unanimously insist that ES cells remain a primary driver of research. James Thomson, the discoverer of ES cells and co-discoverer of iPS cells, wrote last week, "Human-induced pluripotent stem cells -- the transformed adult cells that seem to mimic the qualities of embryonic stem cells -- would not have been possible without research on human embryonic stem cells." Embryonic stem cells, he says, remain the "gold standard" for stem cell research.

The Why Files scrounged around for an objective comparison of stem-cell progress between the United States and other nations where the ban had no effect, but the only study we found ended in 2004 (see # in the bibliography). The report showed a quick uptick of international publications compared to a flatter rise for U.S. publications in 2004, so we phoned co-author Jennifer McCormick, of the Mayo Clinic in Minnesota, but she told us "we really can't draw a strong conclusion about current trends based on the earlier study." However, she added, "I think that the Bush policy didn't help the field. When the policy took effect, human embryonic stem cell research as a new emerging area was stymied."

Getting down with diabetes

Another way to assess the cost of the eight-year restriction is to focus on a laboratory that uses stem cells. Jon Odorico, associate professor of surgery at the University of Wisconsin-Madison, uses stem cells to study diabetes, looking in particular at the formation of beta cells, which produce the hormone insulin in the pancreas. "We are using embryonic stem cells as an in vitro [in the dish] model for studying pancreas development, and the formation of beta cells," he says. "What genes and what growth factors are involved in this process? Can we construct a protocol in the culture dish, to turn embryonic stem cells into beta cells?"

These studies could shed light on how to make replacement beta cells for cell transplants that might restore the body's normal insulin production. They could also show how beta cells grow during normal human development; most studies on their development have been performed in mice, chickens, fish and frogs, Odorico says.

The image looks like a piece of dark granite covered in pale blue, green and pink lichen patches
Insulin granules are the black spots in this slice of rat beta cell. In rats and people, beta cells make insulin, the hormone that allows sugar to enter cells; lack of insulin (or failure to respond to it) constitutes diabetes.

Odorico's lab has studied several federally approved embryonic stem cell lines, but ideally he would have studied other lines as well. Comparisons are critical, Odorico explains. "If we compare stem cells from an embryo of a young couple that had no genetic history of type 2 diabetes to a stem cell line with that tendency," he says, "we can find differences in the genetic code" or in other factors that control how insulin is produced and how well beta cells survive.

Stem-cell lines from people with genetic diabetes may show abnormal beta-cell development, he adds. "They might become progenitor cells, but not beta cells, or not even become progenitor cells. Or they could become beta cells but die off readily." But because federal funding regulations have prevented Odorico's lab from establishing new ES cell lines and from acquiring non-approved lines from other labs, those critical comparisons have not been done.

Doing these types of in-the-dish lab studies can advance diabetes research, he adds, and ultimately lead to either stem cell therapies or drug treatments for diabetes.

So how much did the ban hurt researchers who want to use embryonic stem cells? "It's hard to quantify," says Odorico. "Would there be more scientists doing stem cell research in the absence of the Bush ban? Certainly. The field would have grown even faster, and more broadly, and perhaps there would have been more incentive for commercialization. The Bush ruling definitely delayed and inhibited progress."

So where do we go from here?
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Terry Devitt, editor; Nathan Hebert, project assistant; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive

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