Curtailing embryonic stem cell research would also hurt iPS cell research, Stanford expert finds

(Press-News.org) STANFORD, Calif. — Any legislation that slows human embryonic stem cell research is likely to also seriously harm the study of induced pluripotent stem cells, according to a new study by researchers at the Stanford University School of Medicine, the Mayo Clinic and the University of Michigan.

The finding strongly refutes the idea that embryonic stem cell research can be abandoned in favor of the less-controversial iPS cells, which are derived from adult human tissue.

"If federal funding stops for human embryonic stem cell research, it would have a serious negative impact on iPS cell research," said Stanford bioethicist Christopher Scott, citing a "false dichotomy" between the cell types. "We may never be able to choose between iPS and ES cell research because we don't know which type of cell will be best for eventual therapies."

Scott, who directs Stanford's Stem Cells in Society Program, is the first author of the study, which compared the patterns of scientific publication on human embryonic and induced pluripotent stem cells. The study will be published in the June 10 issue of Cell.

The researchers also concluded that human embryonic stem cell research does not siphon federal funding away from studies of iPS cells, as has been claimed by the two plaintiffs in an ongoing Washington, D.C., district court case under consideration by Judge Royce Lamberth. Instead, studies of the two types of stem cells are likely to occur in tandem as established embryonic stem cell researchers rush to buffer themselves against a possible loss of federal funding.

"We're finding that scientific decisions are being made not because of science, but in response to other constraints, such as which cell types qualify for federal funding, how many lines are available and which can be obtained quickly and easily," said Scott.

As a result, the fields have become so tightly intertwined as to be inseparable; any loss of funding for these researchers will negatively impact all the work in their labs, including iPS cell research, Scott and his colleagues conclude.

Unlike embryonic stem cells, which are derived from human embryos, iPS cells can be created from adult tissue such as skin cells. They look and act like embryonic stem cells, but recent research has suggested that there are significant differences between the two cell types that may affect how they can be used for research and eventual human therapies.

In 2001, then-President George W. Bush restricted the use of federal funds to research on human embryonic stem cell lines derived before Aug. 9 of that year; in March 2009, President Barack Obama reversed that decision to allow research on many more cell lines. However, the legality of federal funding for human embryonic stem cell research is now being considered in the ongoing district court case filed in August 2010.

Scott and his colleagues, including senior author Jason Owen-Smith, PhD, associate professor of sociology and of organizational studies at the University of Michigan, analyzed more than 2,000 scientific papers published between 2007, when iPS cells were first reported, and 2010. They compared how many papers described research using exclusively human ES cells, human iPS cells, or both ES and iPS cells.

"It's always really interesting to look more closely at things that appear in the popular press," said Scott. "We've been hearing that, since we now have iPS cells, we don't need to continue embryonic stem cell research. There's a perception that iPS cells are 'democratizing' the field because they are fairly straightforward to work with from a technical point of view."

The analysis of published papers tells a different story. Scott, Owen-Smith and their colleagues found that the iPS field is dominated by well-established, senior hES cell researchers. Many of these researchers are publishing studies that directly compare hES cells with iPS cells, rather than focusing exclusively on one cell type.

"Although we did see a very rapid uptake of iPS cell technology during the first three years, we didn't find many new researchers moving into the field," said Scott. "The scientists who are adopting iPS quickly are the usual suspects. The old guard is working furiously to develop new iPS cell lines."

The researchers found that the original two papers in 2007 describing the creation of iPS cells had blossomed to 158 papers focused on iPS cells in 2010. In contrast, human embryonic stem cell technology was adopted much more slowly, from the first paper in 1999 to just 12 papers in 2001. Although the prior hES cell research made the adoption of iPS cell research easier, Scott and his colleagues attribute the difference in uptake of technologies to be primarily policy-driven, as researchers increasingly began to look for alternatives to the politically controversial hES cells.

However, stem cell scientists are not abandoning hES cells in favor of iPS cells. In 2008, only three of the 15 iPS cell papers (5 percent) published also reported hES cell results; in 2010, 98 of the 158 iPS cell papers (about 26 percent) did so.

"The incentives to use both types of cell in comparative studies are high because the science behind human iPS cells is still in its infancy," Owen-Smith said. "As a result, induced pluripotent stem cells do not offer an easy solution to the difficult ethical questions surrounding embryonic stem cell research."

Scott and his colleagues also directly polled stem cell researchers at the 2010 annual meeting of the International Society for Stem Cell Research, which was held in San Francisco, as to their choice of cell lines, and compared patterns of collaboration in the iPS and hES cell fields. They found that, between 2008 and 2009, 55 senior authors (those listed as last authors) published papers using both hES and iPS cells. Only 14 of the senior authors published papers using iPS cells alone. The finding suggests that iPS cell technology has not been as widely disseminated as may have been expected and that senior researchers vulnerable to legislative changes affecting ES cell research continue to dominate the field.

"The deeper implications of a federal ban or restrictions on hES cell research are largely missing from the policy discussion surrounding the Lamberth decision," they write. "We now have clear evidence showing the real possibility of collateral damage caused by ill-conceived and politically motivated policy prescriptions. Restrictions, regulatory uncertainty and spurious court decisions have undoubtedly retarded progress in the pluripotent stem cell field. Now, an entirely new technology, forged out of the crucible of political controversy, stands at risk."

### The other Stanford researchers involved in the study was postdoctoral scholar Mindy DeRouen, PhD.

The research was supported by the National Science Foundation, the National Institutes of Health and the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

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