Back in the Bay Area: Sabbatical draws stem cell expert Pedersen to Stanford

Christopher Vaughan

Stem cell scientist Roger Pedersen has been working in England since leaving UCSF in 2001.

Roger Pedersen— the stem cell researcher who famously left UC-San Francisco in 2001, citing an increasingly unfriendly climate for stem cell research in the United States — has come to Stanford's Institute for Stem Cell Biology and Regenerative Medicine for a one-year sabbatical.

Pedersen's 2001 departure for the U.K., and the reasons for it, became part of a clarion call for greater non-federal support for stem cell research. That movement culminated in the 2004 passage of Proposition 71 and the establishment of the California Institute for Regenerative Medicine.

While at Stanford as a Siebel Scholar, Pedersen will conduct research, teach and collaborate with other researchers as part of his leave from the University of Cambridge, where he is director of research in the Anne McLaren Laboratory for Regenerative Medicine.

Pedersen transferred his research from UCSF to Cambridge just over a decade ago as the U.S. government was clamping down on federal funding for embryonic stem cell research. Although Pedersen actually decided to leave before then-President George W. Bush announced a controversial policy that limited federal funding for embryonic stem cell research to a small number of existing cell lines, there was already a ban on federal funding for research on human embryos. Pedersen and UCSF halted some research in his lab because ambiguities over National Institutes of Health policies made it unclear whether federal funding of overhead costs required that even non-federally funded embryo research be done "off campus."

In the fall of 2000, Pedersen had taken a short sabbatical at Cambridge, which gave him the chance to observe the U.K. parliamentary debate over embryonic stem cell research. "It went the opposite way to our debate," he said, of the British lawmakers' decision to allow all human embryo research "for treatment of serious diseases."

Pedersen told one of the debaters, Cambridge's Clinical School head, Sir Keith Peters, to let him know if there was anything he could do to help, to which Peters replied, "You could come here."

"I thought he was joking, and in any case, I was looking forward to a positive outcome from my application to NIH for stem cell research under the funding policies developed by Harold Varmus during the Clinton administration," Pederson recalled. "But shortly after I got back to UCSF from Cambridge in early 2001, I had a phone call from NIH headquarters to say that they were terminating my application. I later learned that this reflected NIH's imposition of the newly elected Bush administration policies for stem cell funding. That's when I began thinking seriously about moving to England."

By that time, all of Pedersen's stem cell research funding was coming from a University of California BioStar grant that matched a contribution by the biotechnology company Geron. While this provided adequate funding, that fact that it depended on a single funding source had him worried. "I was concerned that Geron might lose interest in funding our project because we couldn't do the one thing that they really wanted us to do then, which was to create ES cells from cloned human embryos," Pedersen said. "An interesting side note is that no one has still done that to this day."

The situation seemed to Pedersen much like that of a business with one customer, something he knew all too well. "My father established a sawmill in the Southern California mountains in the 1940s," Pedersen said. "I worked there every summer with my brothers until I graduated from Stanford (AB '65). When our major customer went out of business, though, our sawmill and lumber yard did, too." When NIH terminated the Varmus-Clinton program in early 2001, Pedersen said he "could see the handwriting on the wall" about support for his lab's human embryonic stem cell research.

As a result, Pedersen got back in touch with Sir Keith Peters, which led to him securing a chair as professor of regenerative medicine at Cambridge. In addition to obtaining his own lab's stem cell research funding from a variety of sources, his other major task was to organize the Cambridge stem cell center by winning Medical Research Council funding.

"When I arrived there in September 2001, I found myself in a supersaturated solution of talent and ideas," Pedersen said. "My arrival in Cambridge was the seed that nucleated the Cambridge Stem Cell Initiative. It started a centripetal process that gained coherence like a hurricane."

One key piece of advice he got was to lead from the rear, Pedersen said. "Sir Keith advised me that I should be the secretary of the initiative's management committee, not its chairman," he said. "The Cambridge Stem Cell Initiative is a case study in academic persuasion. By achieving consensus and a single voice, the initiative was able to secure university space and capital support so we could recruit other major players in the stem cell field, like Austin Smith and Fiona Watt, who in turn raised additional funding from the Wellcome Trust. This ultimately led to Cambridge's Stem Cell Institute (as it is now known) becoming the U.K. and European flagship for research in stem cells and regenerative medicine."

After Pedersen left for Cambridge, his name was often cited in the debate about restrictions on stem cell research. His departure was a concrete example of how federal restrictions thwarted research by discouraging and driving away some of the brightest stem cell scientists. The threat that California could lose other researchers was a driving force behind Proposition 71. Its passage established the California Institute for Regenerative Medicine, which provides funding for California researchers doing stem cell research and encourages top stem cell scientists to move to California rather than away from it. Many other states have since created similar efforts, though with substantially less funding for research.

Pederson said he is happy that CIRM funding has contributed to the "very good health" of California's stem cell research efforts.

While at Stanford, Pedersen will devote himself to a question that most people might think has already been answered. "We really don't know the capacity of human embryonic stem cells for normal tissue development," he said. The question is crucial for the future of stem cell therapy because researchers are counting on the ability of embryonic cells to grow into normal, mature tissues.

Pedersen points out that if you put a mouse embryonic stem cell into a blastocyst (the early, hollow-ball embryonic stage), it will contribute to all of the various tissues in a developing mouse, but human embryonic stem cells have never been assessed for this ability.

"Doing this experiment with human embryonic stem cells is daunting not only for ethical reasons, but also for technical reasons, because embryonic stem cells from mouse and human have very different properties," he said.

However, Pedersen and his colleagues have recently identified a novel type of stem cell from the "epiblast" layer of slightly later stage mouse embryos. These epiblast stem cells have properties extremely similar to those of human embryonic stem cells, and they allow the researchers to do experiments that more closely model the behavior of human embryonic stem cells. Pedersen said, "They can also lay the groundwork for any future studies that would test the developmental capacity of human stem cells more directly." If epiblast stem cells (and ultimately, human embryonic stem cells) can contribute to fully functional, mature tissues, this will have major implications for regenerative medicine and hoped-for stem cell therapies, he said.

"Our optimistic hypothesis is that the human embryonic type of stem cells can indeed do all the things we expect from normal development, just like classical mouse embryonic stem cells, but we just don't know that yet. I would like to find out if they can.

Christopher Vaughan is the communications officer at the Stanford Institute for Stem Cell Biology and Regenerative Medicine.