“Simple Approach” May Defuse Complicated Stem-Cell Controversy

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Class of ’85 | When the news broke last November that the University of Wisconsin research team led by pioneering developmental biologist James A. Thomson V’85 Gr’88 had successfully transformed ordinary human skin cells into undifferentiated stem cells, the reaction was instantaneous—and just a tad breathless. Some scientists predicted that the breakthrough would revolutionize medicine. (“This is the biological equivalent of the Wright Brothers’ first airplane,” enthused Dr. Robert Lanza C’78 M’83, chief scientific officer of Advanced Cell Technology.) Others speculated that Thomson’s discovery would defuse the ongoing controversy over using human embryos, thus giving molecular biologists a clear field on which to expand their cutting-edge research.

Within hours of its announcement, the successful development of the new stem-cell manufacturing technique produced a flurry of dramatic headlines at The New YorkTimes and CNN. Unfazed, however, Thomson remained characteristically low-key and understated about his lab team’s success at tricking skin cells into becoming undifferentiated cellular factories. (With further development, the technique may one day be used to create everything from new heart tissue to new kidneys.)

“I do think it’s a fairly important discovery, but you gotta wait a hundred years to see how important,” quipped the 49-year-old Thomson, whose findings were published in Science last fall (www.sciencemag.org/cgi/content/abstract/1151526).  “In this field, it usually takes a long time for things to sort themselves out.  If you remember, the Wright Brothers flew their first plane in 1903 . . . and by 1907 it still looked like [nothing more than] a curious plaything.”

The calmly methodical Thomson did his best to underplay the discovery of a new tool that promises to give developmental biologists access to a limitless supply of human stem cells—without requiring them to cannibalize discarded human embryos.

“We’ve made a pretty good start,” Thomson reflected during a recent interview with the Gazette, “but it’s also important to remember that we actually know very little about the processes of human cell differentiation. We’re only at the beginning, really, and it will be a long time before we see the impact of this kind of research on medical care.”

So how did Thomson’s Wisconsin lab team—which also included Penn’s Junying Yu Gr’02—go about the process of convincing skin cells to masquerade as pluripotent stem cells?  “Actually, the steps were surprisingly simple,” says Thomson. “As a matter of fact, they were so simple that many researchers, including myself, didn’t believe it could be done this way.

“What we did was to insert a series of [human chromosomal] proteins into the skin cells … which basically reversed the process of differentiation. In simple terms, you could say that we found a way to get the cells to go ‘backwards’ in their development, so that they reverted to the stem-cell potency they’d possessed before becoming skin cells.”

For Thomson, whose discovery was announced last November on the same day that a high-profile Japanese team made a similar breakthrough, the synthesizing strategy depended as much on common sense and a “willingness to explore simple solutions” as it did on high-tech molecular wizardry.

“I’m pretty good at growing things, which is why I like gardening in the backyard,” joked Thomson. “This is certainly a nice step, because it’s going to give us a powerful new tool to look at cell lines with—but it won’t change anything overnight, and we’re well aware of the fact that we don’t know much about the actual biochemistry involved.”

Thomson was a Phi Beta Kappa biophysics whiz at the University of Illinois, graduating in 1981. After earning his degree in veterinary medicine from Penn, he studied under renowned molecular biologist Davor Solter at the Wistar Institute. There he met wife Ruth Sullivan V’91 Gr’96—today a pathologist and cancer researcher at the University of Wisconsin—and also spent a lot of his spare time pursuing an avid interest in amateur aeronautics.

“I joined a hang-gliding club on campus,” he recalls, “and I also had a lot of fun doing things like throwing boomerangs around.”  (He continues to hang and glide today, he says, on those rare occasions when he can escape from his lab in Madison.)

The recent stem-cell discovery carries a delightful irony for Thomson, along with the promise of future medical breakthroughs. As one of the nation’s first researchers to isolate and harvest stem cells from human embryos [“James Thomson and the Holy Grail,” Jan|Feb 2002], he played a major role in triggering the turbulent ethical controversy over this form of research, starting back in the mid-1990s. But when the news of his startling find wound up on the front page last fall, the White House seemed to go out of its way to applaud him.

After describing President George W. Bush as “very pleased” by Thomson’s discovery, the White House press release noted that the president “believes medical problems can be solved without compromising either the high aims of science or the sanctity of human life.”

Thomson says he couldn’t agree more—but then points out that his team didn’t set out to transform skin cells into stem cells in order to neutralize the political and ethical issues over the technique.

“Actually, we were just looking for a quicker, better way to produce stem cells,” he says, “and we happened to come up with an approach that doesn’t require embryos. If this helps to solve the ethical issues involved, so much the better.”

—Tom Nugent

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