Stem Winder

Before James Thomson came along, embryonic stem cells were a researcher's dream. Now they're a political hot potato

By Frederic Golden

(TIME) -- When James Thomson, the once obscure University of Wisconsin scientist whose pioneering research triggered the great debate over embryonic stem cells, learned last week that President Bush was about to make his big decision on them, he coolly decided to do what he had planned to do all along. On the morning after listening to the President's speech at a neighbor's house ("I don't have television," he says. "I just watch DVDs on my computer"), he blithely went off hang-gliding in the hills near Madison. Good thing. As the lab Merlin who was first to create the magical cells in a Petri dish, Thomson knew his telephone would be jangling after the President's pronouncement. "I thought it better to clear my head before facing the media storm," he says, leaving calls unanswered.

Though somewhat disappointed with the restriction on creating new cell lines — he's cultivating five right now — he's generally pleased with the Bush decision. "The field will now go forward. It won't be limited to just a few labs, even if there are only a few dozen cell lines," he says. "That's the most important thing." Such altruistic concern for the progress of his chosen science is characteristic of the man. Even before he was caught in the limelight, he went about his experiments so conscientiously that they set the ethical standard by which all research in the field is measured.

In November 1998, when he was just nudging 40, he not only succeeded in culling stem cells from "surplus" embryos created at fertility clinics but also kept them alive and reproducing indefinitely. In effect, he stopped their biological clocks by preventing the cells from morphing into different tissues, as they would in undisturbed embryos. In the jargon of cell research, they were immortal. Only a few days later, fellow stem-cell researcher John Gearhart of Johns Hopkins University published word that he had success in cultivating a line of stem cells from the germ cells of aborted fetuses — though he graciously conceded that Thomson was ahead in the overall race.

These were astonishing achievements. For the first time, scientists had access to a cornucopia of undifferentiated cells that can grow into any one of the 200 or so cell types that make up a human being. That opened the door to remarkable possibilities, including replacement cells for malfunctioning pancreases, injured spinal cords and plaque-clogged brains. It also brought stern warnings. Though the sacrificed embryos were no more than hollow, pinhead-size clusters of a few dozen cells, destroying them for whatever purpose represented, in the mind of many anti-abortion conservatives, an assault on a human life.

Thomson, a tall and rumpled Ichabod Crane, is ill cast as a lightning rod. A developmental biologist at the University of Wisconsin's primatology center, he traces his passion for science to an inspirational rocket-scientist uncle. Imagine, the uncle once told him about his work for NASA, "they pay me to do this."

But it was biology that beckoned the gifted Oak Park, Illinois, teenager. Encouraged by Fred Meins, one of his professors at the University of Illinois, to try his hand at lab work, Thomson became intrigued by the mysteries of early development — the burst of biological activity when the fertilized egg implants itself in the womb, then starts dividing and forming the specialized cells that turn miraculously into various tissues in the body. Most researchers studying these events used mice, but Thomson, after earning a Ph.D. in molecular biology at the University of Pennsylvania, as well as a veterinary-medicine degree, turned to more humanlike rhesus monkeys. Even so, it took him nearly four years to isolate and cultivate their stem cells.

By 1995 Thomson was ready to try human cells, but first he asked himself searching questions that endocrinologist James Prihoda, his college roommate, sees as a sign of his deep "respect for life and strong feeling that there is a purpose to it." Is this research ethical? Is it moral? Thomson, a nonpracticing Congregationalist who is married to a fellow scientist and is the father of two young children, wasn't sure. He read every study he could get his hands on and consulted, among others, University of Wisconsin bioethicists R. Alta Charo and Norman Fost. Since the embryos he planned to use were doomed anyway — one of the arguments cited by Bush — he decided he was justified by the good that might come of the research. "I could not see that throwing them out was better," he says.

By contrast, two other groups chose a more provocative path. In early July, the Jones Institute for Reproductive Medicine in Norfolk, Virginia, made headlines by announcing that it had created embryos (from donated sperm and eggs) expressly to extract their stem cells. A few days later, a Massachusetts biotech firm, Advanced Cell Technology, disclosed that it was trying to create embryos using human-cloning techniques. The back-to-back developments surprised opponents and supporters alike, and brought new calls for a ban on all embryonic stem-cell research.

With no fanfare, Thomson set himself up in an off-campus lab under a nonprofit arrangement with the University of Wisconsin's alumni association. That way he freed himself from existing federal restrictions — and avoided jeopardizing the university's government-funded research. Geron Corp., the Menlo Park, California, biotech firm that was financing Gearhart's efforts, partly bankrolled Thomson's work in exchange for commercial rights. (Thomson, however, was free to distribute his stem cells to fellow academics.) Because he could afford only one part-time assistant, he ended up doing much of the work himself, getting up at 5 a.m. and trudging off to the lab, rain or shine, to tend his precious cells. "You have to watch them every day or they differentiate" — that is, start turning into specialized tissue. After six months of watching them divide and multiply without undergoing any change, he was sure he had mastered the art of growing his life-giving seeds and set about writing the scientific paper in Science that alerted the world to his coup.

Since then, Thomson, an intensely private person, has been lofted out of obscurity. He received a red-carpet invitation to the Wisconsin state capital from then Governor Tommy Thompson, now Bush's Secretary of Health and Human Services. He is still consulted by Thompson's office on stem-cell issues but wasn't contacted directly by the White House for last week's decision. (Ironically, Thomson is the lead plaintiff in a case titled Thomson v. Thompson, seeking to force NIH to underwrite stem-cell research.)

Last year Thomson testified before the U.S. Senate on the value of stem-cell research. ("Scared me to death," he says.) So far, he has sold embryonic stem cells (at $5,000 for two vials) to some 30 research groups. Though he believes stem cells may someday be used to replace the faulty cells at the root of diseases like Parkinson's, he sees a more fundamental and perhaps more important role for them: explaining why some cells grow up healthy while others get sick and die. "We are simply ignorant about very early development," he says.

What's next for Thomson? Apart from possibly applying for that federal cash the President has promised, it's "to get back to work" and, he adds wistfully, "to obscurity." No chance of that.

— With reporting by Dick Thompson/Washington