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John Gearhart’s lab is closed to outsiders.

Rather than happening there, an interview brokered by a university public affairs officer takes place in a windowless lecture room in the bowels of the Johns Hopkins University School of Medicine. Outside, seedy east Baltimore vibrates with the energy of a bright spring day. Gearhart appears and takes a seat under the fluorescent lights. Time is short, and no tape recorders, please.

With reddish blond hair and a direct gaze, Gearhart speaks with excitement about the vast medical potential of the research going on in his lab. He describes the early stages of human life and an elusive cell found only in embryos. But there’s much about this conversation that’s fleeting, incomplete and evasive. Suddenly his voice turns defiant and he’s scowling deeply. He relates how he and his family have received threats, how other scientists have criticized his failure to publish and his close ties with industry. And then he is gone, sprung by the clock-conscious PR man.

If awards were given for the most intriguing, controversial, underfunded and hush-hush of scientific pursuits, the search for the human embryonic stem (ES) cell would likely sweep the categories. It’s a hunt for the tabula rasa of human cells-a cell that has the potential to give rise to any of the myriad of cell types found in the body. If this mysterious creature could be captured and grown in the lab, it might change the face of medicine, promising, among other remarkable options, the ability to grow replacement human tissue at will. The ES cell could, scientists hope, be a factory-in-a-dish that turns out cardiac muscles to patch heart attack victims, neurons to mend paralysis or pancreatic cells to battle diabetes. “It’s a treasure house of opportunity for developing fundamental knowledge and medical applications,” says Michael McClure, chief of the National Institute of Child Health and Human Development’s Reproductive Sciences Branch in Bethesda, Md.

That all sounds so promising. Why, then, is John Gearhart besieged? The answer is that these cells are found only in embryos or very immature fetuses, and pro-life forces have targeted the researchers who are hunting for ES cells, hoping to stop their science cold. In addition, the federal government has barred federal dollars for human embryo research, pushing it out of the mainstream of developmental biology. To make matters worse, human ES cells could conceivably provide a vehicle for the genetic engineering of people, and the ethical dilemmas surrounding human cloning threaten to spill over onto this field. Deprived of the federal funds that power most basic biomedical research and surrounded by fierce controversy, the hunt for the ES cell is being undertaken only “by a few brave souls,” says Colin Stewart, a colleague of McClure’s at the National Institutes of Health (NIH).

Extensive reporting by TR suggests that in the United States, those brave souls are drawn from fewer than a half-dozen research groups. There are also a few others in the United Kingdom, Australia and Singapore. Even this intensive survey may have missed some researchers, since some probably prefer to do their work in silence. “We’re constantly wondering what our competitors are doing, and even who they are,” says Gearhart, director of research at the Johns Hopkins department of gynecology and obstetrics.

Taming the human ES cell wouldn’t just be a huge scientific coup-it would also be a potential gold mine for the biotech firm that took out an enforceable patent on the tabula rasa cell. But the same secrecy and controversy that dogs the researchers has also limited the open involvement of industry. Just one company is openly chasing the human ES cell-Geron of Menlo Park, Calif. This young Silicon Valley firm has aggressively signed collaborations with leading ES researchers, including Gearhart and Roger Pedersen, a reproductive biologist at the University of California, San Francisco (UCSF). A search of the U.S. patent filings also shows that a small startup in White Plains, N. Y., called Plurion, is building up intellectual property around the ES cell. But Plurion executive Mark Germain declines to comment further.

“It’s a taboo area,” says Doros Platika, CEO of the Cambridge, Mass.-based startup Ontogeny, a rising star in the developmental biology business. “Big pharmaceutical companies are afraid to touch it. And the field needs to sort itself out before we’d get into it.”

In spite of all these difficulties, there is a healthy scientific competition to catch the human ES cell-driven both by the desire for scientific glory and by the riches that might come with controlling the fabled stem cell itself. “It’s a race. I lose sleep,” Gearhart says. And despite many technical difficulties, several labs-including Gearhart’s-believe they may already have captured the ES cell and are working to characterize and control the cells, furiously filing patent applications as they go.

Furious scientific competition, threats of violence, huge medical potential, fear and secrecy. Welcome, behind closed doors, to the topsy-turvy world of the human embryonic stem cell.

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