Stem-Cell Research: The Quest Resumes

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Even during the dark days of the Bush Administration's stem-cell restrictions, Melton helped keep the field going, culturing cells and getting them into labs.

Gregory Heisler for TIME

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The decision sent some leading scientists abroad, to Britain, Singapore and China, where the governments were more receptive to their work. Others who stayed behind but lacked private funding shifted their attention from embryos to the less versatile adult stem cells. Federally backed scientists, like Melton, who continued embryonic work were forced to adopt a byzantine system of labeling and cataloging their cell cultures and equipment so that government money was not used to grow forbidden cells — and government microscopes were not even used to look at them.

Those days may soon be over. Barack Obama campaigned on a promise to lift the research ban and support "responsible oversight" of the stem-cell field. For scientists, that means "we can stop the silliness," says Melton.

As welcome as that change will be, it may be less urgent now — owing primarily to the work of scientists like Melton. While embryonic stem cells remain the gold standard for any treatments that find their way into the clinic, newer techniques using the next-generation stem cells may soon surpass the older ones.

The Fighter
In looks and demeanor, Melton is the quintessential professor, soft-spoken and thoughtful, someone who appears more mentor than maverick. Born and raised on the South Side of Chicago, he developed an early fascination with animal development; that curiosity led to a bachelor's degree in biology at the University of Illinois in 1975, then a second undergraduate degree, in the history and philosophy of science, at Cambridge University on a Marshall Scholarship. Melton remained there for his Ph.D. work, studying under Sir John Gurdon — the first to clone a frog. At Harvard, Melton teaches a frequently oversubscribed undergraduate course on science and ethics, in which he uses his keen sense of logic to provoke. When the class discussed the morality of embryonic-stem-cell research, Melton invited Richard Doerflinger of the U.S. Conference of Catholic Bishops to present arguments against the field. Melton asked Doerflinger if he considered a day-old embryo and a 6-year-old to be moral equivalents; when Doerflinger responded yes, Melton countered by asking why society accepts the freezing of embryos but not the freezing of 6-year-olds.

Clearly, Melton does not shrink from a fight. As Washington's squeeze on stem-cell research tightened in the early part of this decade, he decided to take action, providing life support for what remained of the U.S. stem-cell community. Not convinced that an entire field could make much progress relying on a few dozen cell lines of questionable quality, in 2004 he used funds HSCI receives from the Juvenile Diabetes Research Foundation and the Howard Hughes Medical Institute, as well as from Harvard alumni, and developed a more streamlined method for generating stem-cell lines from embryos. He created more than 70 new ones and has since distributed 3,000 copies to scientists around the country for free.

"Doug drew a line in the sand," says Alan Trounson, president of the California Institute of Regenerative Medicine, the organization charged with dispensing state money for embryonic-stem-cell research. "He turned the tables on an Administration that was incredibly negative toward stem cells and showed [it] we are not going to tolerate being put out of this field by ideological views that we don't think are correct." Melton's motivation was, again, both professional and intensely personal. Two months after Bush announced his ban, Melton's daughter Emma, then 14, also received a diagnosis of Type 1 diabetes.

In part owing to the restrictive U.S. policy, the momentum in stem-cell research seemed to shift overseas. In 2004, South Korean researcher Hwang Woo Suk announced that he had generated the first human embryonic stem cells from healthy people — and in the following year, from afflicted patients themselves — using an abbreviated cloning method. The latter feat would mean that cardiac patients could essentially donate themselves a healthy new heart without fear of rejection.

The news was huge — but it was also a lie. In 2006, Hwang admitted he had falsified his results. (Melton's colleague at HSCI, Kevin Eggan, finally created embryonic stem cells from patients in 2008.) Although Hwang became a pariah, he had the right idea. Melton and others had been trying to do just what the Korean scientist claimed to have done — grow a new population of a patient's own cells. The key to the process is a supply of fresh, good-quality human eggs, which incubate skin cells taken from a patient. Building up such a stockpile, however, proved practically impossible. The egg-extraction process is invasive and carries certain risks; after the state of Massachusetts prevented donors from being compensated for their eggs, out of fear the women would feel coerced, HSCI ended up with only one volunteer out of more than two years of recruiting.

Melton faced mounting political pressure too. In 2004, voters in California approved a measure providing $3 billion in state funding to embryonic-stem-cell research. That threatened to draw scientists in the stem-cell community west, and Melton took pains to foster a "band of brothers" mentality. "I tried to create a cocoon here," he says, "and tell people that your job is to focus on the science. Don't worry what the politicians say." By then, Melton's team was one of only a handful in the country working on embryonic stem cells and was making headway in teasing apart the myriad critical steps needed to guide these impressionable cells into becoming insulin-generating cells. Both as a scientist and as a father, Melton remained convinced that the federal restrictions simply could not survive. He continued to insist that "the science is so significant that it will change the policy."

And then, astonishingly, it did. In June 2006 a modest researcher from Japan made a startling announcement at the International Society for Stem Cell Research conference in Toronto. Shinya Yamanaka quietly described a study in which he took skin cells from a mouse and stirred them in with varying genetic cocktails made from a recipe list of 30 genes known to be important in development. When he hit on the right four genes and inserted them into the cells aboard retroviruses, he wiped the cells clean, reprogramming them and returning them to an embryo-like state without ever creating the embryo. Four genes, he told his audience, was all it took to undo a lifetime's worth of delicate genetic tapestry. No need for eggs, no need for embryos. Could it be that easy? Were the debate and controversy over embryonic stem cells now rendered moot? "It was unquestionably unexpected," says Melton of the breakthrough.

Read a TIME cover story on Stem Cells.

See the Year in Health, from A to Z.