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Sitting in Melton’s office on a cool, bright spring day in Cambridge, I look at the faces of his children in photographs on his desk. Sam is lanky with short hair and a slightly awkward smile; Emma has long, dark hair and serious eyes. Now a college freshman, Emma once wrote in an essay that she wants to become an embryologist like her father. “I am also interested in becoming a member of Congress and petitioning for a cure that way,” she wrote. “I just hope she gets the chance,” says Melton. “In this, I am no different than any parent.”

Inside Sam and Emma and 1 million other in-sulin-dependent diabetics in the United States, the body’s immune system inexplicably attacks islet cells as it would a foreign invader such as a virus, an autoimmune response that destroys these cells’ ability to produce insulin. Insulin is an enzyme that helps transport sugars from the blood into cells for use as fuel. Without it, the sugars gum up in the blood vessels as sugar does in a gas tank, causing a patient with full-blown, in-sulin-dependent diabetes to go into shock and die. Most diabetics today are saved by frequent shots of synthetic insulin, though the balance between blood sugar and injected insulin is often a crude calculation. Almost all diabetics receive either too much or too little insulin at various times, a situation that can cause gradual damage to organs and muscles over the years. For Melton’s children, this imbalance may be an early death sentence, unless researchers can find a treatment or a cure for the islet dilemma. One of the most promising is for their father or another stem cell researcher to discover a stem-cell fix for pancreatic cells.

Melton’s resolve to give the embryological equivalent of fire to his children is evident from the floor plan of his office at Harvard. Unlike most senior science professors here and at other elite institutions, where offices of big shots often resemble the world headquarters of a company, or a nation, with staff, awards, and reprints of papers everywhere, Melton’s nondescript office is connected to a personal lab that is separate from his team’s main labs down the hall. His office has some of the expected awards and reprints, too, but as I sit with him at a small table near his desk, it’s clear where he would rather be. “I don’t want to waste any time,” he says, popping up to show me the small work station where he tries to tease out the mechanisms of how a stem cell makes the transformation into a pancreas.

Melton may be soft-spoken, but he has become a firebrand for his children, and for his science, openly defying the Olympians in Washington who oppose his research. Several times he has traveled to Washington to give testimony to Congress, especially after President Bush announced in August 2001 that federal funds for stem cell research would be restricted to sixty-four frozen embryonic stem cell lines already culled from existing embryos. These “lines” are special groupings of stem cells coaxed to replicate to produce more stem cells, and not to develop into other cells. These lines are critical for research, though acquiring them is controversial because the only source at the moment is to snatch them out of embryos grown in petri dishes, a process that causes the embryos to be destroyed. To some people, this is murder. To others, the embryos are simply a grouping of cells that are incapable of becoming human beings unless they are in a womb. As Melton and other scientists point out, thousands of embryos are discarded every year during in vitro fertilization procedures, though under the Bush rules, scientists using federal funds are banned from using them.

The president banned the development of further lines with federal funds, although the restriction does not affect private or statesponsored funding. Bush’s position sounded like a compromise, but it quickly became evident that the sixty-four lines did not really exist. The actual number of cell lines widely available to researchers has turned out to be far fewer, a stem gap that is hampering research paid for with U.S. money—the lion’s share of all funding for scientific research. Some of the approved lines are either in the hands of private entities, or have been tainted by mouse cells that make them unusable for human research. “There was this idea now that there are these sixty or seventy cell lines which the administration claims exist,” says Melton. “I think the number is closer to five to ten.”

Soon after President Bush announced his policy, Melton and others launched various crusades to get around the restrictions. At Harvard, Melton worked to assemble funding from the privately endowed Howard Hughes Medical Institutes, where he is a chief investigator, the Juvenile Diabetes Research Foundation, and other nonfederal sources. In March 2004 Melton announced that he had developed seventeen new embryonic stem cell lines, available to any researcher who has access to nonfederal funds. He also is director of Harvard’s new stem cell institute, which has raised $100 million for stem cell research from private donors. In California, scientists, universities, and their political supporters sidestepped the Bush rules in November 2004 when voters passed a state referendum approving $3 billion in bonds to fund stem cell research at the state level—including research using embryonic stem cells. This referendum will fund stem cell research in California at $300 million a year for ten years.

Across the sea, the British Parliament has passed regulations allowing government-funded embryonic stem-cell research, with safeguards, which went into effect in 2003. Singapore, China, South Korea, and other nations are also vigorously moving ahead with stem cell research.

Researchers are a long way from using stem cells to cure Sam and Emma, or anyone else. Stem cells may never work as treatments for many diseases, though at the very least, says Melton, they will help scientists understand the basics of how organisms develop and why mistakes occur that cause people to suffer. Yet researchers hope that someday these microscopic blobs might be tweaked to grow into healthy aortas to replace cells damaged by heart disease, or into a pristine spinal cord for someone like the late actor Christopher Reeves, who was paralyzed when his backbone was shattered in a horseback-riding accident. Nancy Reagan has also talked about her hope that stem cells can regenerate cells in the brain damaged by Alzheimer’s disease, which killed her husband, the former president Ronald Reagan.

Researchers also experiment with adult stem cells, created in each of us throughout life by specific organs such as the skin, which uses these stem cells when they grow into specialized replacement cells. However, not all organs and bodily systems have adult stem cells, and even when they do, these cells are not always as useful in repairing and regenerating as embryonic stem cells that have the potential to differentiate into anything. In the summer of 2004, Melton announced the results of an experiment that indicates there are no adult stem cells to regrow islets in those who suffer from type I diabetes.

Before his children grew ill, Doug Melton was an ambitious young researcher conducting leading-edge research in developmental biology using frogs, though he was perfectly content with a high-profile position in academia, writing exceptional scientific papers and getting kudos from his peers. His forays into politics and the media began only after he discovered Sam and Emma had diabetes, when Melton made the switch into pancreatic stem cell research. “I’m an activist now, I guess,” he says, smiling shyly. Most of his testimony and appearances are on behalf of the Juvenile Diabetes Research Foundation, which also has helped to fund his new stem cell lines.

Melton has a calm, private energy compared to other more fiery egos who appear on these pages. He has an earnestness about his work, a sense of humility that is not feigned, and less of a restlessness and a need to accomplish fantastic feats for all to see. He is not trying to rankle people with grandstanding ideas or using science as a vehicle to fame and glory. With undergraduate degrees in both philosophy and biology, and a Ph.D. in molecular biology, Melton loves nothing more than a vigorous intellectual argument. This is how he likes to present his ideas, with a passionate, long-winded, fascinating discourse.

Later, Melton will surprise me by presenting in the form of intellectual “puzzles” ideas that most of us would consider out there, such as, What might happen if scientists inject human stem cells into a monkey embryo? What would grow? A human heart, brain, or toe? “Now, this won’t happen in the next few years,” he says, “or even in the next few decades. But that, to me, is a kind of new biology that I find a million times more interesting than these specious arguments over whether life begins at fertilization.”

I mention to him that these experiments might seem bizarre to many people, and he agrees, though he argues that they will become normal one day. “There was a time when surgery was abnormal,” he says, when it was considered a violation of the body as the sacred vessel of the soul. “I’m intrigued by this issue of what is normal and abnormal,” he tells me, indicating that his ideas of normal may be different from most people’s—and that, as many scientists do, he gets juiced up by imagining scenarios just beyond what is now possible. This is a crucial characteristic of scientists, that they need to live in a space at the leading edge of what is possible, operating within the outer boundaries of acceptable ethical norms, but also pushing these norms into potentially new territory. This is what Melton is talking about with his puzzles.

Hopefully, Melton’s work and ideas will not result in his being chained to a mountain with a daily assault on a vital organ by a giant predator bird. Indeed, his comments about human brains in monkeys were posed as Socratic suppositions about what is normal, and what is not. Yet I also think that given the chance, and if ethically it was allowed, he’d perform the experiment—out of curiosity, to save his kids, and perhaps, to usher us into a new age of fire.

Masterminds: Genius, DNA, and the Quest to Rewrite Life

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