PHILOSOPHER-SCIENTIST: Harvard embryologist Doug Melton argues that efforts to outlaw embryonic stem cell research are rooted in archaic notions of what is natural. "You know, people once thought cutting into the body was a sin," he says. "Now it's normal. Society's increase in knowledge and practices and beliefs can have a serious effect on what's natural."
Sitting in Doug Melton's Harvard University office on a spring day, I look at the faces of his children in photographs on the desk. Sam is 14 years old now, with short hair and a slightly awkward smile; Emma has long, dark hair and serious eyes. 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. Her father says, "I just hope she gets the chance." 
Inside Sam and Emma is an immune system that has destroyed cells called islets that are responsible for producing insulin in the pancreas. Insulin is an enzyme that helps transport sugars from the blood into cells for use as fuel. Without it, sugars gum up in the blood vessels as sugar does in a gas tank, causing an untreated diabetic to go into shock and die. Most diabetics today are saved by frequent shots of synthetic insulin, but the balance between blood sugar and injected insulin is a crude calculation. Diabetics receive either too much or too little insulin each day, which causes damage to organs and muscles. For Melton's children, this imbalance is most likely an early death sentence, unless, of course, their father can discover a stem cell fix for pancreatic cells in diabetics that are inexplicably attacked by the body's immune system.
Melton's Prometheus-like resolve to give the embryological equivalent of fire to his children is evident from the floor plan of his office. Unlike the offices of most senior science professors here and at other elite institutions, which can resemble those of the world headquarters of a corporation, Melton's digs are nondescript. As I sit with him at a small table near his desk, it's clear where he would rather be—in his adjacent personal lab, also unusual for a superstar scientist. "I don't want to waste any time," he says.
Melton's determination and humble earnestness are immediately clear. With undergraduate degrees in both biology and philosophy and a Ph.D. in molecular biology, he seems to love nothing more than a passionate, long-winded argument.
But his arguments can be surprising. For instance, he wonders—just an intellectual puzzle, he assures me, that he would never want to do—What would happen if scientists injected human stem cells into a monkey embryo? What would grow? A human heart, a human brain, a toe? "That," he says, "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 suggest that an experiment like that might seem bizarre to many people. He agrees but argues that it will seem 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. He is intrigued by what is seen as normal or abnormal. Like many scientists, he likes to live in a space at the edge of what is possible.
Doug Melton grew up on the South Side of Chicago. His father managed a grocery store, and his mother was a court reporter. He says he spent most of his time playing tennis and basketball and trying to avoid the violence and tensions in his racially charged high school. "I went to a rather difficult high school," he says. "It was right after Martin Luther King had been killed.
At the University of Illinois, Melton discovered biology. "For the first time in my life, I felt myself part of an intellectual world," he says. He excelled and won a Marshall Scholarship to study at the University of Cambridge in England, where he earned his second undergraduate degree in history and philosophy of science at Trinity College. He stayed on to earn his Ph.D. in molecular biology at Cambridge, training under the legendary geneticist John Gurdon, whose breakthroughs in the 1950s and 1960s were key to the experiments performed by Ian Wilmut, a Gurdon student who cloned Dolly the sheep in 1997.
LONELY QUEST: Other leading scientists leave the details of basic research to graduate students or postdocs, but Melton spends as much time as possible working at a private lab bench adjacent to his office. He prefers to do his lab research alone because he does not want any distractions. Melton's ultimate goal is to discover how embryonic stem cells grow into special cells called islets in the pancreas. Islets produce insulin in a healthy person but shut down and stop functioning in someone who has diabetes.
After Cambridge, Melton went to Harvard, where he threw himself into developmental biology, working to catalog growth-factor proteins called morphogens that control the development of organs. In one experiment, one of Melton's postdocs, Ali Hemmati-Brivanlou, knocked out the growth factor activin just after a frog e gg was fertilized. The result was surprising: The embryo failed. On closer inspection, Hemmati-Brivanlou realized that the lack of activin had stopped the development of the mesoderm, a layer of tissue in an embryo that eventually develops into muscle, bone, and connective tissue. Nearly all the cells in the stalled embryo had turned into brain cells, simply because a single protein had been stopped. 
"For some years I studied what happens right after fertilization that is important for telling cells what to become," says Melton. "And among the areas we worked in were studies on a process called localized messenger RNA. So if you think about the egg as sort of a uniform ball, you put a messenger RNA on one end of the egg, and when you cut up the ball, then only the cells at that end get that information. It's a way of making one end of the egg different from the other.
"Through studies like that, we've been able to show how the main so-called germ layers for the embryo are formed—ectoderm, mesoderm, and endoderm. And many people found interesting the hypothesis we put forth, which now seems to have even more experimental support: that the nervous system forms by a kind of default mechanism. It's the easiest thing for the embryo to form. That was sort of surprising, because neurobiologists wanted to believe that neurons were the highest, most complicated types of cells."
One night in 1991, Melton's 6-month-old son, Sam, started vomiting. What seemed like a virus grew worse. When Sam went limp, Melton and his wife, Gail, rushed the baby to the emergency room at Children's Hospital in Boston. Sam nearly died before doctors finally realized he had diabetes, the youngest person ever diagnosed with the disease at Children's Hospital. Sam recovered, but his illness launched the Meltons into an overwhelming regimen of keeping an infant diabetic alive—blood tests every few hours, a closely controlled diet, up to five shots of insulin a day.
"I was there when that happened," said Melton's former postdoc Hemmati-Brivanlou to the author Stephen S. Hall in his book Merchants of Immortality, "and we went through a very scary period." Melton stayed home from his lab for weeks, until Sam seemed out of immediate danger. Then he returned and gave an emotional talk to his team. He said that he would continue the work in the lab but would concentrate on finding a cure for his son and others like him. Melton began to study how stem cells turn into either healthy or unhealthy islet cells. Later Melton's daughter was diagnosed with diabetes when she was 14.
DOUG MELTON
BORN
September 26, 1953 MOTHER
Betty Melton, court reporter FATHER
A. Melton, grocery store manager PH.D. THESIS
Gene injections into amphibian oocytes
