Geneticists insist that reproductive cloning does not work well for animals, and that clones are prone to illness and a short life span. The clones also don’t look like replicates of the parent. They are genetically identical, but environmental factors in the womb cause the clones to develop different features. For instance, a company in California recently cloned a calico cat that was born with a different calico pattern from its genetic “parent.” “So little Bobby’s clone won’t look like the original Bobby,” the pioneering molecular biologist Sydney Brenner told me. “Besides,” he said in his dry South African – British accent, “I can find much more pleasant ways of reproducing children that do not involve cloning.” Yet someone will one day most likely clone a human being, if no one has already. The scientists say that the technology is difficult, possibly impossible, though they used to say cloning a sheep would be impossible—and then came Dolly in 1997. “That will be a disaster,” says Melton, “first for the child, but also for science, if the child ends up getting sick and dying, or becomes an object of revulsion and ridicule.”
The controversy over embryonic stem cells being a force of good or evil is as old as fire. The Promethean myth is not just about a sympathetic god who gives mortals fire. A cautionary tale about the dangers of delving too much into the mysteries of the gods, it also underscores the dual nature of scientific discovery—that fire is a potent tool for improving life but can also be a force of destruction. Cro-Magnon scientists undoubtedly pointed to fire and realized the possibilities: Charbroiled mammoth steak! Torchlight to paint bison on cave walls! Cro-Magnon skeptics agreed that mammoth kabobs were better barbequed than raw, but what if the flames leapt up in a gust of wind and razed the village, burning people alive? For aeons, the profire and antifire forces have seesawed back and forth as the prevailing viewpoint when new technologies and discoveries appeared. Fire is still rightly feared in certain forms, and we have strict laws about arsonists and others who abuse it. Yet humans long ago decided the basics about what’s useful and dangerous about fire. We have imposed sensible regulations on its use, striking a balance that we can only hope will one day prevail for the work of Doug Melton and his fellow fire-bringers.
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Doug Melton grew up on the South Side of Chicago in a working-class home. 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 public high school. “I went to a rather difficult high school,” he says. “It was right after Martin Luther King had been killed. There was that period of race riots. It wasn’t exactly what I would call a college preparatory school. It was a huge school on the South Side of Chicago—I think there were nine hundred students in my class, bigger than some colleges.”
Leaving Chicago for the University of Illinois, Melton discovered the world of the mind as a biology major. “For the first time in my life, I felt myself part of an intellectual world,” he says, and he loved it. Melton excelled at Illinois and won a Marshall Scholarship to study at Cambridge University in England, where he earned a second undergraduate degree in history and philosophy of science at Trinity College. He stayed on at Cambridge to earn his Ph.D. in molecular biology, working at the famed Laboratory of Molecular Biology (LMB) and training under the legendary geneticist John Gurdon. Gurdon’s breakthroughs in the fifties and sixties were key to the experiments performed by Ian Wilmut, the former Gurdon student who went on to clone Dolly the sheep. In the early sixties, Gurdon showed that by inserting a mature, differentiated frog cell into a frog egg stripped of its nucleus you could create an embryo that would grow into a clone of the original frog. Melton was also mentored by Sydney Brenner, then the head of the LMB.
In 1980, Melton left England for Harvard. There he launched his research on developmental biology, working to catalogue growth-factor proteins called morphogens that control the development of organs, including the nervous system. In one experiment, one of Melton’s postdocs, Hemmati Brivanlou, an Iranian raised in France, knocked out the action of the growth factor activin just after a frog egg was fertilized. The result surprised Melton and Brivanlou by shutting down the usual formation of the embryo, causing it to stall out. On closer inspection, Brivanlou realized that the lack of activin had stopped the development of a mesoderm, the layer of tissue that forms in an embryo that eventually develops into muscle, bone, and connective tissue. More astonishing was that nearly all of the cells in the failed embryo had turned into brain cells, simply by shutting down this single protein.
“For some years I studied what happens right after fertilization,” says Melton; “that is important for telling cells what to become, the problem of developmental biology. 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.” That is, one end of the egg develops differently than the other end.
“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.”
Melton also made his name with Hal Weintraub of the Fred Hutchinson Cancer Center in Seattle as the first to report on antisense techniques. This process uses artificial nucleotides—bases that are created by scientists beyond nature’s A, C, T, and G—to shut down genes that cause disease by attaching synthetic “antisense” sequences to messenger RNA. These delivery vans of the cell can’t make their scheduled delivery to the ribosomes, which then don’t translate the melodious gene into the protein or reaction that causes the disease. During the late eighties and early nineties, the potential offered by antisense generated intense interest in biotech companies, and Melton cofounded Gilead, a biotech start-up launched to investigate whether compounds developed using antisense techniques would work as drugs. Unfortunately, antisense turned out to cause side effects—and Gilead went on to develop other drugs. “Antisense has never been used as a drug,” says Melton, “even though the idea’s an intriguing one.”
In 1991, Melton was happily working on basic developmental biology with his frogs when one November night Sam, then six months old, started vomiting. What at first looked like a virus grew worse. When Sam went limp, Melton and his wife, Gail, rushed their baby to the emergency room at Children’s Hospital in Boston. Sam was near death when doctors realized that he has diabetes, the youngest person ever diagnosed with diabetes at Children’s. Sam recovered, and his condition launched the Meltons on the regimen of keeping an infant diabetic alive—frequent blood tests, a closely monitored diet, and up to five shots of insulin a day.
“I was there when that happened,” said Melton’s former postdoc Hemmati Brivalou to author Stephen Hall in his book Merchants of Immortality, “and we went through a very scary period.” Melton stayed home from his lab for several weeks, until Sam was out of immediate danger. He then returned and gave an emotional talk to his team. He said that he would continue the lab’s work but would concentrate on finding a cure for his son and others like him. “Sam’s situation forced me to think more about how to apply biology; how to make a difference.” Melton invited venture capitalists and entrepreneurs to the lab and founded another company, Ontogeny, to work on molecular treatments for diabetes and other diseases. Ontogeny is now part of Curis. Melton also began to study how stem cells develop into healthy and unhealthy islet cells. Melton’s daughter was diagnosed later with having acquired diabetes when she was fourteen years old.
In 1999, a few months after James Thompson’s isolation of human stem cells, the issue of embryos and cloning broke into public consciousness as the Clinton administration and Congress grappled with how to handle the controversial new discoveries. Eager to help shape the debate, Melton and other leading embryologists went to