Читать книгу Masterminds: Genius, DNA, and the Quest to Rewrite Life - David Duncan Ewing - Страница 11

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 Washington to testify in favor of moving ahead with stem cell research. In a pivotal Senate hearing held by the Labor Health and Human Services Subcommittee, chaired by Pennsylvania Republican Arlen Spector, he appeared on behalf of the Juvenile Diabetes Research Foundation. Speaking, he said, as a parent, Melton described the exhausting regimen of being the father of a seven-year-old diabetic. “I can’t recall a single night since Sam was diagnosed when we slept peacefully, free of the worry that the balance between his food, insulin and exercise was not good enough. I’m unwilling to accept the enormity of this medical and psychological burden and I am personally devoted to bringing it to an end for Sam and all type I diabetics.”

He told the senators that stem cells offered hope for Sam and others and described the promise for producing healthy islet cells that could be transplanted into a patient, or for producing bioengineered islet cells that would not be susceptible to an attack by a patient’s immune system. He talked about the ethical quandaries but said that he and the diabetes foundation “feel that appropriate safeguards can and should be established,” suggesting, as other proponents do, that stem cell research should be federally funded. Soon after, he joined a task force to help form the policies of the Clinton administration, which determined in 2000 that stem cells were not embryos under an act of Congress that forbids research on human embryos. The Clinton White House—and, presumably, a succeeding Gore White House—was poised to allow broad funding of embryonic stem cell research with safeguards when George W. Bush was elected. When the Bush administration at first failed to take any action on furthering stem cell research, Melton joined James Thompson and others in a lawsuit to force action, which was obviated when President Bush announced his stem cell policy in August 2001.

In 1990, the former president George H. W. Bush, the first Bush president, summed up the idea of scientific balance in a meeting of the National Academy of Sciences. “Science, like any field of endeavor, relies on freedom of inquiry; and one of the hallmarks of that freedom is objectivity.” Under his son, President George W. Bush, and the Republican-led Congress, the pendulum in the debate between objectivity and ideology has taken a different swing. In 2003, the House of Representatives passed a bill calling for a complete ban on all forms of human cloning. The bill lumped together embryonic cloning to create stem cells with reproductive cloning, which virtually everyone believes should be banned. Under the proposed legislation, Doug Melton and his colleagues would face up to ten years in prison and fines of at least $1 million for cloning embryonic stem cells. In the 2003–2004 Congress, the Senate’s version of the bill failed to muster enough votes to pass. Proponents of a full ban and criminalization have vowed to introduce the bills again in the current Congress, which includes added numbers of conservative Republicans who are likely to support this legislation.

In the United Nations (UN), the Legal Committee of the General Assembly in 2003 defeated by one vote a measure to recommend to the full assembly a ban on all cloning, deciding to reconsider the issue in two years. Had the ban initiative reached the floor of the full assembly, a United States – led coalition advocating the ban looked likely to win, as the Bush administration claimed to have the support of 100 of 191 members. Such a ban would be nonbinding, but should it pass, it would send a loud message. The UN briefly reconsidered the measure in 2004, spurred on by the Bush administration, but again decided to postpone a vote.

I ask Melton whether he ever thought he would be jumping into the middle of a politics maelstrom like this.

“No, I never really thought much about that. It’s related to the accident of my own family history.”

“What has the experience taught you?”

“I was so naïve about the political process,” he says, “about how important policy decisions are made. I found that shocking. So I started to speak out, particularly against bioethicists, who I think are self-appointed priests of certain political views, saying to them, ‘I don’t know why you think you have the right to say what is ethical and what isn’t, and that my own views should have as much validity as theirs.’ I find that when most people say ethics what they really mean is ‘moral,’” he adds, “and that it has to do with their religious beliefs. No one’s really trying to do unethical things.”

He is dismissive of most of the bioethicists appointed by Bush to the President’s Council of Bioethics, a committee that is supposed to base its decisions on scientific findings but has been criticized by Melton and others for undue partisanship. He finds the chairman of the council, the University of Chicago physician and bioethicist Leon Kass, to be “extremely political.” Kass is a strident opponent of many genetic therapies that might be used to enhance or alter humans. He opposes efforts to extend life span by using genetics, and although he supports some stem cell research for medical treatments, he opposes the destruction of embryos to secure stem cells.

I ask Melton what he thinks the role of government should be for something like stem cells.

“I think the government needs to create the conditions for what I would call an informed debate,” he says. “And it’s not easy for someone sitting in my position to say that without sounding arrogant, but the simple fact is that our Congress doesn’t often think about the things that they’re trying to legislate on. They don’t educate themselves on what is the basic biology. And I can give numerous examples. A wonderful question was asked to people who are writing legislation on AIDS, if they know the difference between a cell and a virus. Most didn’t.”