Czytaj książkę: «Masterminds: Genius, DNA, and the Quest to Rewrite Life»

1 PROMETHEUS Douglas Melton

There’s a natural fear of the unknown. On the

other hand, I think it’s uninteresting to live in

a society where one is so afraid of the unknown

that you won’t try new things.

—Douglas Melton

Harvard embryologist

Why did Prometheus do it? Myths about this god who gave fire to mortals against the express wishes of Zeus never explain his motive. But I’m going to make a guess. He had mortal children who were cold and tired of eating berries and gnawing on raw meat. And father Prometheus, who sat around Olympus with other gods warming his hands with glowing embers on cold nights, felt guilty. And that’s how we got fire.

Prometheus paid dearly. Zeus punished him for breaking a command to keep fire in Olympus by chaining him to a rocky crag, where his liver was eaten every morning by an eagle, only to grow back by the next morning, so the screeching bird could tear it out again.

The Harvard embryologist Doug Melton, fifty-one years old, makes no secret of his motive for pushing hard to develop a modern-day equivalent of fire—embryonic stem cells. These are special cells produced in the first days after an egg is fertilized that will develop into a heart, brain, skeleton, or any other part of the body of an organism. Melton wants to use stem cells to save his own children, fourteen-year-old Sam and eighteen-year-old Emma. They suffer from type I diabetes, which he hopes can be treated by understanding how stem cells grow into special cells called islets in the pancreas that normally produce insulin in a healthy person but shut down and stop functioning in a diabetic.

By extension, the cherub-faced Melton, with floppy, short, graying hair and round-rimmed glasses, hopes to save us all if he is successful in learning from stem cells how to cure his children, to spare them the organ failure, blindness, heart disease that eventually afflict many diabetics. If stem cells work as treatments, his work could be used to heal other illnesses, a list of maladies that afflict hundreds of millions of people around the world. That is, if Melton is allowed to continue his work by certain lawmakers in Washington, D.C., who today collectively play the role of Zeus.

1

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.

2

A researcher in obstetrics and gynecology at the National University of Singapore, Ariff Bongso, first grew human stem cells in 1994. In 1998, the University of Wisconsin’s James Thompson isolated human stem cells for the first time. Yet scientists have known about stem cells in mice since the seventies. The original discovery in mice occurred when researchers were studying certain cancer cells, which they now know have many of the properties of a mouse’s embryonic stem cell that can grow into different types of cells. Melton says this promising line of research stopped, however, in the early eighties before a connection was made between what was going on in mice and humans.

“The field didn’t move forward at the time because of an historical accident,” he says, which was the discovery of recombinant DNA technology. This became all the rage and sidelined other research as scientists sought to learn about cell differentiation not through working with stem cells, but by recombining genes from different species, and also by removing, or “knocking out” genes in mice to see what impact all of this would have on a cell or organism. “It’s only now that people are going back to mouse [embryonic stem] ES cells, let alone human ES cells. And while they’re extremely useful for studying gene function in an animal, they also have their own inherent interest. Could you make body parts, tissues, ex vivo? That’s the field I’m very excited about, but we’re way behind.”

Since Bongso’s discovery in 1994, stem cells have ignited two firestorms. One is a creative fire, a breathtaking moment for Melton and other scientists, for whom a new world has been opened up for exploration that they believe will save countless Sams and Emmas. The other is political and ethical, the scorching debate that pits scientific optimists against skeptics who believe that this fledgling science may open up a Pandora’s box that could have unforeseen and catastrophic consequences.

For those who believe that life begins at conception, an experiment using embryonic stem cells is indeed a homicide. “We should not intentionally create life in order to destroy it, even for good purposes of scientific research,” says William Hurlbut, a Stanford physician and conservative bioethicist who was appointed by George W. Bush to sit on the President’s Bioethics Commission. He is not opposed to doing stem cell research, he says, just to acquiring the stem cells by destroying an embryo. “If we say that a human life in process should have a certain inviolable moral status,” he says, “then we protect ourselves against the dangers of both crossing a fundamental moral boundary and what other people call the slippery slope.” Hurlbut is closely connected to Catholic leaders and opposes abortion but says his convictions about the status of an embryo are based less on his religious convictions than on a fundamental belief that a line needs to be drawn to protect what it means to be a human.

Opposition does not arise from just the right-to-life camp. There are liberal secularists, too, who bring up Brave New World scenarios of baby farms where clones of you or me would be grown exclusively to provide spare parts—and farmed like a turnip or a chicken is now. Another fear is that stem cells will lead to designer babies engineered by using stem cells not merely to replace damaged cells in Melton’s children, but to add new cells designed to be supermemory cells, or super-muscle cells. The technoskeptic Bill McKibben frets that biotech companies and commercial interests are poised to patent stem cell discoveries, which may lead to biotech barons’ pushing stem cells and other bioenhancements on the public out of greed. “And they’ll be hard to police,” writes McKibben in his 2003 book Enough, “not only because they’ll contribute to political campaigns, but also because their work, day in and day out, won’t be dramatic enough to attract notice.” Many others who are not religious zealots or anticorporate warriors feel uneasy about the notion of creating a human embryo solely with the intention of harvesting its cells to benefit a full-grown human, though this unease may dissipate if cures are discovered.

A greater source of discomfort surrounds the use of cloning to create embryonic stem cells. Scientists believe that stem cells made from cloned DNA will work best to reconstruct spinal cords and liver cells in a specific person because the cloned cells are an identical genetic match and won’t be rejected by the body’s immune system. Rejection is currently a major drawback in transplanting hearts, kidneys, and other organs. Cloning also allows researchers to study how diseased cells develop in specific patients. To clone stem cells from, say, Sam Melton, a researcher would take Sam’s own DNA and implant it into a denucleated egg, which would hopefully grow into an embryo that contains Sam-specific stem cells capable of developing into pancreatic cells. These stem cells would be harvested and the embryo destroyed, although the embryo up until then could be placed inside a womb and theoretically taken to term, creating a full-scale clone of Sam.

Melton and other stem cell scientists insist that they have no intention of creating cloned human beings. But mistrust and fear of scientists and their motives lingers in a society that wants treatments and gizmos from science but fears its potential dangers and excesses. “I’ve had to face up to the fact that most of our society thinks of scientists as people who are likely to do something bad,” sighs Melton. “Either bad to make money for themselves, or to cause trouble in the Frankensteinian sense. And the fact is, scientists that I know are trying to do good for people.”

Rogue scientists and quacks have fed into the fear. In early 2003, a company called Clonaid claimed to have created a cloned human on behalf of a New Age sect called the Raelians, founded by a former race car journalist named Claude Vorilhon, a.k.a. Rael, who says that humans were cloned and brought to Earth long ago by aliens. When the baby failed to show up, and Clonaid refused to allow independent verification, their announcement was declared a hoax. More legitimate is the Italian embryologist Severino Antinori, who has claimed to be working to create a human clone in an undisclosed location. In February 2004, the cloning issue heated up when a South Korean research team led by Hwang Woo Suk of Seoul National University cloned thirty embryos of about one hundred cells each—by far the largest number grown to date. They then successfully extracted embryonic stem cells from one of the embryos. Stem cell advocates were ecstatic, while their critics pointed out that the Koreans could have planted their cloned embryos into a womb and attempted to grow a Xeroxed person. Also in 2004, the British government for the first time issued a permit under the Human Fertilization Authority for a team of scientists at the Center for Life in Newcastle to clone embryos to create stem cells.

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.

3

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.”

4

In Melton’s office he shows me his personal bench, telling me it’s a little unusual for a principal investigator in a large lab to do basic experiments. Typically, these are done by graduate students and post-doctoral students. He also points out that he intentionally has no windows here to prevent distractions. He tells me that the lab is using frogs, chickens, and zebrafish, but primarily mice for their experiments. The lab has tracked the phases of development of a pancreas from embryonic stem cells that form the endoderm and then go through a complicated series of steps involving the activation of genes and proteins that cause different organs to develop according to a programmed schedule in their DNA. Melton says that researchers have learned a great deal but still don’t know all of the genes and steps needed to drive stem cells from their undifferentiated state to fully formed islet cells.

“What are you actually doing in your lab?” I ask.

“In here now, mostly what we’re doing is trying to turn embryonic stem cells into pancreatic beta [islet] cells that make insulin,” he says. “And so we do that with two approaches: one is to take the human ES cells and just try to make them do that, and the other is to study how mice and chickens and frogs normally make a beta cell, and then use that to inform our thinking about humans.”

“So you actually have some stem cells right here in this lab?”

“They’re in the incubator down the hall.”

“And you’re using private money?”

“It’s a mix. I’ve had Howard Hughes money but more than half my lab’s funding comes from the federal government. But we’re not allowed to use the federal funds on these human ES cells.”

I ask him why he thinks people fear this sort of research.

“I think that’s a deeply interesting subject. What is the source of that fear and maybe to take a digression on it, I would tell you that my own view is that there is an innate fear to crossing boundaries; people feel secure with boundaries. Why have ideas of chimeras fascinated man for millennia? Minotaurs and mermaids? Why is that so intriguing? If you think about it, the whole idea of classifying animals, which must have been invented in about the eighteenth century, that you could find a thing called ‘species,’ gave one a sort of stamp of approval on the idea that there is a natural order, there are boxes, there are shelves where everything has its so-called natural place. What is natural and what is antinatural changes with time, and is a very difficult subject. I’m thinking of offering an undergraduate course on the concept of nature.”

“But you now have the ability to create real chimeras—a human brain in a dog, or something,” I say. “This is upsetting to some people.”

“People get the heebie-jeebies when you talk to them about putting a human brain into a dog,” says Melton. “In fact, I would suggest that there are two contexts where I think there might be an interesting connection. There is something like a natural double-take when you see a person who’s seriously deformed. People mostly say, when you see a burn victim or a person who’s had an arm amputated, that the reason you’re drawn to look, or to stare, at these poor people is the fear that it could happen to you. I actually think it’s something deeper than that. I think it has something to do with an affront to this idea of the natural order of—that person doesn’t fit into this box. I hate to say this, and it might get me into trouble, but that’s what I suspect.

“Look at the literature about science,” he says. “What was the significance of Mary Shelley’s Frankenstein? Why was Frankenstein considered an important book? Certainly not in the same way we think of Harry Potter as some kind of cheap science fiction. It wasn’t just science fiction. It was, in my view, because it addressed what is the essence of being human.

“So this relates to—if I can get this back to where I started—we were talking about ES cells and why the nation is so excited about where they come from. This issue is one that I have of necessity delved into quite a bit. It would take too long to talk about the various religious views of why one should isolate ES cells and not and whether cloning should be allowed.”

“Have you written about that?”

“No, but I have to talk publicly about it often, like with Catholic priests and with the Board of Overseers of Harvard. So I actually have educated myself quite a lot on the various religious views. I don’t really want to get into it, and the reason is I don’t think it’s fundamentally interesting. It largely has to do with the trivial concern of trying to put a tag on when life begins. What I do think is deeply interesting is this issue of chimeras. So bear with me for a minute on a couple of very broad themes that I think human ES cells opened the door to.”

I nod as he shifts from biologist to impassioned philosopher.

“Let’s say that, at a minimum, there are two areas of behavior in which our government spends an enormous amount of money. Both of them indirectly struggle with the question of whether phenotypes for the final product is a consequence more of nature or more or nurture. One of these is public education. So if you think about the whole philosophy of it, the idea which I think is a commendable one is that everyone has equal potential, and given equal opportunity will produce results. The other has to do with criminal behavior. I heard on the news this morning that for the first time now, two million people—one percent of our population—is incarcerated. It’s a number I find fascinating.

“In the book Madness in Civilization, by Foucault, he says that one way to characterize a society is to hold a mirror up to it. And that mirror is, who does the society contend is nuts? It’s a very interesting thesis. You learn more about the reflection of a society not by talking about their kings and queens and the middle class, but whom the society is fearful of. Because that defines them in a way. So if you were to accept this—and I can think of better examples—that the government spends wads of money addressing indirectly this question of nature and nurture through incarcerating people. Now, is this our genotype driving this, or our environment?

“Now bear with me as I tell you two kinds of experiments that will give hard numbers on what I’m saying. I’m not suggesting that this will answer the question. What I’m saying is it’s going to give hard, factual information that will be useful. So the first one is these identical twin studies done with humans that were separated at birth. I find that fascinating, principally because it says there’s more to the genes than you want to imagine.^* And now let’s do an experiment where we clone animals so we have twins, genetically identical individuals. And let’s take an animal that has interesting behavior. It’s hard to argue that gorillas and/or chimpanzees don’t have behaviors that are very similar to humans.

“So that’s what I want my experiment to be. To clone gorillas or chimpanzees. It’s expensive, but that’s why I introduced it with the cost we spend on prisons. And now we have behavioral tests, and I don’t actually care what the tests are. In the identical twin studies, they were ‘what’s your favorite color?’ Which is a very interesting question because it’s so meaningless and stupid, and yet the fact that identical twins had an 80 percent correlation coefficient on that, even though they’d been separated at birth, I find fascinating. So let’s take gorillas. What do they like to eat better, bananas or mangos? How do they do that test? How did they do on visual acuity?

“So what you get as a result of that is numbers, hard numbers on the extent to which behavior is modified by a gene. Now, for the more interesting experiment. We take a human ES cell and we inject it into a monkey blastocyst [the first cells in a newly formed embryo]. Now you know that if you take a mouse ES cell that is, say, labeled so all of the developed cells will be blue, and you inject it into a mouse blastocyst, you’ll get a chimera where different parts of the mouse will be derived from the injected ES cell. So it might have a blue liver and some blue muscle cells, and that’s what I mean by a chimera.”

“That’s something you do today?” I ask.

“Yes. But now let’s do it with the human ES cells into a monkey, and we make chimeras. This is different from cloning now. We’re purposely trying to make a chimera—one hundred chimeras from one hundred monkeys. And now we’re going to look through their bodies and we’re going to look to see what parts of the body the human ES cell makes. Now, there’ll be a monkey where the only thing that was made that is human is the big toe. That’s completely uninteresting; no one will argue about that. No one will say that’s an experiment you shouldn’t do. And then we’ll have a monkey with a human heart. Three centuries ago, if we found a monkey whose heart was human, people would have freaked out because the seat of the soul was the heart. Now, no one really thinks that.”

He’s talking very fast now, and I’m trying to keep up, though I think he just said that no one would object to growing a human heart in a monkey. I consider this, and decide that I am okay with this in terms of trying to come up with, say, a heart for transplant into someone’s grandmother who will die because there currently aren’t enough hearts available. But Melton is already plowing ahead with his hypothetical experiment to create chimeras out of stem cells, and I’m wondering how far he will go with an idea that is already treading close in many people’s minds to Frankenstein territory with this talk about human toes and other body parts growing on, and inside, monkeys.

“But the brain is different,” he is saying. “These days, if we’re forced to pick a body part where our soul is, we say it’s connected to our mind, which is connected to our brain. And that comes back to this idea of what is natural, because that’s a relatively recent thing. So now, we have our hundred monkeys; one of them has a blue big toe; another one has a human heart. But now the interesting part of the experiment is that we can make chimeras which have different parts of our human brains, and different parts of a monkey brain.

“And one of the first level questions we might ask is, What part of a monkey has to be human in order to have speech?” He is very animated now. “I find it really intriguing, as in the movie Planet of the Apes, to walk into a lab here at Harvard and have one of the monkeys say to you, ‘Hello.’ That makes you wonder immediately, what does this monkey think? So what you want to first know, is this just mimicry, like a parrot? And it gets back to Wittgenstein, who talked about, what is the relationship between language and thought? So you ask me what am I excited about, that’s it.”

He pauses for air, and I tell him I was with him up to the point where the monkey is linking thought and speech. “I have to admit that this would give me the heebie-jeebies,” I say. “A human brain in a monkey that is conscious, it would be a horrible freak, worse than the Elephant Man.”

“I’m not suggesting that this chimera would have the intelligence of a human.”

“But how do you know it won’t?”

“It’s an interesting question; I find it highly unlikely that this would happen. I don’t think it would. There would be just parts of the brain that were human.”

“It still sounds potentially dangerous,” I say.

“You know, people once thought cutting into the body was a sin,” he says. “Now it’s normal. That’s what I’m saying. Let me put it another way. I introduce you to a young woman, and you like her, and then I say, ‘David, she’s actually a test-tube baby.’ Would you recoil in repulsion, thinking it was unnatural? People thought this would happen. And it relates back to talking about what I said, that decades ago the heart was the seat of the soul and no one thinks that now. My point is that what we consider to be natural is largely a function of time. And that society’s increase in knowledge and practices and beliefs can have a serious effect on what’s natural. So if you look at the argument about why one should not isolate human embryonic stem cells from leftover fertilized eggs, they are conflicted by the tortuous politics in this country of abortion on the one hand, by an enormous confusion on the answer to the question, ‘When does life begin?’

“And superseding all of that is the idea of what’s natural. Natural childbirth, natural conception, natural, natural, natural. Now let me say two things to you about this. One is, what I find people don’t ask themselves about enough is, if everything is supposed to be about controlling man’s intervention, why do people take antibiotics? Because that forces people to think about, what is their idea, what is a natural event and what is man’s dominion over natural events.

“Now let me explain a trick, a kind of philosopher’s game about natural conception. If you look at the legislation that’s been proposed in most countries, they have to rule out the problem of making a genetically identical individual as a reason to ban cloning, because of the existence of twins. If you didn’t do this, you would be obliged to kill one or two twins. So they have to rule out that line of argument, because it doesn’t make any logical sense. So what they’re left with is that it’s medically unsafe, which is absolutely true. I suggest to you that this reason is really a surrogate for a fear of doing something where they don’t know the consequence, by which I mean they are afraid, and I’ll tell you why. Here’s my puzzle. Right now, in natural childbirth, a certain percentage of all natural fertilization events end in something we call ‘diseased’ or ‘abnormal.’ So if you go to MGH [Massachusetts General Hospital] over here, for a certain small percentage of all children, the child has a heart defect problem. So now let’s look ahead: Fast-forward two generations from now, and I will contend that it will be possible, by medical advances, to make cloning by nuclear transfer safer than natural childbirth. That the cloned embryos will now have a defect rate, let’s call it, of less than one percent.”

“When will that be?”

“I’m not saying this will really happen, but let’s say twenty years from now, or two generations from now. I don’t know. But here’s the point. Let’s suppose the failure rate is now below what you and I call the ‘natural birth’ rate. Here’s the puzzle. Would the government then be justified in telling the population you can no longer create children by what you and I call ‘natural’ childbirth, because the probability of defect is higher than it is by cloning?”

“But there are methods being developed where you could repair those defects.”

“That’s right. But there is another point, which comes up in my discussions at the Catholic Church: There is something I think you call ‘natural abortion’—where biology removes fertilized events by not allowing them to implant.”

“You mean spontaneous abortions, or miscarriages.”

“Yes. I have a hard time finding the number because books seem to give different numbers, but people have agreed on a surprisingly high number. If you take one hundred fertilized eggs, let’s say only 20 percent of them are going to implant and make a baby. Of the fertilization events, most of them fail. If that’s true, the Catholic Church has a major problem that they fail to face up to, if life begins at fertilization. There are thirty million Catholics in the United States. If you said that 1 percent of them tried a mating event tonight, that’s three hundred thousand. And if 80 percent of those died, that’s two hundred forty thousand deaths of souls for which they should be holding a funeral tomorrow. And when I pointed this out, they find this to be a puzzle that they don’t know how to answer. One answer is that this is God’s will, and that’s fine, but then that gets you into this really complicated business of, Is it not then God’s will to have a person like me wanting to work on human embryonic stem cells?”

5

Melton presented the chimeras and clones as intellectual “puzzles” and has no plans to implement these notions. He makes it clear that he has no interest in experimenting on humans. Yet he would not be opposed to the chimera experiments if they were considered ethical and were allowed.

I wonder whether monkeys with human brains will one day seem as normal as heart surgery does today, or whether cloning will ever actually be preferred to “natural” childbirth. Melton’s obsession with “normal, normal, normal” is an intriguing one, because normality does keep shifting with new scientific advances and has since at least the day that Prometheus gave us fire—which must have radically shifted what was “normal” those many millennia ago. Also driving the issue of what is normal is Sam and Emma, whose father wants what any parent craves—to save his children from suffering. Yet as Bill Hurlbut of Stanford asks, How far do we want to go down the slippery slope? Or, as George Whitesides has said, Is there a possible scientific path that scientists could go down, but shouldn’t—when they should just say no? When one of the gifts offered by Prometheus is simply too dangerous, or too abnormal, as Melton would say?

In this sense, Doug Melton is simply another figure in an ancient question of whose normality is really normal with new science and technology, and whose is not. Ethics aside, I have to admit to a certain curiosity about what Melton would get in his human-monkey chimera. Perhaps the beginnings of a superrace of primates unimagined even by Michael Crichton, or a few poor horrific wretches that would be true Frankenstein creatures, wandering the Earth seeking revenge against their creators.

Later, on the phone, I ask Melton again whether he sees any dangers in stem cells, and chimeras, and the like. Is there a time when he would ever say no or halt an experiment?

“I don’t know what will come of this,” he says. “On the other hand, I think it’s uninteresting to live in a society where one is so afraid of the unknown that you won’t try new things. I’ll think about the dangers, because I haven’t thought about them enough. I should think about why one shouldn’t do that experiment.”

^*In various twin studies, twins separated at birth or early in life manifested differences in how they acquired diseases and traits despite having identical DNA, suggesting that both environment and genes determine outcomes.