human gene patents

Who Owns This Body?
WIL S. HYLTON
Esquire v135, n6 (June, 2001):102.

The U. S. patent code was never meant to cover your genes, your cells, your blood, or the marrow in your bones. But it does. And Craig Venter's map of the human genome was never meant to lead to the kind of great gene rush that is taking place as you read this. But it has. And the worst thing is, it's too late for you to do anything about it. You've already been sold.

The symptoms crashed down like an avalanche, and John Moore didn't know what to think. Bruises all over his body, bleeding gums, and the roll of flesh around his waist that he'd always figured for fat had gotten lumpy and red and sore. He didn't know much about cancer, but when he finally dragged himself to a doctor in Anchorage in the summer of 1976, he learned more than he wanted to know. For one thing, he learned that he had it. For another, he found out his type was rare, something called hairy-cell leukemia. The doctor said it was attacking his spleen, so instead of absorbing aging blood cells the way a normal spleen does, his spleen was absorbing all his blood cells, cannibalizing him, swelling up in his gut and smashing his other organs against the walls of his body.

The doctor said there wasn't much hope, but Moore wanted to give it a fight. He found a specialist at UCLA and flew down for a consultation. Right off the bat, he liked Dr. Golde, who made such a point of cutting through bullshit that he let his patients call him Goldie. Moore trusted that, and when Goldie suggested that he should have his spleen taken out, he didn't hesitate. The surgery took three hours. A normal spleen weighs about fourteen ounces. Moore's spleen weighed fourteen pounds. Within a few weeks, he was back on his feet, ready for a fresh start, and Seattle seemed as good a place as any. He was just thirty at the time, broad and strong, and it wasn't long before he found a nice girl there, married her, bought a ranch near the coast, and got himself a job as a salesman in the oyster industry. He tried to forget about the leukemia, the bruises, the bleeding gums, the cannibal spleen. For the most part, he did. The only reminders were his follow-up visits to see Goldie. They seemed never to end. At first, Moore didn't think much of flying down to L.A. for his regular checkups. He knew cancer is something to keep an eye on. But after four years of it, he'd had enough. He didn't see why he had to travel a thousand miles every few months just to give blood and sperm samples. He offered to have the blood drawn in Seattle and shipped down to Goldie's lab, but Goldie said that wouldn't work. He mentioned that the price of the airfare was starting to hurt his pocketbook, but Goldie offered to pay for the flights. He brought up the fact that his folks were moving away from Pasadena and he wouldn't have anywhere to stay near L.A., but Goldie offered to get him a room at the Beverly Wilshire. Moore thought Goldie seemed mighty eager, but he agreed to keep coming down. Then, after seven years of regular visits, Goldie's nurse brought him a contract to sign. Moore looked at it awhile, trying to figure out what the hell it was. Something about surrendering "any and all rights." Moore didn't like the sound of that, so he circled the box that said, "DO NOT" consent and gave it back. But when Moore got home to Seattle, he found another copy of the contract in his mailbox. This time, it had a Post-it note attached, with an arrow pointing to the word "DO." He looked at the contract again. Again, it seemed strange. Again, he didn't sign it. A few weeks later, yet another contract arrived by mail. This time, there was a nasty letter attached, Goldie telling Moore to stop being obtuse and sign the damned thing. He didn't like Goldie's attitude. Something was fishy, and he decided to find out what. He sent the contract to a lawyer.

Moore was at home when his lawyer called him back with some news. Turned out that Goldie had a few things going on behind Moore's back. Even before the surgery, Goldie had suspected that leukemia researchers would love to run experiments on Moore's spleen. So the doctor had instructed his surgical staff to remove some cells from Moore's spleen and make a culture. Then Goldie brought the culture back to his lab and kept Moore's cells alive, kept them reproducing, a tiny portion of Moore's body living inside a dish. Goldie took out a patent on Moore's cells in 1984, and then, without mentioning it to anyone, he shopped them around to a few pharmaceutical companies, eventually finding a taker. A company named Genetics Institute offered him seventy-five thousand shares of stock, worth about $1.5 million, for Moore's cells. Moore nearly fell over when his lawyer told him about that transaction. Later, after the shock wore off, he was just plain pissed. Not that he minded his cells being used in research. He minded being lied to and treated like a sucker. He minded being invaded and ripped off. Goldie hadn't ever told him about any cell line, or any patent, or any million and a half bucks, and Moore was starting to feel like a fool. He figured his best recourse was a lawsuit. But when his case went before the California Supreme Court in July of 1990, the judges weren't impressed. As far as they were concerned, Moore didn't have any right to sue Goldie for stealing his cells because the cells didn't belong to Moore in the first place. They might have come from his body, and they might have contained his DNA, but that didn't mean they were his. On the contrary. According to the judges, Moore's cells couldn't belong to him because if they did belong to him, then Goldie couldn't have a patent on them. "Moore's allegations that he owns the cell line and the products derived from it are inconsistent with the patent," the majority wrote, adding that he "neither has title to the property, nor possession thereof" and concluding that "the patented cell line and the products derived from it cannot be Moore's property."

John Moore didn't own his own body. Neither do you. Not your body, not your blood, not even your genes. Not unless you've got a patent. And it's too late to get a patent on some parts of your body. They've already been sold. Like, for example, the gene called BRCA1. There's a chance you have that gene. There's an even better chance your wife has it, or your sister or your mom, because that's the gene for breast cancer. If you could test yourself for BRCA1 right now, or if you could test your wife or your sister or your mom, you probably would, right? Just to be on the safe side. But you can't test yourself because you don't know how, and your doctor can't test you because he's not allowed -- at least, not without permission from the person who owns the gene. And that person isn't you. It might be in your body, but it doesn't belong to you. It belongs to a company called Myriad Genetics in Salt Lake City. So if you want to know whether you have the gene for breast cancer, you're going to have to call somebody for permission. Then you're going to have to pay for the cost of the doctor's visit, plus a $2,500 fee to Myriad Genetics just to access its gene, the gene inside your body. Those are the rules of the patent game. That's what a patent means: exclusive access. And the last time somebody broke those rules, the last time somebody ran a test for BRCA1 without permission, Myriad Genetics went after them. And Myriad Genetics made them stop. And that was a university. And that's just BRCA1. There are about a thousand other human genes that have been patented. Some of them are in your body, and many of them are important, like the one for Alzheimer's disease and the one for epilepsy and the one for brain cancer. If you happen to have one of those genes, it might interest you to know that researchers are paying to access them, too, sometimes millions of dollars just to continue the work of looking for a cure.

It's not just genes, either. There's a patent on the blood inside every human umbilical cord. So if, by chance, your newborn baby needs that blood, don't expect to get it for free. There's also a Swiss company called Novartis that has a patent on the stem cells in your American bone marrow. Don't expect to access those cells if you ever need a transplant, either, unless you're prepared to pay. Some companies have patents on entire species of animals, like the species of mice and pigs that belong to DuPont. You can patent people, too, and not just John Moore. These days, you can get a patent on just about anybody; a patent issued in 1995 to the U. S. Department of Health covered the cell line of an unsuspecting member of the Hagahai tribe in Papua, New Guinea, whose resistance to certain diseases made him valuable to researchers. Other patents filed by the U. S. government at around the same time covered indigenous people from the Solomon Islands and from the Guaymi tribe in Panama. As a matter of constitutional law, all of this is highly suspect. There's never been a vote by Congress to approve the patenting of human or animal life, there's never been an executive order by any president, and there's never been a decision by the U. S. Supreme Court on the patenting of any animal larger than a microorganism. In fact, just twenty-five years ago, you couldn't patent any of it: genes, cells, blood, marrow, even a clipped fingernail. Back then, the U. S. patent code looked a lot more like the code Thomas Jefferson wrote, the code that was designed to protect inventions -- think cotton gins, whoopee cushions, Twinkies -- made on American soil. But that hasn't slowed down the patent code, which not only applies to U. S. soil but now lays claim to ninety foreign countries, and even to "any object made, used, or sold in outer space." If you're starting to get the impression that the U. S. patent laws have gotten out of hand, if you're starting to wonder how they got that way, how they stretched so wide so quickly without any public debate or government approval, the first question you ought to ask yourself is why you never thought about it before. The answer, most likely, is that you didn't know. You didn't know because nobody knew. Nobody knew because nobody cared. Life went on, oblivious. And that's how it happened.

Jim Watson saw the whole mess coming. Not at first, of course. At first, he was in awe of the biological revolution, just as the rest of the world was. After all, it was his revolution, his discovery that sparked it, his insight, made in his lab, his glimpse into the mind of God. And so, for a short while, he put aside his natural cynicism and basked in the glow of his accomplishment. It wasn't that nobody had ever seen DNA, it was that nobody knew what it was, or what it did, or even what it looked like. Microscopes had never been able to get closer than a blurry smudge, and as far as anyone knew for sure, that smudge might have been irrelevant cellular garbage. It took Jim Watson and his partner, Francis Crick, to figure out that DNA mattered. Watson might have made the discovery even sooner, but it took him a few years to get through school. Not many years, just a few. He started college at fifteen, received his doctorate at twenty-two, began his career at twenty-three, and when he and Crick solved the riddle of DNA in 1953, he was just twenty-four, a pale, gawky kid from Chicago with a long neck and a narrow head of wispy black hair. He was an ambitious bastard, too, already thinking about the Nobel prize that his work would bring. Watson and Crick had solved the first riddle of DNA. They had figured out that it was shaped like a string, or, rather, like two strings twisted together, a Twizzler-like structure they called the double helix. They had also discovered that those strings were made out of billions of tiny particles, called nucleotides, all linked together in a chain, one by one, in a very specific order.

The trick that lay ahead was to understand the precise order of those nucleotides, why they were aligned in that specific way. The discovery carried certain risks, however, the most obvious of which was that the order of nucleotides could be tinkered with, changing a person's genetic instructions and thereby rearranging his or her body or mind. Such modifications might do good in some cases, with the potential to cure hereditary diseases or deformations, but they could also take nature down a new and unseemly path. They could replace natural selection with a kind of deliberate genetic art. At the very least, it was clear from the outset that genetic science had a special responsibility, and one of the earliest voices of caution was none other than Jim Watson. By 1975, he had established himself as officially dubious, and when he arrived at the Asilomar Conference on Genetic Ethics that year, he stood before an assembly of his colleagues and announced, "We can't even measure the fucking risks." Watson was still just forty-five years old, but he was already disenchanted with his own success. Instead of pursuing fame and fortune on the cutting edge of his field, he had retreated in 1968 to an obscure laboratory in Cold Spring Harbor, New York, where he assumed the title of director and spent most of his time fundraising for the lab's endowment. In a few interviews and public appearances, he voiced contempt for the scientific community, issuing proclamations like the one he made in his memoirs: "A goodly number of scientists are not only narrow-minded and dull but also just stupid." The truth was, Watson's retreat from the front lines had left a vacuum of creative ambition. In the three decades following his discovery of the DNA structure, not a single effort had been launched to produce a map of human DNA. Such a map would be essential for the budding field of genetics to blossom. It would provide a complete list of the nucleotides along the DNA strand, making it easier for scientists to locate and isolate specific genes. Because that's not easy to do. A gene does not have a distinct shape or contour, is not even a physically independent structure. In fact, the word gene is really just scientific jargon that describes a segment of DNA, a portion of the double-helix strand that happens to produce a protein. Each "gene" starts on a particular nucleotide and ends on another nucleotide further down the strand. Since there's no dramatic marker to announce the beginning or end of a gene, and since there are roughly thirty thousand genes in human DNA, you can imagine how hard it is to locate them without a good map.

By the late 1980s, it was beginning to look as though nobody would ever draw that map. The project seemed dauntingly, if not impossibly, huge. Even with computers mapping one nucleotide per second, it would take one hundred years to finish the job. But if anything was predictable about Jim Watson, it was that he would do the unexpected, and just when he had been counted out of the game, he emerged from his twenty-year slumber. Standing before Congress in 1987, he received a hero's welcome and a starting budget of $30 million to launch the Human Genome Project, a new division of the National Institutes of Health. He predicted a complete DNA map by the year 2005. It wasn't long, however, before Watson's prickly nature caused a clash with his colleagues, most notably with a young scientist named Craig Venter. Like Watson, Venter was unusually blunt-spoken for a molecular biologist. A Vietnam vet who spent most of his teen years smoking pot and surfing the California coast, Venter had about as much respect for authority as he did for scientific convention. If anything, he and Watson were too much alike. Watson had solved the DNA riddle in less than eighteen months, and Venter was in just as big a hurry to map the human genome. He wasn't interested in plodding along, one nucleotide at a time: He was developing a way to isolate genes along the DNA strand. He had found markers on the double helix that gave clues about the locations of genes, and by focusing on those markers, he could identify the most important parts of the genome without wasting time on extraneous nucleotides. The only problem with Venter's approach was that Jim Watson didn't like it. He didn't like the science, and he didn't like Venter, and he wanted to get rid of both. But Venter had friends in high places at the NIH. His approach to DNA mapping was faster than any other, and that had value in itself. By the early nineties, the patent code had already swollen, through a bizarre series of loopholes and judicial mistakes, to cover John Moore and maybe even raw human DNA.

To the NIH, that spelled opportunity. The sooner Venter could locate genes, the sooner the NIH could patent them. And patents meant money. Big money. Money from pharmaceutical companies, from biotechnology companies, even from small laboratories hoping to do genetic research. Craig Venter meant more patents more quickly, and more patents meant more money, and that gave him a special cachet. To Watson, the specter of genetic patents only made Craig Venter more distasteful. Watson complained to NIH administrators that they were privatizing nature, and when that didn't work, he took his beef to Capitol Hill, where, speaking to a roomful of senators in 1991, he blasted Venter's work as something that "could be run by monkeys." Venter and the NIH fought back, saying Watson was old news, old science, and that patents were the future of biotechnology. Heads butted and ideals clashed in a battle that history will remember as the inevitable conflict of two brilliant, unharnessable minds. But in the end, it was either Venter or Watson, patent or no patent, and in April of 1992, Jim Watson was asked to resign from the Human Genome Project. He returned to the Cold Spring Harbor Laboratory to resume his duties as director, the man who had unlocked the secret of DNA, who had led the charge to decode it, pushed aside by the commercial forces that would eventually consume biology. "What is this? It looks like an artifical anus." Craig Venter is grinning now. His tiny eyes gleam beneath the tangled mass of eyebrows that protrude like fingers from his brow. He is mostly bald, with a friar's ring of hair grown longer than most men would dare, and he's running a hand over the dome, looking at a record cover with a picture of a trumpet mouthpiece on it. "Uuunngh," he grunts, tossing the record aside.

This is Craig Venter, fifty-four, the man who mapped the human genome and who has been accused of attempting to own it, the man who left the NIH in order to compete with it, the man who has been called the "next Hitler" and who has, more than anyone else in the world, become the face of gene patents. This is Craig Venter at work, slung back in an executive chair, with his bare ankles crossed in front of him, surrounded by three black standard poodles, all barking and wrestling one another on the carpeted floor while three of his employees stand around the desk, all talking at once, to him and to one another, about three entirely different topics, with Venter listening to none of them and also to all three of them, responding occasionally to each of them, even while reading the mail and looking at the album cover and playing with the dogs and gazing out the window and generally giving the false impression that he is distracted, which he is not and rarely ever is. Someone in the room is talking about Mount Everest. Someone else is talking about antibiotics. Venter picks up a pamphlet that he commissioned to announce the completed human-genome map, the second great secret of DNA, the one he unlocked, the reason he will probably win a Nobel prize. Venter unfolds the pamphlet, turns it over, then back. "Do I have any spare time tomorrow?" he asks an assistant who has, until now, been talking about a symposium in Europe. She pauses, switching gears. "It's going to be a crazy day." Venter shrugs. "They're all crazy." He tilts an ear toward a publicist on the other side of his desk, who has switched from the subject of Mount Everest and has begun prepping Venter for an upcoming press conference. He listens for a moment, then turns back to the assistant. "See if we can make time to call Umberto Eco," he says. "Just to make sure he's going to be at the symposium." Refolding the pamphlet, he turns back to his publicist. "Who's going to be at this press conference?" he asks. The phone is ringing. His cell phone. "People like The Guardian," the publicist says, raising her eyebrow as she says the name of the left-wing British newspaper. The British press has been especially hostile toward Venter. "Why would I want to talk to them?" asks Venter, reaching for the still-ringing cell phone. "Well ..." says the publicist. A senior researcher steps into the room, a short man with neatly parted hair and a perfectly trimmed mustache. Venter nods hello, yanks the phone from his hip, but doesn't hold it to his ear. "Okay," he says to the publicist as the researcher returns his nod. Venter wags the phone like a scolding finger. "I'll talk to the assholes, but you're coming with me." The researcher smiles, acknowledged. The publicist sighs, exasperated. "You're going to have to clone me," she says. Venter on the phone: "Hello? Yeah. Just put in the estimation. The average accuracy. 99.96. Yeah, percent." Lowering the phone to his thigh, he hands the pamphlet to the researcher. "Hey, check this out." Then to the assistant, "Who's this guy from Disney speaking at the symposium?" Back on the phone: "Sure, and Jim said there's a listing in the table that there's no yeast seven transmembrane receptors." The researcher looking at the pamphlet: "Cool." The assistant shuffling papers: "I printed out his bio." On the phone: "That's a mistake. There are at least two in yeast." The dogs barking, Venter squinting his eyes, reaching under the desk to grab one of them by the snout while still on the phone, saying, "There's yeast-mating factor," the assistant digging for the bio, the researcher reading the pamphlet out loud, the publicist asking the assistant questions, the dogs breaking away into another snarling roughhouse, the desk phone beginning to ring....

Outside the room, stillness. Silence. The atmosphere you might fairly expect from a giant white building in a just-built Washington, D. C., suburb known as the Technology Corridor. There is the scent of detergent, of plastics and paint. Clean, whispering fluorescent lights. Prim young women and men walking briskly down the halls, giving artificial smiles and officious little nods to one another. It could be a law office or a dentist's waiting room except for the glass tunnel at the far end of the hall, spanning a landscaped garden, leading to one of the largest civilian supercomputers in the world. He built that thing over there. He left the Human Genome Project in 1992 to build it. They wouldn't build it for him, so he built it for himself. His own human-genome project, his own genome processor, his own goddamn institute of health. Floor after floor of microprocessors, hard drives, alpha servers, you name it, all linked together, firing and rifling through more than 100 terrabytes of memory. This is Celera Genomics, Incorporated, the hardware of Craig Venter's imagination.

Because his imagination needed more room to breathe. Because the government computers were too small, and so were the government minds. Because they had liked him early on, until he needed more funding, more machines, more power. Because nobody--not even a fellow maverick like Jim Watson--believed him when he said there was a way to automate and accelerate the whole process. Because there were plenty of computer experts in the world, and plenty of mathematicians, and there were plenty of molecular biologists, some better in the field than he. But he was the one with the capacity to juggle all those fields in his mind, the algebra and biology and computational logic and probability and industrial sequencing, to keep all those mix-matched balls in the air long enough to see how they moved together. He was the one who drew inside and outside the lines of all those disciplines, who understood that a big enough computer and exactly the right algorithm and the forces of probability and logic and statistics could mesh together, allowing the computer to do the work for you, could let you sit back and drink a margarita while the human genome cracked open.

Maybe he didn't wire the supercomputer himself. And maybe he didn't write the software. Maybe he didn't devise the combinatorial algorithm for the data. But he was the one who woke up sweaty with the vision bashing through his skull, the train wreck of all those disciplines yielding an epiphany in the night: The human genome could be mapped in less than one year's time. That's why he left the government project, and that's why the line formed behind him: a Nobel laureate named Hamilton O. Smith; some of the world's foremost computer-science geeks, including Gene Myers, the preeminent author of DNA-sequencing algorithms; even the director of the National Cancer Institute, Samuel L. Broder, all dropping out of their respective limelights, out of their various prestigious gobbledygook to form a technical-support group in Craig Venter's lab. It wasn't the money that brought them. Money never could. Besides, the moneymen were right there in line with the rest of the hangers-on, all clinging to Venter for the same reason: They bought his vision and wanted to see it happen. Now Sam Broder stops in the glass passageway to explain why he did it, why he left one of the most coveted positions in the scientific world for this. A little man with downturned eyes and a faint, squeaky lisp, Broder is more the proper image of a biologist than his boss is. "When I read in the newspapers that Craig was going to do the human genome," he says, his round eyes blinking proudly behind dense glasses, "I said, I've gotta do this. It was one of those areas where I knew that I would regret it the rest of my life if I didn't. Ten years from now, I would've looked back and said, I should've done it. The truth is, you can't go back. You don't get a second chance. I said to myself, I gotta do this. I gotta do this, because if I don't do it, I'll hate myself later." Broder stops, smiles, gulps. His eyes are misty. "He's a genius. You can tell right away when you meet him. From the way he is. He's fearless. He's not like most scientists." Another employee enters at the far end of the passageway, and Broder's eyes dart to the floor. He waits for the man to pass, then looks up again. "You know, Craig gets a lot of criticism." A vaguely defiant smile, lips pressed together. "There have been people with very weird ideas about him, but I think in his heart ..." The voice trails off again. "If he had stayed at the NIH, his enemies would have slowed him down," Broder says finally. "So now we have to be a business to do the science we want to do." The business of science is not exactly a thrill sport. Not to most people. Most people, for example, probably weren't paying very close attention when the Plant Patent Act was proposed in 1930. Most people were probably more concerned about, oh, say, the Great Depression than a law that would allow botanists to patent plants. But in Congress, the bill was a subject of fierce debate. This was about more than just plants, after all. At heart, it was about patenting life, and that required some consideration.

Until that point, living things had always been off-limits to the patent code, if for no other reason than that they were products of nature and products of nature cannot be claimed as inventions. For example, while it's okay to patent a method of purifying tungsten, it is not legal to patent the element itself. Tungsten is not an invention. The same had always been assumed about plants, but by 1930, the distinctions were beginning to blur. After all, nature may have invented the rose, but it certainly never produced the Betty Prior Hybrid Polyantha, a full-bodied rosebush that was bred for its resistance to disease and cold. Congress wanted to reward growers who were developing new strains, but it also knew that patenting plants was the beginning of a very slippery slope. You could start with the best intentions, but if you weren't careful, if you didn't pen the letter of the law just right, you could grease the way right down that slope into bizarre new territory-the patenting of hybrid insects, perhaps. Maybe even mammals. Maybe people. To make sure that didn't happen, to plug any possible loophole in the law, Congress revisited the Plant Patent Act in 1970, adding a clause that specifically excluded bacteria. It had taken lawmakers forty years, but they had drawn a clear boundary on life patents: A plant could be seen as an invention, but other organisms could not. Two years later, a scientist from General Electric showed up at the U. S. Patent and Trademark Office with an application for "a bacterium from the genus Pseudomonas." The application was quickly rejected. But GE wouldn't take no for an answer. As far as the company was concerned, the Pseudomonas bacterium was not just any bacterium; it was an invention, just as much as any hybrid rose. It had been genetically bred in a laboratory, did not exist in nature, and had a commercial function: It could eat oil out of salt water and could be used to clean up oil spills. GE decided to sue the patent office in hopes of changing the decision. The courtroom was nearly empty when that case went before the U. S. Supreme Court on Saint Patrick's Day in 1980. The business of science is not exactly a thrill sport, and the national press was nowhere to be found. Arguments were brief and to the point. General Electric insisted that, no matter what the patent office said, its bacterium was an invention and should be protected by the patent code. The U. S. Patent and Trademark Office countered that, in spite of General Electric's marvelous bacterium, the laws of the United States were a clear and final authority that said bacteria were not patentable.

The decision that emerged from the judges' quarters nearly three months later would usher in a new era in American patent law. "The fact that microorganisms are alive is without legal significance," the majority wrote. "Respondent's microorganism plainly qualifies as patentable subject matter. His claim is not to a hitherto unknown natural phenomenon, but to a nonnaturally occurring manufacture or composition of matter--a product of human ingenuity having a distinctive name, character, and use." Not only was the U. S. Supreme Court overruling Congress with its verdict, it was also overruling the U. S. Constitution, which states that only Congress has the power to change patent laws, a detail noted by Justice Brennan in his dissent: "It is the role of Congress, not this Court, to broaden or narrow the reach of the patent laws," he wrote. "Congress specifically excluded bacteria from the coverage of the 1970 Act." Still, the majority had ruled, and the GE patent became official on a hot summer day in 1980. Here was the future, laid bare. Here was the Supreme Court making it legal to patent not only a bacterium but a whole new species of them. Here was the Supreme Court declaring a species of animal to be an invention. Here was the Supreme Court writing a new definition of life. Not that most people noticed or cared. Not that most people were even paying attention to the business of science. Not that a microorganism really counts as an animal, anyway. Not like it was a monkey or a fish or a mouse.

Jeff Green built a better mouse. Or, to be precise, he built a worse mouse, but he did it on purpose. He invented a mouse with cancer. "What we did was overexpress oncogenes," he says, standing slightly stooped in a white turtleneck and faded black jeans, his longish brown hair and beard just unkempt enough to appear professorial. "We developed the first transgenic mouse model for prostate cancer doing this, and it turned out that we also developed an excellent model for breast cancer." He's standing in a tiny government office on the campus of the National Cancer Institute in Bethesda, Maryland, an underfunded and overcrowded laboratory with research supplies stacked on the floors and counters. Behind him, there is a cartoon of a man holding a sign that says, WILL WORK FOR HEFTY SALARY AND PRE-IPO STOCK. At his feet is a small cardboard box. He reaches down to pick it up. "I think there might be one in here," he says, shaking the box lightly near his ear, setting it on a countertop and popping it open. A fat white mouse is inside, lying on its stomach, legs spread, with a peanut-sized hump on its shoulder. It doesn't move. Not a whisker. "Okay, so she's not very active," says Green. "But can you see that lump? That's a mammary gland. It's a female. This is what one of our mice looks like after the tumors progress." He studies it some more. "This animal is probably five or six months old. She's close." Closing the box, Green takes a deep breath, sighs, and squares his shoulders. "We've essentially generated a new kind of animal," he says. "We've changed the genetics in a very defined way, so now we can breed these animals and predictably get the same kind of cancer in later generations. That's why it's a powerful tool; you don't have to go back and generate it again. It becomes incorporated into their genome." That's the upside: that Jeff Green has plenty of mice with cancer, which is helpful when you study cancer, because mice get sick and die in a way that's similar to the way humans die, so if you watch the mice deteriorate, you can learn something about how cancer works. The downside, the thing that Jeff Green can't quite understand, is that somebody else already owns his mice, that somebody else has a patent on them, that even though he invented the mice and even though nobody has ever created mice quite like them, the mice are not his property and he cannot legally use them in his research because they belong to somebody else. That somebody is Philip Leder, a genetic scientist at Harvard University. In the early 1980s, Leder invented his own cancerous mouse and named it OncoMouse. Much like Jeff Green's mouse, the OncoMouse had an overexpressed oncogene, and, also like Green's mouse, it got cancer. Those are the only significant similarities between Jeff Green's mouse and Leder's OncoMouse. They do not have the same genetic mutation or the same genetic code, they are not the same subspecies of mutated mouse, and they do not get the same type of cancer. But Leder was clever when he invented the OncoMouse. He knew that a few years earlier, GE's oil-eating bacterium had been patented and that the Supreme Court decision had left room for larger animals, so when Leder applied for the patent on the OncoMouse in 1984, he stretched that loophole to the limits. His attorney wrote the patent application so broadly that it covered not only the OncoMouse itself, a specific genetic creation, but also every other "non-human mammal" with an overexpressed oncogene. In an earlier era, Leder's bloated patent application would almost certainly have been denied. But at the time he filed his application, the U. S. Patent Office was still reeling from the GE bacteria verdict, revising its laws, struggling to figure out where to draw the line on animal patents, and, somehow, in the midst of the confusion, Leder's patent was granted. Now it was possible to patent not only a species of bacteria, not only a subspecies of mouse, but even a group of animals that wasn't in the same species, or even the same genus. Leder's patent was so broad that, in addition to covering mice, it also covered pigs, horses, monkeys, cattle -- anything with an overexpressed oncogene. So broad that it covered Jeff Green's mice, the first mice with prostate cancer, before Jeff Green even invented them. Before they even existed.

Now, all things being equal, Leder might have been willing to let it slide, since he's generally a nice guy and since, after all, Jeff Green works for the government, not for profit. Problem was, by the time Green invented his mouse, Leder had already licensed the OncoMouse patent to DuPont, and DuPont wasn't eager to extend any professional courtesies to Jeff Green or the government or anybody else. DuPont wanted to charge fifty dollars for every animal ever created or born with an overexpressed oncogene, and they had a legal right to do it. "The mouse we made technically falls under that patent," Green shrugs. His work, for years, has skirted the law. If he had discovered a cure for cancer, the cure would have belonged to DuPont. Because the government didn't have permission to use those mice, didn't have permission from DuPont to continue with cancer research. Fortunately, says Green, just last year, after years of haggling, DuPont finally gave the government permission. Now the government can use mice for cancer research without being sued by DuPont. Now the government can, but a lot of research companies still can't. "Other drug companies will stay away from using these mice," says Green. "If they use this technology or animals that were generated with this technology, then DuPont may have a legal right to their work." He shakes his head and laughs a laugh of disbelief, of polite disgust. "It would be nice if the system was revised." The first time you ever heard John Moore's story, he was sitting at a bar in Seattle, telling a tale about a doctor stealing his cells, and you gaped at the sheer audacity. Now you know enough not to be surprised. Now you know about thousands of doctors and companies and government agencies doing the same thing, or worse, all clutching at Craig Venter's human-genome map as if it were a guide to pirates' treasure. What amazes you now is not the patenting itself; it's that the whole thing passed you by, that life was being parceled out while your life went on, oblivious. But one man has been there through it all. Before Craig Venter mapped his first gene, before the oil-eating bacterium went to court, even before Jim Watson's big return, one man was keeping an eye on the business of science. He is a small and aging radical with a few tricks still up his sleeve, and you find him in his tidy office at the Foundation on Economic Trends in Washington, D. C., near Chinatown, a buttoned-down and squared-away old yippie with a neatly trimmed mustache and a cheap gray suit. "Okay," he says, jumping up from behind a desk to shake your hand vigorously. The words come quick, in bursts. "Have you read The Biotech Century? What have you read? What do you think?" The bookshelves, pressed against the wall of the adjoining room, are lined with his books. The first, Who Should Play God?, published in 1977, predicted things like surrogate wombs and test-tube babies and the commercialization of the gene pool, things that sounded absurd at the time, so absurd that Jeremy Rifkin quickly earned a reputation as an alarmist. Now he is taken more seriously. Now he speaks on the radio and wears suits to the office. Today, he has just returned from the World Economic Forum in Davos, Switzerland, where he was a featured speaker. "There's a philosophical issue here that's the deepest of all issues, but it's never talked about," he says. His voice is narrow and thin and high. "In the last century, we fought over whether you can have a human being as property. Slavery. We abolished it. The Thirteenth Amendment." His eyes are dark and wide, his hands small. He spreads them. "So you can't own a whole human being, but now you can own all the parts. Genes, cells, chromosomes, organs, tissues, and whole organisms. What happens if we patent all the building blocks of life? What role is there for faith and theology, or even a concept of nature as being independent and a priori? What happens if kids grow up in a world where the government says life is an invention?"

But the truth is that these days, even Jeremy Rifkin is saying that life is an invention. These days, even Rifkin is playing within the system. After twenty years of agitating against the business of science, he has learned that the way to slow its momentum is not by protest but by patent. He has seen the power of DuPont's OncoMouse patent, its potential to slow down research on prostate cancer, and he has seen the power of Myriad Genetics' patent on BRCA1 and how it could slow down research on breast cancer, and seeing that power has given Rifkin an insight: It's the same power he wants to wield--the power to stop power. And so in 1997 he applied for a patent on all human-animal hybrids, a patent that would give him the exclusive right to determine who can mix human and animal DNA, the next frontier of genetic research. Already, it's a frontier in fast development. There's a company called Nextran mixing human DNA with that pigs, hoping to mutate pig livers into something a person could use. There's another group of scientists at the University of Bath in England experimenting with frog DNA, hoping to create sustainable systems of human organs that can be harvested for transplants. Rifkin's patent would cover both of those experiments, and he would wield his patent like a weapon, stopping anybody from doing any research whatsoever with human-animal hybrids. So far, the prospects for his application don't look promising. Actually, it was denied last year. But to an agitator like Rifkin, rejection is where the fun starts. "We have a challenge in the patent office now," he says eagerly. "Then it's going to the Patent Board, the U. S. Court of Appeals, and then probably the Supreme Court." Outside, traffic is moving down the busy street, but you can't hear it, and you have to wonder if anybody out there can hear Jeremy Rifkin. Or if anybody would hear him even if they could. If they even should hear him now, talking about his rejected patent and his efforts to force it through. Life is being parceled out while, at the same time, life goes on, oblivious.

Outside, traffic is moving down the busy street. Inside, even the radicals are filing patent applications. It would be hard to find something more unpatentable than a gene. Genetic materials do not meet the criteria for a patent. They are not new; their function, for the most part, is unknown; and while it may be true that some living things, like the OncoMouse or the Pseudomonas bacterium, were invented by humans, the same cannot be said about the one thousand human genes that have been found in nature and patented that way. They are, in the words of the Supreme Court bacteria decision, "a hitherto unknown natural phenomenon," which should make them unpatentable, like tungsten. They just don't fit the specs. And yet, in the race to privatize life, the fact that genes should not be patentable makes them all the more important to patent. They have become the ultimate symbol: If a gene can be patented, anything can be. And so the bricks of life have come to mark the end, not the beginning, of the slippery slope. The great irony of all this is that most of the early patents on genetic data were not filed by big business at all but by the government's Human Genome Project in 1992. And Jim Watson wasn't the only one to protest. The biggest opponent at the time was the Industrial Biotechnology Association, a consortium of private companies concerned about the effects gene patents would have on the flow of knowledge and research. It was only after the NIH defended gene patents that big business jumped into the game. Even today, one of the most prolific patenters of human genes is the NIH. But big business is fast catching up. Companies like Incyte Genomics and Human Genome Sciences have filed for patents on hundreds of thousands of DNA sequences over the past five years, mostly on random patches of DNA that may or may not even contain genes. Incyte alone has applied for patents on more than one hundred thousand partial gene sequences, just hoping that somewhere along the stretch of DNA they have claimed there will be a few useful genes that they can hoard for themselves or sell. There will surely be money in licensing genes to researchers, but nowhere near the windfall these companies will collect when one of "their" genes is used to cure a disease like cancer or cystic fibrosis or Alzheimer's or Parkinson's or Huntington's, all of which are associated with patented genes.

To get a sense of just what these patents may be worth, you don't have to look any further than the reports of investment banks. "We maintain our long-term buy on Incyte," says J. P. Morgan's equity research report. "Given its early position in gene finding and patenting, and genomics databases, it has carved out a large, very valuable, and largely irreversible position." Or Robertson Stephens on Human Genome Sciences: "HGS has one of the broadest portfolios of protein targets in the industry ... and an impressive patent estate to protect its discoveries. This translates into one of the largest intellectual property positions in the industry." In fact, the one genetics company that doesn't brag about its patent collection is the company you'd probably expect to have the biggest collection of all: Celera. But the fact is, Craig Venter doesn't hold any gene patents. Not one. There was a time, a few years ago, when he did, when he applied for and was granted provisional patents on several thousands of gene fragments he had discovered. But they expire after one year, and Venter never upgraded them into full, twenty-year patents. He does plan to hold patents in the future, but the number of genes he'll patent will be in the low hundreds, not the hundreds of thousands like his competitors. He'll patent just the genes he wants to research himself so he won't have to pay a competitor for access. But, for the most part, patents aren't important to his business plan. Venter's goal is not to own the genes or even to provide access to them. His plan is to offer the best available analysis of the whole DNA strand, a running stream of information and insight, much like a trade magazine. Subscribers to his service won't get access to patented genes; they'll be exposed to a fresh collection of ideas and the most complete data available, including comparisons between the human genetic code and those of several other species. Venter thinks of gene patents as a necessary evil, away for researchers to recoup their financial investments without keeping their discoveries secret. "Patents are not secrecy," Venter says. "The patent law is basically there to encourage people not to hold trade secrets. When you patent, the information gets published." But the reason Venter has become a lightning rod in the growing debate is not because of his specific point of view or because he holds any gene patents. It's because he's one of the only people in the private sector who's willing to debate the issue at all. Actually, he's more than willing, even more willing than many academics. He's eager to engage the debate over gene patents, gene testing, gene discrimination, and anything else genetic. Because he's sick of hearing the eggheads do all the talking, and he's sick of the mentality that the business of science should be kept under wraps. He wants the public to know what's going on in the biotech revolution, and he wants to have an open debate about it, to confront not only its promises but also its threats. And so Craig Venter may be the only person in the whole field of genetics who's hungry for that discussion, who's so anxious to get a lively debate going that he's willing to fly around the world, often on his own tab, just to fan the flames. Tonight, you can find him in the Gothic marble admitting room of a five-hundred-year-old hospital in France, a room that has been filled with a dozen round tables, each one holding ten place settings. His flight arrived from D. C. this morning, and he's flying back tomorrow morning, and it's been thirty-six hours without sleep so far, maybe a few more, which means that Venter, who is famous among his staff for being indefatigable, is just now starting to get tired. You can see the day in the droop of his eyebrows, less wild and lively than usual, sinking and then jerking back up, snapping to as he twirls his spoon around in his three-fish soup and tries to make conversation with his tablemates. He's been a celebrity all day at a conference on genetics in Lyons, surrounded by a sea of autograph seekers, and he's brought a CD-ROM to the event tonight. The cover has a picture of Da Vinci's man and says "The Human Genome Map." The disc inside is blank. Venter's planning on leaving it behind at the end of the night, just to mess with the mind of some dummy.

He's finding ways to amuse himself, but he looks bored tonight, in an expensive blue suit that couldn't possibly fit worse over his slouchy, disinterested frame. The painkillers he took this afternoon have worn off, no longer blunting the edge of his exhaustion, and although he asked around for some pot, he wasn't able to find any, so he has been forced to rely on wine--the third bottle's almost empty--which is muting the pain but, unfortunately, dulling his wit as well. He's fading. He's drifting. He's something that Craig Venter rarely is: shot. Suddenly, a voice comes blaring through the speaker system, and Venter snaps to attention. "Now that we've fed the senses in this beautiful hall, and we've fed the stomach, we come to feeding the mind and the imagination," the voice announces. Venter wipes his eyes, trying to spruce himself up. "We've got a really wonderful lineup of contributors this evening. We have Denis Hochstrasser, from the University of Geneva, a pioneer in proteomics. We have Jean-Marie Lehn, a Nobel laureate based at the College de France in Paris. We have Gert-Jan van Ommen, from the University of Leiden. And we have a bloke who I'm not sure if anybody has ever heard of, Craig Venter from Celera Genomics. So I think it's a great group of people to get together and kick some ideas around." Hearing his cue, Venter rises, shuffles to the front of the room, and climbs on stage where the other scientists are converging, greeting one another with niceties. Venter gives them all a quick nod, then flops down in a chair, shifting uncomfortably in his seat as each member of the panel introduces himself with a long-winded autobiography and a personal mission statement. Venter can barely suppress his yawns, and when it's his turn to make an opening statement, he leans into the microphone and mumbles, "Well, I've consumed a lot of wine, and I want to make sure I save some comments for later," then he leans back, done. A flurry of hands leap from the crowd with questions, and the moderator invites a young man to be first. "I'd like to address a topic to anyone on the panel," he says, "and that's the issue of ownership versus free access." Venter rolls his neck, reaching for the microphone. This is what he was hoping for, a lively debate, right from the start, something to help wake him up. "I think it is a difficult challenge in terms of deciding where to draw the line," he says, "and I think the legal system has been slow to respond to the front lines of science." "Would you say that certain segments of the genome are not available to everyone?" the guy asks. Venter shakes his head. In a few days, he will publish the entire genome map online; anyone will be able to see the nucleotide sequence for free. Anyone will be able to see the collection of all human genes, including dozens of new, unpatented ones. Of course, the patented genes will still be restricted in commercial research, but there will be no secrets about where or what they are. "No offense," Venter says, "but that's the number-one fallacy I hear from people. When you submit a patent application, it gets published by the patent office. Patents are the opposite of secrecy." At that, van Ommen leans forward, the spitting image of a young Einstein, with his brow in a bunch. "But patenting does create problems for the scientist," he says in a thick Dutch accent. "When you find something, you want to publish it in Nature right away, but you can't. You first have to call a patent lawyer." Venter gives him an annoyed look. Van Ommen raises his eyebrows. Venter takes a sip of water. The debate is under way. Another guy stands up in the audience, asking why Venter won't publish his DNA map, with some analysis, in a scientific journal. Venter assures him that he's got an article in the upcoming issue of Science. There's a young woman from Glasgow who's worried about the prospect of genetic discrimination, and Venter nods, saying, yeah, it's a concern of his, too, that he's lobbying Congress in the U. S. to set a global example with some kind of bill to stop genetic discrimination before it starts. There's a guy who wants to know how hospitals in the Third World will ever be able to afford the licensing fees to screen for patented genes, and Venter says it's a fair question, reminding the crowd that he doesn't hold any patents himself, but admitting that he thinks companies should create a flexible pricing system, offering better deals to poorer nations. But just as the discussion is really starting to roll, a man stands up in the center of the room and brings it to a quick end.

"My two children suffer from a rare disease," he says. "I'm just a father. I got involved in this four years ago. I started a research foundation." His voice cracks. He catches himself, gives a slight smile. "I'm nervous," he says, swallowing. "Anyway, we found the gene, and we cloned an animal model." His voice breaks again. Again, he catches himself. "Whew," he says. "My hope and my expectation is that I will save my children's vision loss, and the six thousand other patients' that I represent. And I think it's just ... I think we all kind of get buried in the minutiae of patents and so forth, and I think it's important to recognize the power of this technology to solve and to protect human existence. We have to remember to think positive thoughts and focus on the difference this technology can make in people's lives." Silence. A cough splits off the marble walls, and for the first time today, all eyes are off Venter. The moment lingers, the room hushed in support of this speaker, this father, this man announcing his hope, his calm confidence that genetics will better the world. The room is still, and Venter endures it as he has endured the stillness and silence for so long. As we have all endured the blind optimism that allowed business to consume science, that allowed life to be parceled out, even as life went on. Oblivious.