Wired, Feb 2001 (You)2 Human cloning has always been frightening, seductive - and completely out of reach. Not anymore. By Brian Alexander ----------------------------------- In four hours, the Creator will ask me for $100,000 to help finance the cloning of a dead man. But by then, he'll have swallowed too much alcohol, driven us recklessly around the city in his sports car, and tried and failed to pick up a waitress. So I'll be accustomed to a little flamboyance from him, and his strange request will seem like ordinary conversation. Right now, though, we're just starting dinner when he spells out his desire to be the first scientist in history to clone a human being. "This will be the biggest leap for mankind," he says. "It is the central core of Christianity, the resurrection of Jesus, the promise of eternal life!" The Creator, an intense, dark-haired man in his thirties, looks a little like Peter Lorre in The Beast With Five Fingers when he says this, so I have to remind myself that he's not a nut. He's a real scientist, a pretty good one, too, with a PhD in molecular biology, a list of peer-reviewed publications, and a research job at a big-name university. (Where, he says, he would be fired instantly if he went public with his human-cloning plans - hence his demand to remain anonymous.) The Creator conducts research on a protein that he was the first to identify, one that could have a tremendous impact on cardiovascular disease. Tonight, he's not thinking about this work. Tonight, he's excited - thrilled, really - by the prospect of cloning a person. "This is the easiest thing you can do! You just get the damn nucleus, and put this damn nucleus into this enucleated oocyte, and pray to God something happens, and put it back into the surrogate mother, and wait. The easiest thing we could do right now, believe me, is to damn clone a human being!" Other scientists have told me similar things, so I know it's plausible. Still, I'm skeptical that the Creator will get there first, because he's sounding a little too much like Richard Seed with this riff, too evangelistic and frenzied. Seed, you'll recall, was the retired veterinarian and physics PhD who gained brief notoriety in early 1998 by declaring his intention to clone humans and make us one with God, like so many seraphim. Unlike Seed, the Creator has some of the skills necessary for cloning a human - namely, an advanced knowledge of cell biology and the ability to cultivate cells. He has never worked in cloning, but he has spent a great deal of time thinking about it. As a postdoc in 1990, long before the 1996 birth of Dolly the sheep - the first clone of an adult mammal - he correctly visualized how to remove the biggest obstacle to adult cloning: getting cells to revert to an embryonic state. His idea was to force cells into a kind of stasis before injecting them into eggs - the technique eventually adopted by Dolly's scientists. Davor Solter, a renowned cell biologist then at Philadelphia's Wistar Institute, tried to pull off such a reversion in the early 1980s, failed, and declared it impossible. The Creator tells me he knew Solter was wrong and tried to convince other researchers to take him into their labs. "They did not believe me because they had a paper by the very well-established scientist Davor Solter," he laments, "and who the hell was I?" He reaches over his plate of shrimp to hand me a copy of his old research proposal, along with the polite brush-offs he got in response. This is proof, he says, that he was the real visionary all along. Now he wants his moment. The Client may give him a chance to seize it. A businessman living in Western Europe, the Client lost his son to disease more than a year ago, but he had the foresight to keep tissue samples from the body. Following leads picked up from the human-cloning underground - an evolving worldwide network of people who communicate mostly online and who desperately want to see cloning happen - the Client contacted animal-cloning scientists to learn how these tissues should be preserved to yield usable cells when the time comes. Based on the experts' advice, he had tissue stored in both liquid nitrogen and paraffin blocks. Then the Client cruised the underground until he found the Creator. When I call the Client, he's angry because he thinks the Creator revealed his name to me. He's obsessed with staying in the shadows, so I have to assure him several times that I found his name another way, and that I'll protect his identity. Eventually he confirms that, yes, "there is a plan. We are definitely going to proceed. We intend to go ahead. We are literally going to have our son back." The plan goes like this: The Creator and the Client will fly to an in-vitro fertilization lab in one of Asia's largest cities, in a country that has no legal ban against cloning humans. The Creator says the lab's director is on board, and is skilled in the handling of human eggs and the IVF manipulations that closely resemble those used in cloning. The procedure will work like so: Nuclei will be taken out of eggs obtained from the clinic's regular donors. Then, in a process called somatic cell nuclear transfer, the son's cells will be injected into the eggs. The eggs and cells will be fused together, and then the eggs will be activated to begin cell division. These embryos will be implanted into five to ten surrogate mothers in the hope that an egg will take hold and develop into a clone of the Client's son. All of these things are technically possible: There are no barriers except the cash, the will, and the trial-and-error experimentation. But the Client is skittish about telling me when the procedure will happen. He thinks any exposure could doom his son forever. "Everything will be seen to," is all he'll say. In a series of follow-up calls, he keeps asking me to phone another time, until finally he tells me not to contact him again. But before hanging up, he says something that gives me a satisfying chill: "It will be a big bang all around the world when it happens." That's for sure. And when we finally hear that bang, it's liable to come from somebody like the Creator, a self-starter with just enough skill to make human cloning work. The fact that society generally frowns on the idea doesn't mean it won't come to pass - it just means it will probably happen secretly, at least the first time. "People tend to step up to the challenge when there have been so many proclamations not to," says Mark Sauer, a renowned IVF doctor at Columbia University, who is sympathetic to some forms of human cloning, like making duplicate human embryos for IVF patients. "It attracts a cavalier spirit that worries all of us." The Creator's spirit has been awakened by the historical moment we're in right now, a convergence of under-the-radar pro-cloning agitation, falling taboos, and the inexorable march of science. These spheres are overlapping so neatly that "human cloning could be done tomorrow," says Alan Trounson, an animal cloner and IVF clinician at Australia's Monash University. Whatever happens with the Creator's attempt - in the months that follow our initial meeting, he and the Client begin to bicker over whether the Creator can guarantee success - his plan illustrates why producing a human clone is imminently possible. He attracted a customer who believes cloning is a legitimate course of action. He found this client through a network of like-minded people who cruise the Internet looking for one another and for the latest scientific information on the subject. He located an IVF lab that could do the work. And he's not the only one. The Raelians, a Quebec-based New Age religious group, have received reams of press around the world for their ambitious human-cloning project, called Clonaid. Late last year, they announced that they've found an American couple willing to pay $500,000 to clone their dead baby. Whether it's truth or hype - the Raelians won't provide any names or further specifics, and their story changes frequently - experts in the field are convinced that more efforts are under way. "There are probably a dozen others working on it and not saying anything," says Robert Anderson, an IVF clinician and director of the Southern California Center for Reproductive Medicine. Such attempts would have seemed impossible just four years ago. But now some people have decided they like the idea, that it's not so weird after all, especially since most individuals who seek cloning aren't looking to achieve immortality, but want to recover a terrible loss or simply have a baby. "A couple whose young boy was dying after a car accident asked me to take a cell and clone him," says Ryuzo Yanagimachi, a University of Hawaii scientist who has cloned mice. "I got a call from a girl dying of cancer. The demand for cloning is there." Don Wolf, an IVF clinician and research scientist at the Oregon Regional Primate Research Center - where he and colleagues have cloned rhesus monkey embryos, and where he's now trying to clone adult monkeys - hears frequently from infertile couples. "I have patients asking for it. I have gotten inquiries from all over the world. These are infertility patients and they are, by definition, desperate. They have no other option." People who desire human cloning have been encouraged by various mainstream writers, thinkers, and scientists. Former Microsoft CTO turned biotech investor Nathan Myhrvold, for example, has called opposition to cloning "just another form of racism," saying it amounts to "discrimination against people based on another genetic trait - the fact that somebody already has an identical DNA sequence." Conservative UCLA political scientist James Q. Wilson has said "the mode of conception, whether it's natural sex, or artificial insemination, or cloning, at least with respect to a limited set of donors, is less important to me than rebuilding the family." The pro-cloning hopefuls get a more direct kind of moral and logistical support from a nonprofit called the Human Cloning Foundation, a New York- and Atlanta-based outfit that has set up a Web site (www.humancloning.org) where people can meet and exchange information. The HCF is an offbeat group that is remarkably effective in bringing pro-cloning types together. Kathleen W., a young Florida artist and experienced surrogate mother, is a typical correspondent on the Web site, determined and ready. "If I were contacted by somebody wanting me to carry their clone, I would do it," she has told the foundation. Where there is a demand, there will probably be a supply. You can already see it: A cloning infrastructure is slowly emerging to satisfy a market that doesn't quite exist yet. Canine Cryobank of San Marcos, California, is currently storing human cells for future cloning and has told the HCF they will consider helping people who have lost "their human spouse, child, mother, father, etcetera." The Alcor Life Extension Foundation, an Arizona-based cryonics outfit that freezes heads and bodies of deceased clients for possible future reanimation, intends to spin off a company to handle cells for cloning. "We get calls all the time, and not just from our own members, asking, 'Do you do this?'" says Alcor president Fred Chamberlain. Summum, a philosophical-religious group in Salt Lake City, offers to mummify clients who want to preserve their cells for cloning. Cost: $65,000 and up. So far, 147 people have paid for the service via life insurance policies. Southern Cross Genetics, an Australian company founded by former trucking company exec Graeme Sloan, has created a co-op to help finance the cloning of human organs. But Southern Cross will help clone people, too. Eric Bleechmore, a co-op member who wants to pursue cloning, tells me in an email that he's motivated by parental grief. "My wife is 38 years old," he writes. "We had three children. Unfortunately, the two youngest children were killed in a house fire last year. They were 3 and 5 years old.... We approached Mr. Sloan about the possibility of cloning our lost children." Just as this buzz for cloning is achieving critical mass, the science needed to clone people has arrived. Cloning technology is already being integrated into important medical research. The ability to grow totipotent stem cells - the embryonic building blocks from which all the body's cells develop - is sparking a revolution. By using nuclear transfer - the essential procedure in cloning - scientists may soon be able to create transplantable tissues from stem cells to generate tissues that perfectly match a patient's. A British government panel has endorsed such "therapeutic cloning" and the harvesting of stem cells from human embryos discarded by IVF clinics. Meanwhile, animal cloning has become routine. Mice, sheep, cows, goats, pigs, even a rare Asian gaur - a massive wild ox - have been cloned. Dog and cat clones are expected to appear soon. (See "How Much Is That Doggy in the Vitro?" Wired 8.03, page 220.) Primate researcher Wolf expects to successfully impregnate monkeys with clones sometime this spring. You can now order up your own cloned cow on the Net. There have even been clones of clones, and the fundamentals are becoming rote enough that a high school girl, working at Infigen - a Wisconsin animal-cloning company - was able to clone a cow. These days, human IVF clinics use methods that are so similar to those used in cloning that they have alarmed the federal government. Steen Willadsen, an embryologist at Saint Barnabas Medical Center in West Orange, New Jersey, and the first person to clone mammals from embryos, says that some IVF technology is already "very similar to nuclear transfer." Though many people don't know it, IVF and cloning techniques have come together at least twice to create embryonic human clones. In 1998, a scientist working at Advanced Cell Technology in Worcester, Massachusetts, took a human somatic cell, inserted it into an enucleated cow egg, and started the egg dividing to prove that oocytes from other species could be used to create human stem cells. He voluntarily stopped the experiment after several cell divisions. A team at Kyung Hee University in South Korea said it created an embryonic adult human clone in 1999 before halting the experiment, though some doubt that any of this really happened. Had either of these embryos been placed in a surrogate mother, we might have seen the first human clone. All of these activities point to an unmistakable conclusion: Human cloning has become inevitable. "It will be done by someone, somewhere," Columbia's Sauer asserts. And when it's done, say experts, we'll be in for a major shock. Not because human cloning will be as terrible and disruptive as widely assumed. But because we will realize that most of our ideas about it were all wrong, that the cloning fostered by our imaginations and nightmares doesn't really exist. We'll also see that the ethical hand-wringing over the issue is anachronistic compared with other biotech dilemmas waiting just around the bend. But that's in the future. In the present, the persistent question remains: When will it happen? Nobody knows, but it could be tomorrow. Or it could have been yesterday. Michael Bishop, president of Infigen, is convinced - going only on rumor and what his gut tells him - that a human has already been cloned, we just don't know about it. "It is being done," he insists. "I have no doubt. It would be stupid and naive to think it's not." Bishop has company. Last spring, a secretive summit of animal-cloning experts was held at the Banbury Center, a conference facility at the Cold Spring Harbor Laboratory on Long Island. It attracted nearly every known animal cloner, including Dolly's creators, Ian Wilmut and Keith Campbell. Nobody other than invitees was allowed in, and the proceedings were hush-hush - no media, no tape recorders. Bishop discovered that his views about human cloning's inevitability were widely shared. "One evening after dinner, some of us were talking, and there was not one of us who believed it had not already happened," he says. "It is too easy. Too bloody easy." The idea of human cloning was not born with Dolly, though it may have seemed so at the time. We've been building up to it for the better part of a century. Animal-cloning experiments were proposed as early as 1938 and carried out in the 1950s. An alarm about human cloning sounded back in 1971, when James Watson - who with Francis Crick and Maurice Wilkins won the 1962 Nobel Prize for discovering the structure of DNA (and who now runs Cold Spring Harbor) - wrote a prescient essay for The Atlantic Monthly called "Moving Toward Clonal Man." In it, he warned that human clones were coming and that society was woefully unprepared. In 1984, Steen Willadsen cloned the first mammalian embryo, using a sheep. He was quickly followed by Neal First, a University of Wisconsin researcher who cloned a cow embryo. Dolly arrived 10 years later, and then Richard Seed announced he would try it with people. The controversy surrounding Dolly and Seed exploded so forcefully that it still reverberates. President Bill Clinton worried openly about human replicants. Dick Armey, the Republican majority leader in the House of Representatives, predicted the coming of "designer children, organ farms, and a growing disregard for the sanctity of life. This is a brave new world we must not enter." Jeremy Rifkin called cloning a "horrendous crime." The late Cardinal John O'Connor of New York evoked an apocalyptic vision of "subhuman" clone armies. "You could just keep producing and say, 'They are expendable. Give 'em a gun and send 'em out!'" After the National Bioethics Advisory Commission issued a report calling human cloning "morally unacceptable," Clinton proposed the Cloning Prohibition Act to give this statement the force of law. This legislation stalled when scientists pointed out that such a law might endanger research on stem cells. But Congress wanted something done, so the issue was handed over to the FDA. The agency effectively banned the procedure by insisting that cloning projects go through the same application process as experimental new drugs, knowing it couldn't survive this gauntlet. Meanwhile, laws were passed in some states to make cloning a felony. Anticloning groups sprang up in Britain and France. Italy passed a law that forbade anybody from cloning anything. The United Nations declared that cloning people is "contrary to human dignity." Late last year, Japan banned all human cloning research. Not all nations followed suit, however: Singapore, India, Russia, and Brazil are among those that have not outlawed human-cloning research. A few people came forward to argue that, just maybe, the world was overreacting. Rabbi Michael J. Broyde of Emory University in Atlanta wrote in the journal Jewish Law that "when no other method is available, it would appear that Jewish law accepts that having children through cloning is perhaps a mitzvah in a number of circumstances." Isaiah Berlin, Francis Crick, Richard Dawkins, Antony Flew, Herbert Hauptman, Simone Veil, Kurt Vonnegut, Edward O. Wilson, and other luminaries signed a "Declaration in Defense of Cloning and the Integrity of Scientific Research." But leaders weren't listening. "I would write to politicians about it, and they responded as if anybody who wanted to clone was a Nazi," recalls Mark Eibert, an attorney based in San Mateo, California, who represents infertile couples and who advocates cloning. The uproar was so intense that, as most IVF experts will tell you, it's the societal anticloning zeitgeist and not the FDA that stops them from openly trying to clone people. "It would be seen as bad behavior to be into it," Willadsen says with barely disguised contempt. Perhaps mindful of this perception, the American Society of Reproductive Medicine recently published a hedge-the-bets report from its ethics committee, declaring that cloning might be justifiable in some cases, that its morality is an open question, but that current safety concerns dictate that IVF doctors shouldn't do it. Amid all the condemnation, ethicists have been hard-pressed to explain exactly why cloning is a bad thing. They worry about how a clone might be treated by society; they use words like "insult to human dignity" that seem like really just another way of saying, "ewwww." University of Chicago ethicist Leon Kass uses the term "yuck factor" to describe this gut-level response. Kass, who opposes human cloning, says we should listen to our inner voice and avoid "transforming procreation into manufacture." Critics also point to animal cloning's spotty safety record. Miscarriages and neonatal deaths still plague the science. Bovine clones often show abnormal placental and heart-lung development, leading to miscarriages or death soon after birth. Most cloners believe these problems result from the incomplete reprogramming of the DNA's "mammalian imprinting," the instructions that tell stem cells how to become, say, liver or skin cells. How could we possibly attempt such a thing with human embryos? Of course, we've heard all this before. In 1978, after British scientists Robert Edwards and Patrick Steptoe produced Louise Brown, the world's first "test-tube baby," plenty of people were horrified. Illinois enacted legislation that granted IVF doctors custody of the embryos they created, potentially trapping them into being charged with child abuse if something went wrong with the procedure. The Catholic Church was (and remains) an especially vociferous opponent of in-vitro fertilization. In the early days of IVF, the success rate was only about 5 percent per treatment round. There were miscarriages and "wasted" embryos. Experimentation was done on humans first, not lab primates. But still the customers came, and despite the early condemnation, despite the risks, IVF was rapidly accepted. Today, thousands of women every year are having babies thanks to IVF. The success rate at well-run clinics has risen to between 20 and 30 percent per cycle - 50 percent after repeated tries. Despite this great progress, there are still miscarriages, just like natural reproduction, and unneeded viable embryos are still discarded, two common criticisms voiced by opponents of cloning. But the downside is accepted as justified to help people have babies. Cloning may go the same route. "When some new technique comes out, people always panic," says John Zhang, a New York-based IVF researcher and clinician. "Then everybody loves it ... Cloning will be the same thing. Eventually people will accept it, if it proves successful and safe." Animal cloning is so easy now that a layperson can perform some of the more basic operations, as I learn during a visit to the Infigen nuclear transfer lab outside Madison, Wisconsin, arguably the leading animal-cloning facility in the country. In a dimly lit, spartan room humming with an incubator, Jeff Betthauser, a nuclear transfer specialist, seats me in front of a micromanipulator. The device looks like a very sophisticated microscope, with two small arms projecting into the stage of the scope from the left and right. These slender arms hold glass pipettes that manipulate cells; the arms are controlled by a joystick and delicate hydraulic pistons. Betthauser shows me the ropes. First, wrangling an oocyte that sits in a petri dish, he maneuvers it into the grip of a pipette. Then he punctures the oocyte with the other pipette and sucks out its nucleus. He changes pipettes, sucks up some somatic cells, and forces one into the egg. He bats the egg away and sets up another. I try it, and Betthauser praises my work. If you've been doing it awhile, you can "NT" 50 to 100 eggs in four hours. Cloning involves more than the manual skill of nuclear transfer, but this is the crux of the process - just as it would be in human cloning - and it's not very different from the way some IVF procedures work today. But, IVF clinicians live in a very different world than would-be human cloners like the Creator. They are cowboys on a medical frontier, able to push their science as far as they want, to respond to the demand for increasingly sophisticated reproductive tools - almost everything but cloning - because IVF is largely unregulated. Clinicians are free to conduct their own experiments and invent new techniques, which can seem every bit as strange as cloning. "Some things have occurred in our field because a guy says I am going to do it, and I have a center to do it, and I'll just do it, dammit, and I do not need your permission," Mark Sauer says. Sauer tells me he's just that kind of man - a person "who has always questioned authority. I am not one to simply accept the status quo." In the past, Sauer has pushed the envelope by causing perimenopausal women to become pregnant. Now he's helping "HIV discordant" couples - with one HIV-positive partner - have babies, despite the possibility of transferring the disease to the newborn, a risk Sauer says is small. So it's not surprising that Sauer, or someone like him, might also challenge the cloning taboo. Sauer tests IVF's boundaries not because he's addicted to notoriety but because he hates telling women they're never going to have children. "That has to be on a par with telling somebody they have cancer, or a terminal illness, or that somebody died. It is a very sobering message. I see people cry as if I told them their mother just died. Maybe you hoped for it your entire life, and then you realize it is not going to happen for you. You get whole decades of emotion." IVF cowboys respond to that emotion. Cappy Rothman, a fertility doctor at UCLA, has made a specialty of removing sperm from dead men to help them father children. Severino Antinori, a prominent IVF doctor in Rome, has caused a 63-year-old woman to become pregnant, grown human sperm in rats, and once agreed to try and help an unnamed Catholic priest have a baby by taking his unejaculated sperm - thereby leaving the clergyman's celibacy intact - and fertilizing the egg of a surrogate. Jacques Cohen of New Jersey's St. Barnabas Medical Center - an IVF star who worked with Steptoe and Edwards and now works with Willadsen - has pioneered a process called cytoplasmic transfer. This technique closely resembles the micromanipulation steps used in cloning: Cohen transfers the cytoplasms (the cellular goo outside the nuclei) from one woman's healthy eggs into another woman's defective eggs. The theory is that the defective mitochondria - the engines in the cytoplasm that power a cell - might be replaced by mitochondria that are humming along, so a woman could still produce a baby who shares her genes. Each mitochondrion has its own DNA, so strictly speaking, a baby resulting from this procedure would have two genetic mothers. Although babies have been born following successful cytoplasmic transfers, nobody is quite sure whether the births occurred because of the procedure or just luck. Jamie Grifo, a clinician and researcher at New York University School of Medicine, and his partner, John Zhang, approached the problem of balky eggs another way. They simply transferred the nuclei from the eggs' worn-out cytoplasms into the cytoplasms of healthy eggs. In other words, they performed nuclear transfer. It wasn't cloning, because they were trying to fertilize the reconstructed eggs with sperm, but it was about as close to cloning as you can get. Nobody who works in IVF - even people like Grifo and Aussie animal-cloner Trounson, who oppose human cloning - has any doubts about where this is leading. Neither does the federal government. After Grifo's work was announced in October 1998, he got a call from the assistant surgeon general of the United States and, he says bitterly, "my research got shut down." Grifo's clinic was paying for the research, but he says the controversy made NYU uneasy, so he voluntarily backed off. Two weeks after that call, the FDA sent out one of its "Dear Colleague" letters, reminding IVF players where the lines were drawn: "The purpose of this letter is to confirm to institutional review boards that the FDA has jurisdiction over clinical research using cloning technology to create a human being." This despite the fact that IVF is not subject to such restrictions. But Jan Tesarik, a researcher at the Laboratoire d'Eylau in Paris, followed up on Grifo's work, and announced last spring that his team had developed a new way to fuse one woman's egg with an enucleated egg taken from another donor. The trick was using chemicals to fuse the two eggs, and avoiding the more common technique of electrofusion that can activate eggs prematurely. Tesarik & Co. published a paper last May in the journal Human Reproduction that connects the dots: "For eventual future use in human cloning," they wrote, the technique would "ensure prolonged exposure of transferred nuclei to metaphase promoting factor, which appears to be required for optimal nuclear reprogramming." The same equipment used to clone animals at Infigen is used in IVF techniques, most commonly in intracytoplasmic sperm injection. ICSI was developed for sluggish sperm that don't have the gumption to penetrate the egg's exterior, the zona pellucida. IVF technicians give these sperm a boost by injecting them directly into the egg's cytoplasm. If there are no sperm in a man's ejaculate, a needle can be inserted directly into the testes. The spermatozoa, or even round immature spermatids, can then be injected into the eggs. Sauer says that any lab doing ICSI probably has the skills and equipment necessary to clone a human. Most IVF labs around the world perform ICSI, including the one the Creator says he will use. For his part, Sauer would like to clone, too. Not adults, necessarily, but embryos. If Sauer could clone embryos from an IVF cycle and store them in case a pregnancy fails, or in case a woman wants a second child later on, much of the pain and expense of another round of IVF could be avoided. "It would be easy to clone identical embryos. That could be done right now in almost any IVF lab, to make three or four copies." Cloning an adult would be a little tougher, he says, because of the mammalian imprinting issue, but the idea is the same. "If you had a good cell biologist, you could do this with two people. You could do it in a small closet. It would not cost much if fixed expenses were covered, like the doctor's time and the lab equipment." Sauer puts the price at around $50,000, maybe $60,000 - not much more than what many patients pay for several IVF cycles. The cloning underground knows all this. "I cannot go through the week without people asking for it," Sauer says. "They say, 'Can't you just do it for me? I'll be your guinea pig. You can experiment with me.'" It's quite likely that some of the people begging Sauer to clone them heard about his work from Randolfe "Randy" Wicker. From inside Uplift, his overstuffed antique-lighting store in Manhattan's West Village, Wicker serves as the public face of the Human Cloning Foundation. He's an enabler, a one-stop resource for science news and rumors, and for people who want to be cloned and those who say they'll do it. Wicker is a 63-year-old man with thinning gray hair and mischievous, if slightly sad, blue eyes. He is a longtime gay rights activist whose experiences have made him fearless. He will say and do anything to advance the cause of human cloning - even though his colleague Brad Hennenfent, an Atlanta MD who founded the HCF, worries that exposure will damage Wicker's reputation. (Hennenfent did not respond to repeated requests for an interview.) Wicker is always good for a quote, always willing to be outspoken, a trait that titillates the media and delights the cloning wannabes who contact the HCF homepage. There, no request goes unanswered, no story receives an unsympathetic response. To a fur fetishist who wants to create a Russ Meyeresque "fox-woman" mate - a chimera combining the features of a fox with those of a human female - Wicker says he understands, then lets the lonely fellow down easy. To the guy whose email message reads, "I need a new penis cloned!! (seriously)!!! Help!!," Wicker empathizes about the important psychological bond between a man and his sex organ. Wicker understands, because he desperately wants to be cloned himself. "I have $350,000, and I would clone once, maybe even two or three times, and put them up for adoption to heterosexual parents," he tells me. "I would choose parents who had gay relatives, so the family would be comfortable whether my clone was gay or not. I would be the special uncle in the family, provide support for education. It would be an incredible experience, watching your later-born twin." The possibilities don't stop there. "What if they had cloned Beethoven at different times so you have clones that are 40, 30, 10, 5, 2 years old!" Wicker says. "You would have a second tier of relationships that never existed before. I call it a clan. 'Oh my God! One of our Beethoven brothers is an orphan, because his parents were killed in a car crash! Well, I will raise him.' Of course, there will be an immediate understanding, a connection between them. It will be a wonderful, special adoption." Wicker's bizarre vision reminds me of Kurt Vonnegut's Slapstick. The novel's main character wins the presidency by running on the slogan "Lonesome No More!" He proposes to banish loneliness by giving everybody a host of designated relatives. While it may sound crazy, Wicker's quest is driven partly by what many of us crave - not weird canine-human hybrids or new sex organs, but family. You see this desire played out repeatedly as you meet people in Wicker's extended network. Rebecca (not her real name) has tried for years to have kids. She is 35, lives in California, and has access to state-of-the-art infertility treatment. But in a letter to the Advisory Committee on Human Cloning, a study panel established by the state's anti-human cloning law, she describes a "nightmare odyssey through these various infertility treatments... Suffice to say I have been through hell and back. After 10 artificial-insemination attempts and four IVF cycles, we have exhausted our financial resources and nearly ruined our marital relationship." "Adoption was never an option," Rebecca tells me in a subsequent phone conversation. "We took vows to raise a family and to raise our own children. I know people will criticize that. They will say you can adopt a child and love it as your own, but something tells me that is not natural." Rebecca has made contact with a man who says he might try to help her clone. She is, by the way, a born-again Christian, and she sees nothing in the Bible that tells her cloning is wrong. Simon (also a pseudonym) is an ultra-Orthodox Jew living in an Hasidic enclave in upstate New York. "Women talk about pregnancy all the time," he says over the phone. "If you are not able to make it happen, it gets talked about. There is absolutely pressure." Simon is 29, and his friends already have several children. But he can't produce sperm, and he feels pitied. I ask about using donated sperm, but he says this would be like sending his wife out to commit adultery. "It would be against my religion. It would not be a kosher child." So Simon wants medical science to place his clone inside his wife. He wants it so badly he would spend "more money than I would ever have in my life. I would go beg." He came to Wicker seeking a doctor who will help him out. Marion Vuchetich is a 77-year-old retired high school biology teacher living in Georgia. She is still distraught over the loss of her son, Matthew, who died in a 1998 tree-trimming accident. Marion says Matthew was a bright, handsome 37-year-old, fascinated by science. He was engaged to be married. It nags Marion to think what the world lost when he was killed. Something special was in that DNA. So when Vuchetich contacted LifeLink - an organ-donation program in the Atlanta area - she asked if a few square inches of Matthew's skin could be preserved. "I thought, well, something in the future will be done, and I have an open mind," she says. Messages like these pour into Wicker's email box every day. There's one from a 42-year-old woman who has a child, but has been unable to conceive another, even after attempting IVF. She wants to know if "it would be against moral codes to try to clone my daughter." There's one from the mother of a "loving, articulate, sensitive, kind, talented, creative" 18-year-old named Jesse who died last year. The overall sense you get is that more and more people are starting to see cloning not as something they might have, but must have. "I am 36 years old," one of Wicker's female correspondents writes me. "When I was 14, I had a brain tumor that made having a child impossible. I have heard all the reasons for adopting and fostering, but why should I be exempt from the right to a child with my genes?" Infigen's headquarters sits at the intersection of Genetic Way and Infinity Drive, on a patch of land next to a cornfield about 10 minutes north of Madison. If human cloning ever becomes an aboveground enterprise, Infigen will inevitably have a say in the matter, because the company owns a US patent for activating egg division by mimicking what happens when an egg is penetrated by a sperm. There are many ways to accomplish this - electricity and chemical stimulants, for example. But, Infigen's Michael Bishop says, "It doesn't matter if you use a ball-peen hammer." Infigen owns the patent on the crucial step, and it will sue. Of course, as Bishop admits, there's not much the company could do about human-cloning researchers who operate in secret or in other countries. Infigen wants to become the world's leading "pharmer," making money off procedures such as cloning genetically altered pigs to produce organs for human transplantation and harvesting human proteins from cow's milk. For its business model to work, animal cloning's success rate must improve. There is still a "5 percent efficiency barrier" in adult somatic cell nuclear transfer. This means that, out of 100 nuclear transfer oocytes, only five live births will occur - the same rate as early IVF. That's not good enough for profitability, so Infigen constantly tweaks the cell-fusion and egg-activation process and tries variations, like using fetal somatic cells instead of adult cells. The goal is to erase the mammalian imprinting on the somatic cell's DNA. Infigen has done so well that its efficiency has climbed to 30 percent - the same standard as human IVF. Now the company has started using DNA microarrays to see exactly what the genes of a healthy embryo look like, a strategy Bishop says will someday boost efficiency even further. This could make cloning - of cows, pigs, or people - even more efficient than natural reproduction. Infigen's advances inevitably force its technicians and scientists - several of whom meet with me in an Infigen conference room during my visit - to ponder the possibility of human cloning. They'll talk about it only grudgingly. Officially, the company has no interest in human cloning and won't pursue it, but its scientists understand that their work could help overcome the most cogent objection to the procedure - its poor safety record. Bishop asks the researchers how they would react if "I came in here tomorrow and said, 'Take these human stem cells and start making embryos out of them.'" Jeff Betthauser, the nuclear transfer specialist, pipes right up: "I could not do it." "To me it is an emotional issue," says Erik Forsberg, director of cell biology, who couldn't do it either. But as we keep talking, it's obvious that the process of researching animal cloning has made the human version seem less bizarre to these men. They've come to see animal cells and human cells as tools - amazing, even awe-inspiring tools, but tools all the same. "I do acknowledge God and church and things, and it took me awhile to even be comfortable with animal cloning when we first started out," Betthauser says. But he got used to it. "Then, when we talked about transgenics" - adding new genes to cows and pigs to produce designer clones - "I said, 'Hey, that's a little different!' But after learning more about it, I was not too afraid of it." He got used to that, too. Objections to human cloning are fading in just this way. Bishop says he would never do it, but his fear of the idea has vanished. "This is a subject I have faced since day one, and I am not as shy as I used to be in terms of talking about it," he says. "The party line was: 'We do not do human cloning. We are interested in agriculture.' Now that has kind of gone away. Let's face facts. A cell is a cell. It doesn't matter where it comes from." So Bishop no longer gets worked up over the prospect of someone else cloning humans. At first, I'm puzzled about why this is so, but after our discussion, a few Infigen employees take me out to a rolling meadow to meet some clones. When I get there, I see cows. I see cows lying down and cows standing up. I see cows that think they are pets and sprint up to me and step on my foot - and I realize that cloned cows are as heavy as regular cows. But I also realize, as I think the Infigen folks do, that if there is such a thing as a cow soul, each one of these cows has a soul of its own. Cloning does not produce perfect copies. Even on the surface, these cloned cows - about 20 of them, all cloned from the same parent - are not exactly alike. "We have several you cannot tell apart," Bishop says, "and then others that did not get the star on the forehead, or the white moved down the leg farther, this and that. There are slight variations. There are lots of little things that control the cells that determine pigment. The biggest is the surrogate mother's uterus. What is she experiencing at the time? How is the fetus positioned when the melanocytes (pigment cells) migrate into place? Maybe she was having a bad-hair day." The uterine environment can even shape behavior, Bishop explains. Hormone surges can create differences in the fetal brain. The wiring of the clone's brain may be significantly different from that of the original animal, depending on what the surrogate heard or tasted or ate, or exactly where in the uterus the clone gestated. And of course, there is the egg's mitochondria and its DNA. Nobody is quite sure precisely what effect this DNA has on the nuclear DNA, what directions it gives or takes, even what diseases it may influence. "Maybe the mitochondrial expression of certain genes triggers the expression of nuclear genes in a very synchronous way," Bishop suggests. "How that happens, we really do not understand. In frogs, there is a strong mitochondrial effect on the nucleus. There is cross-talking going on." These two biological factors also interact with environmental factors, and are even affected by the passage of time. A clone is not born at the same time as the parent it's cloned from. They each see and hear and taste different things. None of this should surprise us. Identical human twins, which are much closer to duplicates than any clone would be - same egg, same placenta, same womb, same gestation time frame, same parents - are not exact copies. Just ask one. That's how it will be with clones, many experts believe. So if a woman like Simon's wife were to carry one of her own eggs filled with a nucleus from his cells, their child would, in fact, be a combination of them both, not just a carbon copy of the father. Yes, the child would be male, and, yes, he would look an awful lot like Dad. The boy and his father might have some other striking similarities, too. And it is true that the mitochondrial DNA from the mother would be only a small percentage of the clone's genome. But it would be there, and the clone would be born of a different mother than Simon was, and raised in a different household at a different time. Bottom line: There is no such thing as making exact copies of people. This is why Steen Willadsen says that if you want to create people who are identical, cloning might actually be a bad way to do it. "It is retrograde to clone," he says, a little tongue-in-cheek. "There are other ways of making people identical. We can put them through the same schools and subject them to eight hours of TV every day. That works a lot better. Why do you think Americans are buying SUVs?" From Montreal, it takes about an hour by highway and country roads to reach a huge white barn painted with the word "UFOLand." This is a home base for the Raelians - Clonaid's founders, and religious believers who teach that advanced extraterrestrial beings called Elohim landed in France in 1973 to meet aspiring race-car driver Claude Vorilhon. They changed Vorilhon's name to Rael, told him that humans are clones of the Elohim, and revealed that someday he will lead mankind into a blissful techno-utopian future. Rael was to be the last prophet, the end of the line that includes Moses, Jesus, Mohammed, and Buddha. I'm here on this gloomy, drizzly day, because the Raelians have announced that they have secured funding to clone the deceased 10-month-old of an American couple - making them, aside from Graeme Sloan's co-op, the only group or individual to publicly announce a human-cloning project. The Raelians are bouncing with optimism. Raelian Mark Proulx gives me a quick tour of UFOLand, a series of rooms with strange exhibits: There's a replica of the silver saucer Rael saw in 1973, an enormous amino-acid totem pole that models DNA, and a room dominated by a photograph of Rael that hangs over a short set of steps leading to a kind of stage. A silver cup sits under Rael's picture. It's a trophy: Third place in the 1997 Dodge Dealers of Connecticut Grand Prix. I'm taken into Rael's quarters, which look like the bedroom of a particularly neat 15-year-old with permissive parents. A series of photographs featuring a nude young woman - Rael's wife - hangs on the walls. At his desk are two computers, one equipped with a steering wheel for virtual reality racing. Rael is dressed in his standard uniform: billowy white trousers and a broad-shouldered white vest over a white tunic. His long hair is tied into a topknot on his balding head. For a prophet, Rael is a pretty funny guy. No doom here, which is not surprising, since Raelianism is characterized by a free-love philosophy that has made Rael a sort of New Age Hugh Hefner. He surrounds himself with beautiful women, who form a kind of fashionista offensive line behind which Rael enters rooms. Rael is fond of Mao-esque pronouncements like "the Internet is a religious process." Cloning for the Raelians is a religious process, too. "It will give us eternity, which was the genetics of the Bible," he tells me, citing the long-lived Jewish patriarchs of Genesis. Very soon, we will live "700 or 800 years; then, through cloning, eternal life. Cloning is a primitive step. We only know how to make a baby. Step two is not here yet. It is an accelerated growth process. Take one cell of your body, put it in a machine, and you have a young adult, which will make obsolete the need to have a surrogate mother." He believe clones will someday pop out of machines fully formed as 17-year-olds. Why 17? "That is when human beings are at their best. These are like a blank tape. Then you take the personality from your body and unload it onto this blank tape." We will need to repeat this process every 700 years or so, because even these cloned bodies will wear out. Rael is looking forward to cloning because, at 54, he's not the man he used to be. Being 54 isn't fair. He has a nice sex life, thank you very much, and he races cars, but he's losing his hair. "I am not happy with things as they are," he says, "with people staying younger than me." The Raelian project is an effort to hurry things along, and Rael is confident his people have what it takes. Brigitte Boisselier, Clonaid's director, is a chemist who claims to have been fired from French chemical giant Air Liquide and to have had her youngest daughter removed from her custody by French courts in retaliation for her views on cloning. She now works as a visiting professor at tiny Hamilton College in Clinton, New York, an easy 190-mile drive from UFOland. And, thanks to Rael's covey of fertile young women - more than 50, including Boisselier's 22-year-old daughter Marina - Clonaid will have all the eggs and surrogates it needs. "I bring the surrogate mothers and support them spiritually, religiously, according to the new rules of humans," Rael says. For weeks after my meeting with Rael, he and Boisselier attempt to sell their plan to anybody who will listen: radio shows, newspaper reporters, potential customers. Most of the coverage emphasizes the wacky factor, but they're quite serious. They even show up in San Francisco to sell cloning as a parenting option for gays and lesbians. Still, serious intentions do not mean serious results. The more they say, the shakier it all sounds. For starters, this is not the first time the Raelians have launched a cloning program. Soon after Dolly, they started a cloning effort - also called Clonaid - forming a Bahamas-based corporation that was supposed to clone people in Bahamian labs for a fee of $200,000. But there never were any Bahamian labs. Today, Boisselier tells me that plan was only "a concept." Persistent rumors within the cloning underground, however, suggest that this wasn't what the Raelians were telling clients. According to Graeme Sloan, some of his people contacted Clonaid and were asked for big money up front. Now, when I press Boisselier for details, she still sounds vague. She estimates the first clone in the current project will cost about $500,000. She says she has hired four scientific staffers: two biologists, one geneticist, one MD. The MD is an IVF specialist. A lab is being equipped. The lab, she says, is not in Canada or the US - but she won't say where it is. She tells me work got under way in October, and that the Raelians plan to throw open the doors of their lab to almost 200 people who are ready to pay for cloning services. (These customers will pay $200,000, quite a markup from Sauer's estimate of $50,000 to $60,000.) I ask to see the lab, but Boisselier says she'll take me there only if I pay a year's worth of her salary, an offer she knows I won't accept. Perhaps she's money conscious because the costs are going up. During the Raelians' October news conference in San Francisco, attended by Rael and his all-women advance team, the prophet says the price tag has doubled. Now it is $1 million. Maybe $2 million. When I arrange for a woman to contact Boisselier by email, posing as a prospective client, there are more discrepancies. Apparently, Boisselier lied when she told me the lab was not in Canada or the US. It is "in the US," she writes to my friend. "It won't be in California, since there is a California law against cloning there. But there are many states without regulations." That's not quite true, as long as the FDA's ruling stands. After reading a press account speculating that the lab is in Nevada - home of Clonaid's PR director, who lives in Las Vegas - I contact the office of Nevada's senior US Senator Harry Reid, whose staffers were already on the case. They say they've tried but have been unable to track down any such lab. So I contact Boisselier again. The lab is almost ready, she tells me: "We anticipate to start the work on human cells mid-January." When the customer asks to see the lab, Boisselier refuses. "We don't want to show [it] yet," she writes. "I could only show you a video, but we don't want to be traced yet. We don't fear the government, actually - they can trace us very easily - but we don't want journalists or anticloning gangs to visit us." Boisselier told me there are four staff members; she tells the customer there are three. One, she says, is a Harvard Medical School graduate - not nameable, of course. When I voice doubts that there is a lab, or a couple ready to buy a clone, Boisselier says, "I have been honest from the start, but you should be aware that we are moving fast. If you publish your article in February, we may already be about to send a press release on the first embryo. You cannot accuse me of hiding things.... I am the leader of a project, a project unanimously despised, and it takes a lot of my energy to make sure that everything is done properly on the scientific side, that the humans involved are protected from the hate of their neighbors and colleagues." Later, when the customer tells Boisselier she might be willing to go public in support of the cloning cause, Boisselier jumps at the offer, noting that "the family that is sponsoring our work today has also agreed to go public when it is time.... They will when we succeed and bring the nice baby in front of the camera." She might be able to arrange interviews, she says, with NHK of Japan, the BBC, or ABC's 20/20. Then, a few hours later, Boisselier drops a bomb in another email to the customer: The first-string couple may be willing to step aside. Boisselier says the original child's cells were frozen, which isn't ideal. "If we proceed with frozen cells," she writes, "and have no results, we may question the quality of the cells. However, if we proceed directly with living unfrozen cells, we will control that parameter.... We have several candidates who would be willing to be the first ones to be cloned but none would agree on being public." Would the customer, with her fresh cells, like to be first? This is a strange statement, because cloners use "frozen" cells all the time. When needed, these samples are thawed and cultivated to grow new generations of cells whose quality can be verified before being used for nuclear transfer. Whether the cell line used for NT is derived from "fresh" or "frozen" samples, it should work fine (with only marginal fall-off from cells derived from a frozen sample) because, in the end, all the cells used are "fresh." These obvious discrepancies aside, even the Raelian method of cloning seems dubious. Boisselier tells the customer that Clonaid will not use either of the two types of cells that appear to be best-suited for cloning, fibroblasts and cumulus cells. She says Clonaid could take a cell from a blood sample, put it into a donor egg, and go from there. Though at least one animal has been cloned from a leukocyte (a white blood cell), blood is not considered a good source of somatic cells for cloning. Clone-buyer beware. There is a fundamental difference in tone between the IVF and animal-cloning scientists and the human-cloning underground, and it takes me a while to pin down what, exactly, that difference is. It hits me after I visit Rael: The underground is breathless because it is looking at the present and never all the way to the future. But the scientists are blasť about the present, perhaps because the future looks much stranger. "I'm not surprised somebody wants to clone human beings," John Zhang says. "I've been pretty sure from the beginning that somebody was going to try it and be successful." The tribal consciousness of animal cloners thinks human cloning has already been done, but quietly. This way, there is no government or social wrath, no reputations ruined, no patents publicly infringed. "Unregulated IVF clinics with millions of dollars and a patient wanting a child?" Michael Bishop says. "I will let your imagination run." Even if humans have not been cloned on purpose, they may have been cloned by accident. For example, cumulus cells often hang around gametes - eggs and sperm. One was attached to the egg I worked on at Infigen. "You know," the University of Wisconsin's Neal First tells me, "there is an interesting aspect to ICSI. When you get that spermatid out of the testes, they purposely fracture the tails of the spermatids so that when you pick up a cell you do not know much about it. It's a round cell. It may or may not be a round spermatid. Some people connected with ICSI think that the technicians make mistakes and do not always get the spermatid, but may get a somatic cell in the vicinity. It's probable transfers have been made - and the human oocyte treats everything that enters it like a sperm cell." As he tells this, I keep wanting him to be excited or horrified - something - but when scientists make such observations, there's an old-news feeling, even among those who oppose human cloning. "It would not bother me to have another set of twins in the world," Alan Trounson says. "Identical twins are clones, and we are quite happy to have them in our community." But the underground - and the rest of us, too - is still fascinated by the rumor mill. Something is happening. Or about to happen. Or has happened. Nobody is quite sure. The mill grinds. One bioethicist tells me he knows of maybe half a dozen labs around the world where he thinks human-cloning experiments could be going on. He won't reveal their names for fear of a lawsuit. Graeme Sloan says he's heard of one in Scandinavia. And what about Korea? Or Israel? Meanwhile, the Creator is fretting because he thinks he's losing a race against unseen others. Months after our meeting, his collaboration with the Client appears to be dying. "I have asked him to put up some money but he is hesitating," the Creator says in an email. "I have a sinking feeling that if I do not get started soon, I am going to lose IT!!!" Still, he's not going to give up. "You were saying you knew of a couple who wanted to clone their dead son. Do you think they might be willing to go to [Asia]?" IVF cowboys and animal cloners display none of this anxiety. That's because they are looking ahead. They know the point of Dolly was not that you could make a clone of an adult mammal - the place where most of us have gotten stuck. The point was that Dolly proved our cells really are Play-Doh. Our genes are plastic. They can be shaped and molded. Organisms can be designed. "It opens up new possibilities with medical overtones," Willadsen says. "Primarily stem cell research. That's the big area of interest. Reproductive cloning is a very distant second." Infigen and others are trying to isolate the specific enzymes in the egg cytoplasm that erase the DNA program. If they succeed, cells could be made totipotent, or embryonic, without using an egg. Stem cells could be manufactured, instead of harvested. And new tissues could be generated by directing these stem cells. Artificial human chromosomes were created four years ago, and "artificial sperm and eggs are pretty close now," Trounson says. Human beings may someday be designed from scratch, and microarray technology will end the guesswork. Ultimately, we may not even need mothers. Work on an artificial womb is progressing nicely. So it doesn't take much of a leap to imagine a time when a mother and father, one of whom carries a gene that makes cancer more likely, or causes a catastrophic disorder in children like Fanconi's anemia, enter the IVF clinic to design a baby who will not get these diseases. And maybe the child will be a little taller and smarter, too. This sort of thing is a ways off, but it will happen. It's easy to see why scientists looking into that future have a tough time getting worked up about the race to produce a copy that isn't really a copy.