Meet the first human clone, in this WIRED scenario.

Also: Go Forth and Multiply - Richard G. Seed on why cloning is God's work.

__ She knew she'd have to explain it, __ probably even apologize for it, sooner or later, but Dr. Amanda Koteas didn't think she'd be doing it now. Nevertheless, after weeks of rumors and stolen memos and lab reports turning up in the tabloid press and on TV, Koteas, head of the University of Pennsylvania's Department of Molecular and Cellular Engineering and the school's Institute for Human Gene Therapy, decided to tell the full story. At a hastily pulled-together press conference last Friday, she announced to the world that not only is human cloning possible, but that she and her team had already done it - two years earlier, using an updated version of the techniques scientists at the Roslin Institute used to create the sheep Dolly, the first mammal cloned from an adult cell, in 1997.

The result of Koteas and company's bold experiment was a healthy 8-pound girl named Katy, born in secret to Virginia and Christopher Hytner at the institute on December 5, 1999.

Why did Koteas wait so long to go public with the story? During our interview, it is clear that she remains moved by the child's birth, but ambivalent about discussing the cloning. "This was a medical procedure with a name and a child's face," she says. "We were hoping to keep the circumstances of Katy's birth out of the public eye for a few more years at least. She's a normal kid and deserves a normal childhood."

It's unlikely anything about Katy Hytner's life is going to be normal for years to come. Not only has the press descended on Pacifica, a coastal community 20 minutes south of San Francisco, but so have religious groups, film and book agents, and conspiracy buffs. While Pacifica is used to tourists, the current mix of curiosity-seekers is not sitting well with local residents. Says Thomas Winkler, owner of the Good Morning America coffee shop, "It's like there was an explosion at the idiot factory and all the debris landed here." Punching receipts into his cash register, Winkler reflects for a moment before adding, "They should all just leave that little girl alone."

The Hytners are not the only ones overwhelmed by the publicity surrounding this story. Koteas and her team are still trying to absorb the enormity of public reaction. "It's much more surreal than we ever imagined," she says. "Frightening, too."

Koteas and her colleagues have reason to be frightened. Several members of the cloning team have received death threats, while others, such as Adam Walken, whose studies into the genetics of aging encouraged the team that human cloning was possible, have been inundated with offers for movies and talk show appearances. In the corridors of the University of Pennsylvania, the words "Nobel Prize" and "jail time" are mentioned with equal frequency. School president James Osterberg has issued a terse press statement: "The university in no way condones the secret and unauthorized experiments conducted by doctors Amanda Koteas, Adam Walken, Eric Mortensen, Moriah Stoltz, and Albert Gomez. A full internal investigation is under way to determine whether any laws have been violated."

"We did the work using university facilities, so yes, technically, university funds were used for the work," admits Koteas. "And some of those funds were tied to government grants." The use of such funding, she acknowledges, defied the moratorium on human-cloning research encouraged by then-President Clinton in 1997. At her home in suburban Philadelphia, Koteas looks out the window. "We weren't conducting research for the sake of research. We were applying established scientific knowledge to a specific problem. I stand by that." She laughs anxiously. "If we win the Nobel Prize, I wonder if they'll let me keep mine in my cell?"

All this week, while the members of the Pennsylvania cloning team pondered their collective futures, Katy Hytner, an outwardly ordinary 2-year-old who had only last week been playing with Legos and Sesame Street dolls at the Oceanview Children's Center in Pacifica, was not yet aware of the controversy surrounding her birth.

__ Her "conception" began more than __ two years ago in the Prenatal Diagnosis Unit at the Institute for Human Gene Therapy. The university's cutting-edge combination of advanced computer analysis, genetic screening, and gene therapy had caused a stir in 1998, both as a scientific breakthrough and as a controversial moneymaking enterprise for the university (see " Buying the Future: Perfect Kids for Cold Cash," Wired 6.06, page 450).

Combining proprietary chemical and genetic tests for diseases and congenital abnormalities, all collated by the new "expert system" software developed at Carnegie Mellon University, the institute had developed a system that, according to its own publicity materials, "virtually guarantees not only a successful labor and delivery, but the healthy child every family dreams about."

Virginia and Christopher Hytner had talked about having children for years. "But we wanted to wait until the time was right," says Virginia, a part-time real estate agent. Her husband, a design engineer at Silicon Graphics in Mountain View, California, adds, "With our careers on track and our lives stable, the only things holding us back were health questions."

The Hytners, like a lot of the boomer generation, had waited until their late 30s to have children. While both were outwardly healthy, Virginia Hytner had some concerns about the health of any child she might bear. "Even though I don't have diabetes, my mother and an aunt do," she explains via phone. "I wanted to know about the possibility of passing that to my child. I also know that there are other problems that a child can have when coming from a diabetic background." Hearing of the University of Pennsylvania's successful screening program, the Hytners took their 1998 vacation in Philadelphia.

While much of the couple's concern centered on Virginia's genetic background, both prospective parents went through the screening process at the Prenatal Diagnosis Unit. This procedure is fairly simple for a man; only blood tests and sperm samples are required. Potential mothers, however, are injected with the hormone-based drug Metrodin to induce "superovulation." This bumper crop of eggs lets doctors collect samples for screening. Metrodin and related pharmaceuticals frequently bring on PMS-type cramps and other hormone-related discomforts.

Using the mother's eggs and the father's sperm, doctors fertilize several of the eggs in vitro. They then allow the fertilized eggs to grow until the eight-cell stage. Once the eggs have reached this phase, the doctors remove a cell from the egg and examine it using the university's proprietary tests, as well as a standard genetic-screening procedure known as nested PCR, a polymerase chain reaction that tags and amplifies DNA sequences so that doctors - or, in this case, a computer - can look for abnormalities.

For the Hytners, the tests indicated that the cell was clear of disease and congenital defects, and the couple chose to have the already-fertilized egg implanted in Virginia's uterus that day. Koteas, a native of San Francisco, performed that implantation herself, after meeting the Hytners during routine rounds at the Prenatal Diagnosis Unit. After an overnight stay and an exam the next morning, Virginia Hytner was released to rejoin her husband and plan the arrival of their first child.

But something went wrong.

It's not hard to believe the doctors and technicians at the Prenatal Diagnosis Unit when they say they still aren't sure what happened. Modern jet aircraft, handled by expert pilots and aided by the most advanced computers, still crash. In most of those cases, human error is the culprit. Was human error responsible for implanting a defective embryo in Virginia Hytner? We will probably never know. "There are nights I still lie awake wondering what went wrong," says Koteas. "Did a tech mislabel a cell culture? Or enter data into the new computer incorrectly? Did someone read a chart wrong? Was there something I did wrong?"

Virginia gave birth to a daughter on January 3, 1999. The child, which had seemed sluggish in the womb, was pronounced dead two weeks later of multiorgan failure.

The cause of death was a subtle one: neonatal lactic acidosis, a problem brought about by a defect in the mitochondria - microscopic organelles that control the metabolism of individual cells - in her mother's egg. A woman can be unaffected by the defective mitochondria in her cells, only to have them wreak havoc in her developing offspring.

The death of the Hytners' daughter devastated the couple. Even now, two years later and after the birth of a healthy child, Virginia can't completely describe how she felt: "Numb. I felt dead. After all the assurances of the doctors, I felt alone and betrayed." Koteas, who years before had lost a child to a rare chromosomal disease, trisomy 13, was also shattered by the baby's death. "We had done so well at the screening clinic, we started to believe the university's hype about us," she says. "We were perfect, and then we weren't, and a child was dead. It was awful."

Enter Adam Walken, Koteas's friend and colleague at the Institute for Human Gene Therapy. Walken was studying how cells change and break down as they age and was interested in finding a way to arrest or reverse this process. He had been studying in particular tiny sections of chromosomes known as telomeres - chemical buffers at each end of a chromosome that act like the bumpers on a car. They protect the genes inside from damage, but each time a cell divides, the telomere buffer often decreases in length. Eventually, the telomeres become so short that they can't protect the chromosomes, and the cell stops dividing and dies.

The question Walken - and other researchers - wanted to answer was, if you could restore or stop the erosion of a cell's telomeres, could you stop or reverse the aging process? One way to find out was through studying primate cloning. Could the older, telomere-eroded cells of an adult primate be restored to their pristine condition in an embryo during the cloning process? When the Oregon Regional Primate Research Center in Beaverton cloned a rhesus monkey, Walken received a National Science Foundation grant to work and study there.

While the results of his studies on aging are still inconclusive (researchers don't yet understand all the proteins that produce telomeres, nor the mechanisms that erode the buffers), Walken did learn about the basic science of primate cloning and was a member of the team that in late 1998 first cloned a chimpanzee (an animal so similar to humans that it shares 98 percent of its DNA with us) using the technique employed by the Roslin Institute. Walken has admitted that while he was working at the primate center, he was convinced that human cloning was possible but didn't think he would ever really know in his lifetime. "The climate was all wrong. Even to say the words was a heresy," he says. "When the Hytners' daughter died, something clicked in my brain. It wasn't something planned, but the logic was inescapable."

It was during a discussion over dinner that the subject of human cloning became serious for Koteas and Walken. Both had been experiencing crises of faith in their areas of expertise and were questioning the possibilities of technical fixes to problems such as aging and childbirth. "I told Amanda about depressions we experienced at the primate center during some of the cloning trials, but said that with concentrated effort, we were confident we had worked out a straightforward and reliable process to produce identical primates for study. She told me about her despair over the Hytners. Then, all of a sudden, we just sort of looked at each other." Depending on your point of view, either a conspiracy or a bold scientific experiment was conceived that night.

Despite the almost mystical power of the word cloning, the process happens constantly in nature and has become routine in labs around the world. Identical twins - normal children born every day - are clones. Amoebae clone themselves when they divide. For several years cancer and retrovirus researchers have been using groups of cloned mice to test drug treatments. Plants clone themselves when they send off shoots and buds. Many common fruits and vegetables such as apples, bananas, grapes, garlic, and potatoes have become grocery-store staples because of plant breeding and cloning. Cloning large animals in a lab, however - especially mammals - is more complex.

When the Roslin Institute conceived the clone Dolly in July 1996, seven months before the sheep was presented to the world, the big question researchers had to answer was whether an adult cell that had become specialized for one part of the body (in the case of Dolly's "mother," an udder cell) could be made to "forget" that it was specialized and return to a nonspecialized, embryonic state. Dr. Ian Wilmut and his associates at Roslin made a breakthrough using a process called demethylation. Simply, they kept normal nutrients from the cell and starved it in a salt solution until it became dormant and stopped dividing. This intervention allowed the Roslin team to fuse the sleeping cell's genetic material with another sheep egg from which the DNA had already been removed - a process known as nuclear transfer.

__ It took the Roslin Institute 277 tries __ to bring a single pregnancy to term. Still, it worked. After experimenting with rhesus monkeys for a year, the Oregon Regional Primate Research Center could achieve pregnancy every 50 attempts. When researchers there developed the chemical procedures to demethylate chimpanzee cells, they hit every 20 tries.

Once scientists have cracked the method of returning cells to their embryonic state, the rest of the cloning procedure is a relatively simple, mechanical process. After the DNA is inserted into an egg, the team gives it a microshock of electricity to fuse them together, and then another minuscule jolt - a sort of jump-start - to begin cell division. When the cells begin dividing, they are transferred to the mother's womb, just as in any ordinary fertility treatment.

In February 1999 Koteas and Walken determined that they had intact cell samples from the Hytners' dead child, and the two scientists approached the couple with the idea of, in Koteas's words, "giving them back their child - this time, the way she should have been when she was born." The Hytners were resistant at first, still in pain from their daughter's death. But when Walken explained his cloning experience at the primate center, and added the idea of implanting the baby's DNA in a donated egg from another woman - one who had borne healthy children - the couple started to come around. By the next afternoon, they had decided to try it. "They explained the procedure to us and said that they needed to start work as soon as possible to make sure our daughter's DNA was fresh and undamaged - that she was still, in a sense, 'alive' in her genes, but lost without a body," says Virginia Hytner. "Amanda and Adam made me and my husband believe that they could give our daughter back her body." At that point, the Hytners were sworn to secrecy.

The team of five doctors - Koteas, Walken, Mortensen, Stoltz, and Gomez - plus a handful of trusted graduate student assistants, set to work culturing the child's cells, chemically returning them to their embryonic state using samples of the advanced demethylating drugs Walken had procured from the primate center. According to Koteas, they also "obtained" frozen human eggs from the gene clinic, checking them again and again for the donor's history and any possible disease traits.

After fusing a dormant cell nucleus with a donor egg, the doctors jolted the egg with electricity to see whether it would divide. After only 10 tries, an egg started dividing normally, and Koteas implanted it in Virginia Hytner.

Over the next nine months occurred one of the most closely watched pregnancies on record. All five doctors on the cloning team made trips from Pennsylvania to California to monitor Virginia Hytner's progress. By then the Hytners were already calling the growing fetus Katy, a name they'd selected for their first child, who they later started to think of as Katy's lost twin. In fact, the university team had already coined the term serial twins to refer among themselves to the products of the cloning process.

In late November 1999 Virginia and Christopher Hytner took leaves of absence from work and, accompanied by Walken, flew to Philadelphia one more time. At 1 a.m. on December 5, Katy Hytner was delivered by Dr. Albert Gomez via cesarean section. The team was elated, and the Hytners were speechless. "Our daughter was returned to us," says Christopher Hytner. "It was the miracle we'd prayed for."

Since their work had not been approved by the university, the cloning team kept all their records confidential, hidden in a filing cabinet in Koteas's office. Still sworn to secrecy, the team went back to its work at the university and the Hytners returned to California with Katy. Team members still made regular monthly visits to Pacifica to check on mother and child, who both appeared healthy and safe. The reality of the unprecedented experiment remained protected from public scrutiny for almost two years.

Then, last November, a chain of events began that revealed the Hytners' secret. Alice DeWitt, a graduate student who had worked on the cloning team screening donor eggs, filed for divorce from her husband. During the stormy divorce proceedings, Matthew DeWitt found a set of notes - copies of papers Alice had given to Koteas - while he was removing his wife's belongings from their apartment. Matthew, himself a pediatrician, recognized the implications of the notes and offered them through his lawyer for sale to the highest bidder.

When news crews from the Hard Copy cable network began scouring preschools in Pacifica for Katy Hytner, the members of the University of Pennsylvania cloning team knew they had to make a public announcement. "We could see how things were going," says Koteas. "HCTV was turning Katy's birth into a Frankenstein story, portraying her as some frightening freak of science. As bad as things are now, we knew that if we didn't get hold of the story, the Hytners' lives would be ruined forever."

Koteas's press conference was beamed live around the world on CNN, MSNBC, HCTV, C-Span, and all 10 major broadcast networks. By then, the Hytner family had left Pacifica, and if anyone on the cloning team knows the family's whereabouts, they aren't saying.

Aside from the media, a number of other interested parties would like to find the Hytner family - among them Baby Gap, Pepsi, Benetton, and the Xerox Corporation, all waving lucrative endorsement contracts.

Now that human cloning has moved from science fiction films and research labs to the real world, what are we to make of it? No one seems to know yet. Dr. Richard G. Seed's operation, which moved from Chicago to San José, Costa Rica, in mid-1999 in response to pressure from the US government, has generated some interesting new approaches to large-scale cell culturing and fine DNA manipulation, but the facility has yet to bring any of its attempted pregnancies to term. Most of the European Union's member nations have passed strict laws preventing human-cloning work, though England and Germany remain holdouts. But it's generally known that Russia, Japan, and South Korea are setting up their own experimental cloning centers, perhaps in cooperation with Seed's lab.

One of the few unambiguous responses so far to Katy Hytner's birth has come from the Vatican, which released a statement urging people to recognize that clones have individual souls, even if they occupy identical bodies. Little else about what some are calling the Philadelphia Project is certain, even whether Katy is, in fact, a legitimate clone of her dead sibling.

Since she was produced in an egg that carried another woman's mitochondria, some scientists, including geneticists at MIT and Oxford University, question whether Katy can be truly considered a clone of the Hytners' first child. Perhaps the term serial twin is about to become common currency as Koteas and her colleagues try to calm a nervous public that, while admiring the motivations and technical skill of the cloning team, isn't sanguine about letting this genie out of the bottle.

"No one's about to start mass-producing copies of Adolf Hitler or rich people," assures Koteas. "This is one little girl - deeply loved by her ordinary mother and father. Trust me. There's nothing to worry about."

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