Double trouble

HOUSTON--Sen. Bill Frist, the Tennessee Republican, must have thought it was going to be easy-after all, even the president had voiced his support for a ban, however temporary, on human cloning.

It got complicated. Democrats countered Sen. Frist's bill (a simple, permanent ban) with a hollow alternative: a 10-year moratorium on implanting cloned embryos into a woman's womb. That would allow scientists to create-and then force them to destroy-human embryos. Sen. Frist's bill was denounced by Democrats, who called it a "know-nothing" approach that would stifle science; it was also denounced by prominent Republicans, who bought into the inflated medical claims of researchers that cloning could lead to cures for cancer, Alzheimer's, and Parkinson's. Sen. Strom Thurmond (R-S.C.), who has a daughter with diabetes, and Sen. Connie Mack (R-Fla.), who has been treated for melanoma, both expressed fear that an outright ban would impede medical progress. Sen. Mack noted there had been no hearings on the bill and said he worried about the legislation's possible "unintended effects."

Last week, Sen. Frist, a surgeon and the only medical doctor in the Senate, watched his bill bog down. Since he lacks the 60 votes needed to shut off a filibuster and move his measure forward, the cloning legislation is stuck in political limbo. That leaves many scientists to be governed only by their own consciences when it comes to cloning.

In much the same way, the science of cloning has proven more complicated than it first seemed. Even scientists in closely related fields find themselves asking questions about the implications of creating copies of people. "What is a clone?" asks Mike Miller, a plastic surgeon and researcher in the emerging field of tissue engineering. On Dr. Miller's desk at the M.D. Anderson Cancer Center in Houston are piles of articles from scientific and medical journals-the walls of his cramped office are lined with magazines, journals, and textbooks that don't provide that answer.

On a February morning, he's in between operations. He helped to rebuild a cancer patient's face; later he'll work on the chest cavity of another survivor. Dr. Miller leans forward, gesturing with his arms for emphasis: "If you take a cell from my mouth, and make a clone of me, is that clone still me? Is it mine? Can I do with it what I will?"

These ethical questions are much easier when dealing with animals. Dr. Miller and his fellow researchers have their own miracle sheep. The team is developing new ways to build tissues-bones and skin and cartilage and even fat cells-to replace tissues lost to damage or disease.

Some of the most promising work being done involves developing polymer molds for growing new bones. Mandibles, for example, are often lost to mouth cancers, and traditional bone reconstructions have proven unsatisfactory replacements. A mold for a new mandible was attached to a sheep's hip last year and tied to blood vessels there. New bone cells formed that new mandible, while in time the polymers dissolved. Within a few months, they had grown a properly shaped, fully functional replacement.

But Dr. Miller finds himself increasingly distracted these days by that other celebrity sheep: Dolly, known worldwide as the Scottish clone.

"This is going to be a battleground in coming years," he predicts. "We're seeing a powerful new technology being introduced into a society that no longer has the tools to decide between right and wrong." For every bioengineering challenge that she answers, he says, Dolly raises dozens of ethical questions.

What if it proves possible to create a clone that would grow only into a specific organ-a liver, say, or a leg? What if (as some experts predict) it becomes possible to make a clone without a specific organ-namely, the forebrain? Is that brainless clone a person? Or is it a living organ farm, devoid of consciousness and ethical baggage?

It's clear that science is rapidly outpacing society's ability to answer such questions, Dr. Miller says. With researchers left unfettered-there is only President Clinton's call for a voluntary ban on creating new copies of existing human beings-can they be trusted to make responsible decisions until legislation is ironed out?

"Doctors are fallen people, too," says Dr. Gene Rudd of the Christian Medical and Dental Society. Adds Dr. Miller, "Abortion is one indication of the value placed on human life by a significant portion of the medical community. I'd be hesitant to leave the issue of cloning in their hands alone."

An examination of the dubious history of cloning shows that researchers in the field are an eccentric bunch.

Hans Spemann, a Nobel Prize winner, spent the first years of the 20th century experimenting with salamander embryos. He found that if he used a baby's hair to split the embryos in two, he could often create twin lizards. But just as often, he created miniature monsters with two heads or odd numbers of limbs. It was he who first proposed "a fantastical experiment," cloning.

By the 1950s an American scientist, Thomas J. King, was ready to make the next big advance. He removed the nucleus from a frog's egg, then implanted into that egg the nucleus from a cell from a frog embryo. This was the first true clone; Mr. King was so delighted that he rhymed, "It was chubby and plump, a right jolly old tad/And we were to it both Mother and Dad."

Mr. King's announcement (if not his doggerel) caught the world's imagination. Suddenly human clones seemed to be just a few years away. But there was a catch. It only worked with the nucleus of an embryonic cell. For some reason that is still not understood, the older the donor cell, the less likely the frog would develop normally. This hurdle would not be overcome for more than 40 years, when Scottish researchers produced Dolly from a cell from a 6-year-old ewe.

In the 1980s, Danish researcher Steen Willadsen made the next big leap. Mr. Willadsen pioneered transgenics-mixing and matching genes from different species into one embryo. He made sheep-cow combinations, and he even barbecued one at a party in 1985. (Mr. Willadsen admitted that it didn't taste very good, but he said that was because the sheep part was too old.) Transgenics has led to the cloning of sheep and cows (from embryonic cells) that then produce proteins with a variety of medical uses. More importantly, Mr. Willadsen used cells that had already begun to specialize. The cells were still embryonic, but they were no longer "totipotent" or undefined cells.

Mr. Willadsen's work became the basis of Ian Wilmut's advances. In 1986, over drinks in a bar, Mr. Wilmut learned of Mr. Willadsen's achievements. At the time, the Scottish scientist was hitting a wall in his own research to engineer genetically cows that would produce drugs in their milk. He couldn't get the new genes into the embryo cells; he needed to be able to use later-stage or adult cells (they're more easily manipulated genetically). Mr. Willadsen had proven it was possible; Mr. Wilmut just had to figure out how to build on his predecessor's success. After lots of trial and lots of error, he did so, and in the summer of 1996, Dolly was born. She debuted on the world stage in February 1997.

But even that work has come under professional fire. Writing in January in the journal Science, two researchers questioned Dolly's scientific pedigree. They pointed out the experiment that produced Dolly actually began as work with fetal cells. Later, when Mr. Wilmut decided to try cloning an adult cell, he used a vial of sheep breast cells he had collected earlier and stored in his freezer as part of a different experiment. The critics suggested fetal cells and adult cells could easily have been intermingled under those circumstances.

Nevertheless, Mr. Wilmut has been touring over the past year, and his speeches show a cavalier attitude toward human life. "The embryo has the potential of becoming an individual person," he said last month in Philadelphia. "Some people think of the embryo as a little human.... [But] it is just a little ball of cells, and there is no possibility of a nervous system or consciousness."

Mr. Wilmut's answer to pro-life concerns: Find a way to create intrinsically defective clones-embryos that do not have the potential to survive.

That seems to be the thinking behind some other developments in the field of cloning. In recent months, researchers at the University of Texas and at the University of Bath have created headless mice and headless tadpoles. The gene that tells the body to produce the head was identified and switched off in 1,000 mouse embryos. Four mice were born; they died immediately because they had no way to breathe.

"It would almost certainly be possible to produce human bodies without a forebrain," Princeton biologist Lee Silver speculated in the London Sunday Times. "These human bodies without any semblance of consciousness would not be considered persons, and thus it would be perfectly legal to keep them 'alive' as a future source of organs."

The scenarios are starting to take shape: cloning as the ultimate form of tissue engineering.

Another significant technical advance is the cloning of one species with the egg of another species. Researchers say they've used cow's eggs, minus the nucleus, to clone sheep. Some believe a cow's egg could work for human cloning, drastically lowering the cost. The current practice of collecting human eggs involves hiring young women to submit to hormone injections that cause them to produce multiple eggs each month. That's expensive, especially for scientists who would expect a failure rate similar to Dolly's (277 tries, 1 success) or worse. But using cow's eggs could make it feasible.

There's one more advance of sorts that is worth noting. The vast potential for profit in this field has not gone unnoticed. In January, a Chicago scientist announced he will clone humans just as soon as he finds the cash to set up a laboratory. Richard Seed, a Harvard-educated physicist, says he needs about $2 million; he adds that he already has clients expressing interest. Mr. Seed dismisses his critics, who include President Clinton.

"New things of any kind, mechanical, biological, intellectual, always create fear," Mr. Seed told the Associated Press. "Then the subject becomes tolerated and ignored. And the third stage, which always happens, is the subject becomes enthusiastically endorsed, and I think the same thing will happen in human cloning.... I've said many times that you can't stop science; cloning and the reprogramming of DNA is the first serious step in becoming one with God."

And though he has been roundly condemned by the White House and pundits, and said by some other scientists to have more bark than bite, Mr. Seed does have supporters. A Swiss-based cult has offered to fund his research. The Raelians are a 40,000-member group that claims life on Earth was created (through cloning) by visiting aliens called the Elohim (Raelians borrow the Hebrew word from the first verse of Genesis). The resurrected Jesus was actually just a clone of the Jesus who was put to death, according to Raelian teaching.

The Raelians have set up a Bahamas-based company, Clonaid, and hired a University of Houston-trained scientific director. Dr. Brigitte Boisselier says she already has a list of clients and investors. The cult's leader, Rael (a former Canadian journalist named Claude Vorilhom) contacted Mr. Seed in January. The Swiss government takes the Raelians seriously; it passed a resolution last year branding the cult's cloning goals "monstrous."

Outlandish as these scenarios seem, the claims of more mainstream proponents of cloning are also grand. Cloning has been said to hold promise for those suffering from Parkinson's disease, muscular dystrophy, cancer, diabetes, osteoporosis, and aging.

But is there any scientific basis for those claims?

"No," says Dr. Rudd of the Christian Medical and Dental Society. "Those are just rhetoric, smokescreens. They sound good. Everyone wants there to be a cure for cancer."

The only foreseeable "cure" that cloning could offer for Parkinson's, for example, is creating a reliable source of stem cells for injection into sufferers' brains. And the ghoulish idea of putting an embryo into a person's head is not likely to win popular support for the procedure.

And what kind of help could cloning provide for cancer victims? One example is perfectly matched organs to replace those damaged by the disease; but that brings us back to those living organ farms.

There are legitimate uses for much of this technology, Dr. Rudd says. "We know that when we split a liver in half, both halves try to grow into whole livers, but only up to a certain point. If we could learn what switches them off, perhaps we could grow replacements. The key is to learn how to do these things without killing people-for that's what experimentation on human embryos is."

Dr. Rudd's Christian Medical and Dental Society is trying to help instruct scientists, physicians, and lawmakers. CMDS officials have made experts available to members of Congress who can give testimony at hearings and serve on fact-finding commissions; they've made the cloning issue a key component of their accredited continuing medical education seminars; and they've produced a research paper (see www.worldmag.com) touching on the scientific, ethical, and moral issues involved in cloning.

M.D. Anderson's Dr. Miller says the breakneck speeds of medical advances must not scare away Christians.

"It can be overwhelming," he says. "Plus, there's a lot of emotion, a lot of misconceptions, a lot of pseudoscience out there. But we've got to be involved in the discussions. We are the ones with the framework, with the understanding of the meaning of human life. We can't leave it to the medical community to regulate itself, and we can't leave it to government to regulate the researchers-are we going to look to the government for guidance on upright, ethical practices? Christians have to be involved."