Of Clones and Clowns

A distinguished molecular biologist discusses the "cloning circus" and the damage it is doing to serious research
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Biologists have been rather silent on the subject of human cloning. Some others would accuse us, as they have with predictable regularity in the recent past, of insensitivity to the societal consequences of our research. If not insensitivity, then moral obtuseness, and if not that, then arrogance—an accusation that can never be disproved.

The truth is that most of us have remained quiet for quite another reason. Most of us regard reproductive cloning—a procedure used to produce an entire new organism from one cell of an adult—as a technology riddled with problems. Why should we waste time agonizing about something that is far removed from practical utility, and may forever remain so?

The nature and magnitude of the problems were suggested by the Scottish scientist Ian Wilmut's initial report, five years ago, on the cloning of Dolly the sheep. Dolly represented one success among 277 attempts to produce a viable, healthy newborn. Most attempts at cloning other animal species—to date cloning has succeeded with sheep, mice, cattle, goats, cats, and pigs—have not fared much better.

Even the successes come with problems. The placentas of cloned fetuses are routinely two or three times larger than normal. The offspring are usually larger than normal as well. Several months after birth one group of cloned mice weighed 72 percent more than mice created through normal reproduction. In many species cloned fetuses must be delivered by cesarean section because of their size. This abnormality, the reasons for which no one understands, is so common that it now has its own name—Large Offspring Syndrome. Dolly (who was of normal size at birth) was briefly overweight in her young years and suffers from early-onset arthritis of unknown cause. Two recent reports indicate that cloned mice suffer early-onset obesity and early death.

Arguably the most successful reproductive-cloning experiment was reported last year by Advanced Cell Technology, a small biotech company in Worcester, Massachusetts. Working with cows, ACT produced 496 embryos by injecting nuclei from adult cells into eggs that had been stripped of their own nuclei. Implanting the embryos into the uteruses of cows led to 110 established pregnancies, thirty of which went to term. Five of the newborns died shortly after birth, and a sixth died several months later. The twenty-four surviving calves developed into cows that were healthy by all criteria examined. But most, if not all, had enlarged placentas, and as newborns some of them suffered from the respiratory distress typical of Large Offspring Syndrome.

The success rate of the procedure, roughly five percent, was much higher than the rates achieved with other mammalian species, and the experiment was considered a great success. Some of the cows have grown up, been artificially inseminated, and given birth to normal offspring. Whether they are affected by any of the symptoms associated with Large Offspring Syndrome later in life is not apparent from the published data. No matter: for $20,000 ACT will clone your favorite cow.

Imagine the application of this technology to human beings. Suppose that 100 adult nuclei are obtained, each of which is injected into a human egg whose own nucleus has been removed. Imagine then that only five of the 100 embryos thus created result in well-formed, viable newborns; the other ninety-five spontaneously abort at various stages of development or, if cloning experiments with mammals other than cows are any guide, yield grossly malformed babies. The five viable babies have a reasonable likelihood of suffering from Large Offspring Syndrome. How they will develop, physically and cognitively, is anyone's guess. It seems unlikely that even the richest and most egomaniacal among us, intent on recreating themselves exactly, will swarm to this technology.

Biological systems are extraordinarily complex, and there are myriad ways in which experiments can go awry or their results can be misinterpreted. Still, perhaps 95 percent of what biologists read in this year's research journals will be considered valid (if perhaps not very interesting) a century from now. Much of scientists' trust in the existing knowledge base derives from the system constructed over the past century to validate new research findings and the conclusions derived from them. Research journals impose quality controls to ensure that scientific observations and conclusions are solid and credible. They sift the scientific wheat from the chaff.

The system works like this: A biologist sends a manuscript describing his experiment to a journal. The editor of the journal recruits several experts, who remain anonymous to the researcher, to vet the manuscript. A month or two later the researcher receives a thumbs-up, a thumbs-down, or a request for revisions and more data. The system works reasonably well, which is why many of us invest large amounts of time in serving as the anonymous reviewers of one another's work. Without such rigorously imposed quality control, our subfields of research would rapidly descend into chaos, because no publicly announced result would carry the imprimatur of having been critiqued by experts.

We participate in the peer-review process not only to create a sound edifice of ideas and results for ourselves; we do it for the outside world as well—for all those who are unfamiliar with the arcane details of our field. Without the trial-by-fire of peer review, how can journalists and the public possibly know which discoveries are credible, which are nothing more than acts of self-promotion by ambitious researchers, and which smack of the delusional?

The hype about cloning has made a shambles of this system, creating something of a circus. Many of us have the queasy feeling that our carefully constructed world of science is under siege. The clowns—those who think that making money, lots of it, is more important than doing serious science—have invaded our sanctuary.

The cloning circus opened soon after Wilmut, a careful and well-respected scientist, reported his success with Dolly. First in the ring was Richard Seed, an elderly Chicago physicist, who in late 1997 announced his intention of cloning a human being within two years. Soon members of an international religious cult, the Raëlians (followers of Claude Vorilhon, a French-born mystic who says that he was given the name Raël by four-foot-high extraterrestrials, and who preaches that human beings were originally created by these aliens), revealed an even more grandiose vision of human cloning. To the Raëlians, biomedical science is a sacrament to be used for achieving immortality: their ultimate goal is to use cloning to create empty shells into which people's souls can be transferred. As a sideline, the Raëlian-affiliated company Clonaid hopes to offer its services to couples who would like to create a child through reproductive cloning, for $200,000 per child.

Neither Seed nor the Raëlians made any pretense of subjecting their plans to review by knowledgeable scientists; they went straight to the popular press. Still, this wasn't so bad. Few science journalists took them seriously (although they did oblige them with extensive coverage). Biologists were also unmoved. Wasn't it obvious that Seed and the Raëlians were unqualified to undertake even the beginnings of the series of technical steps required for reproductive cloning? Why dignify them with a response?

The next wave of would-be cloners likewise went straight to the mainstream press—but they were not so easily dismissed. In March of last year, at a widely covered press conference in Rome, an Italian and a U.S. physician announced plans to undertake human reproductive cloning outside the United States. The Italian member of the team was Severino Antinori, a gynecologist notorious for having used donor eggs and in vitro fertilization to make a sixty-two-year-old woman pregnant in 1994. Now he was moving on. Why, he asked, did the desires of infertile couples (he claimed to have 600 on a waiting list) not outweigh the concerns about human cloning? He repeatedly shouted down reporters and visiting researchers who had the temerity to voice questions about the biological and ethical problems associated with reproductive cloning.

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