Of Clones and Clowns

A distinguished molecular biologist discusses the "cloning circus" and the damage it is doing to serious research

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.

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