Commentary Magazine


Lessons of the Cloning Scandal

By now most well-informed people know the sorry tale of Hwang Woo Suk, the South Korean veterinarian who rose to scientific superstardom as a pioneer of cloning—and who fell just as quickly when it came to light that his “breakthroughs” had mostly been fabricated, and rather sloppily at that. Hwang, who had been awarded the title of “supreme scientist” and an annual grant of some $3 million by the South Korean government, has now been suspended from his chair at Seoul National University (SNU), and his numerous collaborators face varying degrees of censure.

The facts of the case are relatively straightforward. In February 2004, Hwang surprised the world when he announced that he and his team had created human embryonic stem cells from donor eggs. The announcement was followed by the publication of a report in the American journal Science, in which Hwang and his colleagues described how they had extracted the nucleus of an adult cell and inserted it into an egg cell from the same donor whose own nucleus had been removed. They then purportedly coaxed the egg cell to divide until it yielded embryonic stem cells—a trick that succeeded after 242 attempts. In layman’s terms, this was the first report of successful human cloning.

Whatever its moral implications, from a scientific standpoint this was no trivial achievement. Although Dolly the sheep had been born in 1996, shattering the assumption that mammals could not be cloned, many developmental biologists felt that it would be much harder to clone humans because of quirks in the way our chromosomes are modified during the normal development of sperm and egg cells. Hwang’s team seemed to show not only that somatic-cell nuclear transfer (the technical term for cloning) worked with humans, but that the procedure was relatively efficient, requiring far fewer donor eggs than had previously been thought possible.

A year later, in May 2005, Hwang announced a second coup: the creation of eleven different stem-cell lines, using embryos cloned from the genetic material of people of different ages and genders. Another supporting paper in Science soon followed. If the first paper represented an important advance, the second was a marvel, holding out the possibility of creating custom-tailored embryonic stem cells for patients suffering from ailments like diabetes and Parkinson’s disease. Therapies developed from such cells would skirt the potential problem of immune rejection. Indeed, Hwang suggested that the technique might soon be ready for therapeutic application. To top it all off, he declared in August that his team had been the first to clone a dog, an Afghan hound christened Snuppy (for Seoul National University puppy).

In retrospect, Snuppy may have been the dog that broke the camel’s back: the feat propelled Hwang to new heights of fame, but the attention brought with it greater scrutiny. The first whiff of something rotten aired in November 2005, when Hwang’s American collaborator Gerald Schatten, a biologist at the University of Pittsburgh, sought to dissociate himself from the Korean team, citing ethical concerns about how the donor eggs were obtained. Subsequent revelations—that individual donors had been paid as much as $1,400, and that some of the eggs had come from one of Hwang’s graduate students—suggested that the work had been done in flagrant violation of international research norms.

Hwang’s defenders in South Korea dismissed these concerns as alien to Korean society, and denounced investigations into the issue as “unpatriotic.” But the dike had already broken. Skeptical scientists pointed out that some of the figures accompanying Hwang’s second Science paper appeared to be duplicates of one another. Some American biologists proposed that outside scientists be allowed to examine Hwang’s materials; he declined to cooperate. By January 2006, a panel of investigators at SNU had determined that there was no evidence to support any of Hwang’s claims about human cloning. The only real clone produced by the SNU lab turned out to be Snuppy.

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Though by now the furor has largely subsided, there seems to be a lingering uncertainty about what lessons, if any, to draw from the Hwang affair. Almost everyone agrees that the revelation of his deception has not closed the book on his line of research. As David Shaywitz, an endocrinologist at the (privately funded) Harvard Stem Cell Institute, wrote in a New York Times op-ed, understanding the complex biology of stem cells might “take a very long time,” but “stellar science” is still being done, and the field is too promising to be abandoned. Shaywitz’s colleague Douglas Melton, a developmental biologist, told the Washington Post that “[w]hat happened in Korea hasn’t sped up or slowed down our progress.”

Nor do editors of prominent scientific journals seem very concerned. Though they have promised to screen high-profile submissions more carefully in the future, most seem to believe that this sort of thing just happens from time to time. The editor of Science, Donald Kennedy, told an audience at Stanford University that “scientific fraud is not new,” and that he did not “think any reviewer could detect fraud if it was carried out by a capable scientist who knows how to walk the walk.”

As for general-interest reporting on these issues, Laura Chang, science editor of the New York Times, admitted that most major newspapers turn to respected journals for their science news, relying on them to decide not only what constitutes good research but also what kind of research is exciting and important. “That will not change,” she matter-of-factly told a reporter from her own paper.

Indeed, some have suggested that the Hwang scandal is little more than a particularly outrageous example of the kind of fraud that occurs in all human endeavors. According to this view—one might call it the “bad apple” theory—most scientists are diligent, honest, and objectively-minded seekers of knowledge. Every so often, however, one of them decides to skip the research stage and simply fabricate his results, motivated by the promise of fame or the conviction that his ideas are so important that he should not have to bother with the messy work of gathering data. Such a scientist may get away with deception in the short term, but he will eventually be caught: someone will raise questions, or a co-worker will come clean, or other researchers will fail to replicate his results, thereby raising suspicions of fraud or incompetence. The cheater will face disgrace, and the honest scientists will return to business as usual.

The most important implication of this view is that we should not let an occasional scandal lead us to question the scientific enterprise or its practitioners. This was the thrust of a Washington Post editorial by the Yale historian Bettyann Holtzmann Kevles, who pointed to infamous incidents like the Piltdown hoax and the swindle of William Summerlin—a physician who, in 1974, tried to pass off ink blots on the backs of white mice as patches of skin tissue transplanted from unrelated black-skinned mice.

There are more recent illustrations as well. Just a few years ago, in 2002 and 2003, the journals Science and Nature between them withdrew 15 papers authored by Jan Hendrik Schön, a German scientist working at Bell Labs who fraudulently claimed to have made groundbreaking discoveries in the physics of nanoscale transistors. Despite Schön’s malfeasance, the field of nanotechnology is still flourishing, even if it no longer appears that a revolution in electronics is just on the horizon.

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That said, the “bad apple” theory all too conveniently exculpates the enablers of scientific fraud, namely, the major scientific journals and their criers in the popular press. It is probably true that a meticulous cheat can produce results so realistic that they would be impossible to expose until other scientists failed to reproduce them. Curiously, however, this is not what scientific fraud usually looks like; most examples of fake data are astoundingly shoddy. Like Hwang, Schön was caught when it was noticed that his results seemed too good to be true—and that he had used the same graph for three different experiments. In both cases, moreover, outside scientists rang alarm bells shortly after the fraudulent data were published, which raises the question of how the cheaters advanced as far as they did.

It is well known among scientists that the most prestigious journals—like Science, Nature, and the New England Journal of Medicine—sometimes base their selection of articles on factors that can have little to do with the quality of the research they report. Benjamin Lewin, a geneticist and scientific entrepreneur who founded the almost as prestigious journal Cell, put it bluntly when he told the New York Times that “Nature and Science don’t have the reputation for rigorous review.”

When papers arrive at the editorial offices of these journals, they are first vetted for their potential impact: if a paper is deemed insufficiently interesting, it is returned to the authors with the suggestion that they try their luck with a more pedestrian journal. If the editors decide that a paper is interesting enough to warrant peer review, its fate may still depend less on its merits than on how strongly they feel about publishing it. A paper on a “hot” topic, with high potential impact, might be sent to a few reviewers likely to be friendly; by contrast, a solid paper on a less fashionable topic might be subjected to a higher degree of scrutiny.

In the past few years, stem-cell research has been among the hottest of hot fields, for political as well as scientific reasons. The editors of the New England Journal of Medicine announced in 2003 that they would make a special effort to seek out “highly meritorious manuscripts” on embryonic stem-cell research and somatic-cell nuclear transfer—partly because they were interested in undermining “unreasonable” legislative efforts to restrict such research. In other words, the journal was expending some of its prestige to advance a particular agenda. Shaywitz, the Harvard endocrinologist, conceded that “the bar for publication in this field often has appeared remarkably low, with even well-respected research journals seeming to fall over one another for the privilege of publishing the next hot paper.”

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This leads to a second take on the Hwang fiasco, which one might call the “hope and hype” hypothesis (a term I borrow from the title of Shaywitz’s op-ed piece). This view holds, essentially, that science is ill-served by unrealistic expectations. The excitement about stem cells, for example, no doubt has much to do with the promise they appear to hold for the treatment of devastating diseases—a promise that has been greatly exaggerated in the popular mind. Newspaper articles about stem-cell research inevitably mention that discoveries in the field might one day lead to such cures. Although he was later ridiculed by commentators, Senator John Edwards sounded credible to many Americans when, as a candidate in 2004, he declared that stem-cell research would soon enable quadriplegics like Christopher Reeve to “get up out of that wheelchair and walk again.” Hwang himself made a similar claim for the stem-cell therapies that would result from his cloning research, and his pledge was inscribed on a South Korean postage stamp. Such hype creates an environment that invites opportunistic fakery.

There is nothing inherently dishonest, of course, about the claim that embryonic stem-cell research and therapeutic cloning could lead to remarkable advances in treating disease; they just might. It is worth keeping in mind, however, that other seemingly promising avenues for treatment have shown themselves to be ridden with stumbling blocks. Over the last two decades, we have heard a great deal, for example, about the potential of gene therapy—the idea that a person suffering from a certain disease because of a missing or defective copy of a particular gene could be treated by having a new, functional copy inserted into his cells. But the field has advanced very slowly since the death of an eighteen-year-old man during a clinical trial in 1999. Research on another initially successful gene therapy for an immune-deficiency syndrome was halted in 2003 when it was found that the treatment might lead to leukemia.

A surfeit of hype also opens the door to slipshod research that can tarnish the reputation of entire fields. Following the development of new techniques in molecular genetics in the 1980′s and early 90′s, the popular press was filled with reports that biologists had discovered genes “for” everything from extroversion to homosexuality—claims of a sort encountered much less frequently these days. Likewise, the advent of noninvasive brain imaging about a decade ago unleashed a slew of quasi-phrenological “discoveries” about areas of the brain that supposedly underlie various aspects of human thought.

Still, for all the value of calls for scientific modesty, it is hard to see what would motivate many scientists if they did not think they were working to find big solutions to big problems. When researchers say that an answer is tantalizingly close, the chances are that they believe it, even if what they mean by “close” is that they hope to succeed after a lifetime of painstaking experimentation. A bit of exaggeration is to be expected—without it, fewer scientists would attempt ambitious research, and less money would be available to fund it.

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If excess hype and misplaced hope are one part of the explanation for the Hwang episode, a deeper cause lies in the power of ideology in science. It is hardly a revelation that scientists, like everyone else, have ideological commitments that sometimes influence their judgment. “Ideological,” it should be said, is not always synonymous with “political”: heated scientific debates can break out over topics of no obvious social relevance, like whether turtles are more related to birds or lizards, or whether the brain possesses inherent rules for acquiring grammar (I think it does, a matter on which I happen to agree with Noam Chomsky, whose political views are quite different from my own). Such debates can sometimes provide the intellectual fuel for highly productive lines of research.

It is a cause for concern, however, when ideological commitments get in the way of free inquiry instead of advancing it. When the editors of the New England Journal of Medicine declare their intention to promote embryonic stem-cell research, they send a signal to funding bodies that such research should take priority over less favored subjects. One casualty of this campaign has been work on adult—as opposed to embryonic—stem cells.

There are, to be sure, plenty of problems with adult stem cells, not least that they are less versatile, and thus less potentially useful, than their embryonic counterparts. But embryonic cells are also tricky to work with, and it has been suggested that they may be more susceptible to harmful mutations—which, quite properly, does not seem to have dampened the enthusiasm of many biologists working on them.

So why has research on embryonic cells been favored in the journals and by many scientists over research on adult cells? Much of the answer, unfortunately, is purely political: because any success in adult stem-cell research would give ammunition to the (often religious) opponents of the embryonic kind. Worse, from the point of view of growing numbers in the scientific community, such work is favored by President Bush, who decided in 2001 to withhold government funding from research involving newly created embryonic stem-cell lines and subsequently endorsed a moratorium on cloning. In these circumstances, when a prominent biologist declares that research on adult stem cells is a sideshow or a dead-end, it is difficult to believe that his assessment is based on science rather than dogma.

Similar problems can be seen in other highly politicized scientific debates. The editor of Science, Donald Kennedy, who happens to have run the Food and Drug Administration under President Carter, has lately been an outspoken critic of scientists who voice skepticism about global warming. Kennedy is certainly entitled to his opinion, and he can cite empirical research to back up his argument. He has also claimed that Science simply does not receive any credible manuscripts that challenge the prevailing view, a statement that some have interpreted as evidence that the matter has been settled conclusively. But is it any wonder that scientists who harbor doubts about the global-warming hypothesis do not bother to send their papers to Science, where they will be summarily rejected—or perhaps do not pursue research in climate change at all, since they would have a better chance of publishing in prestigious journals (and winning research grants) in other areas?

Because the structure of academic science automatically gives the upper hand to majority opinion, a dominant ideology, once established, is hard to overturn. When the Danish statistician Bjørn Lomborg published The Skeptical Environmentalist in 2001, marshalling reams of data to suggest that common claims about global warming and other supposed environmental woes were unsubstantiated, he was showered with scorn by prominent environmental scientists, including in the pages of Science—and hauled before an investigative panel under Denmark’s Ministry of Science, Technology, and Innovation on charges of scientific misconduct. Lomborg was exonerated, and the case was closed in 2004. But the perception of a scandal has encouraged many scientists, not to mention the mainstream media, to ignore his work.

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The public credibility of science depends to some degree on the willingness of scientists to reject absolutist claims about what kinds of concerns are valid and important, and what kinds are not. The problem has long been familiar within the scientific community: inflexible paradigms tend to promote research that upholds the consensus view while impeding innovation and making it hard to pursue dissenting ideas.

In today’s more science-savvy world, however, curbing the influence of scientific dogma is not just an internal affair. In a survey conducted by the University of Chicago’s National Opinion Research Center in 2000, 41 percent of respondents reported that they had a great deal of confidence in the leadership of the scientific community—putting scientists ahead of educators and just behind doctors on this measure. But such confidence seems to be linked to the perception that scientific researchers work strictly for the good of humanity, staying out of politics and other divisive arenas.

Should this perception change, public confidence in science may slip, just as confidence in the medical establishment has eroded over the past 30 years as health-care issues have become increasingly politicized. It may become correspondingly harder for scientists to influence social debates in which they have a genuine stake. If researchers’ pronouncements about contentious issues like global warming and stem cells are seen to be ideologically motivated, it will be that much more difficult to persuade the public that a theory like Intelligent Design does not merit attention in the realm of science.

The stem-cell scandal reminds us not only that we need to take the judgment of even the most esteemed experts with a grain of salt but also that science, far from being a purely objective pursuit, is colored by the predilections and biases of its practitioners. Empirical truth is still out there to be discovered, and scientific induction—susceptible as it may be to error, prejudice, and fraud—is still the best means we have to discover it. But what truth we discover depends, very often, on where we decide to look for it.

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About the Author

Kevin Shapiro is a research fellow in neuroscience and a student at Harvard Medical School.




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