Out of Sight, Out of Mind
by Brandon Keim

Not even the world's most prestigious place of learning is immune to the carelessness and disregard that grow where financial interests and academic inquiry meet without oversight.

In the early 1990s, the impoverished residents of China's remote Anhui province were believed to harbor a twenty-first century version of buried treasure: a large and homogeneous gene pool, isolated for two thousand years. Researchers hoped that the population’s relative uniformity would make it possible to link genetic mutations with diseases. Such information could ostensibly then be used to develop wildly profitable treatments. [For more on this rationale, see “The Genomics Dream in Iceland,” GeneWatch Volume 15 Number 4].

When Scott Weiss, a Harvard University respiratory epidemiologist, told Geoffrey Duyk, a geneticist who had left Harvard to join a biotechnology start-up called Millennium Pharmaceuticals, that one of his post-doctoral fellows came from the Anhui province, they quickly saw the possibilities. Harvard and Millennium announced a partnership: Weiss' fellow, Xu Xiping, would direct the collection of DNA in Anhui, for which Millennium would pay the University $3 million. From the blood of Anhui’s villagers, they believed, would come clues to the genetic causes of asthma, obesity, miscarriages, and schizophrenia.

Five months later, Swedish pharmaceutical giant Astra AB had swelled Millennium's accounts with a $53 million investment; the company would also receive $70 million from the pharmaceutical company Hoffmann-Laroche. In both cases, Millennium's access to the Anhui population’s DNA was critical to securing funding; the DNA’s potential was also featured prominently when Millennium went public in 1996, raising $54 million in its initial public offering.

In Anhui, where Xu's extensive connections allowed him to enlist the support of the local bureaucracy, residents were promised free medical care in exchange for blood samples. Later it became apparent that many subjects were not told what would be done with their blood. Often they were not even told that participation was a choice. Few who signed consent forms could actually read them. Given the political and social realities of China, Harvard’s disregard was tremendously risky; no protections exist in China for genetic discrimination by employers, and inhabitants of rural areas have limited legal recourse for their grievances. Chinese law also provides for sterilization of citizens who have unspecified genetic diseases of “serious nature.”

That law, in fact, was passed just a month before Harvard and Millennium announced their partnership. Many Western scientists then believed genetic research could not be safely conducted in China — but according to Weiss and Duyk, the issue was never discussed while planning research in Anhui. Incredibly, in one of Xu’s studies on reproductive genetics, he used the same government agency charged with limiting births to recruit subjects.

Over 95% of Anhui’s population had volunteered for the tests. However, it was not merely the promise of free medical care, or the failure to follow standard informed consent procedures, that produced these high numbers.

"If they don't want to participate," explained one doctor involved in the study, "officials go down to the villages and do thought work and move them to participate." These ominous words are given special significance by the brutal reality of the modern Chinese regime, especially in rural areas, where rogue Communist Party officers and corrupt local governments remain notoriously powerful. 'Thought work' is a polite term for coercion — which is itself a thinly veiled threat of terrifying repression. Testimonials of Chinese villagers exploited by unaccountable authorities are common.

Anhui's public security department quickly responded to reports of coercion by ordering researchers to stop talking to outsiders. Xu offered that the doctors who complained "now regret any untruthful answer they may have naively offered."

Xu, trading on his access to Anhui, would eventually receive $10 million from the NIH and March of Dimes. Little wonder that he claimed ignorance when confronted with evidence of mistreatment of test subjects. Harvard and Millennium also feigned innocence; Duyk attributed the high rate of volunteerism to simple yokel curiosity. "It was fun for people," he said. "Just to participate in it was an interesting thing."

In 1999, after a Harvard whistleblower contacted the Department of Health and Human Services, the university sent a six-member review team, including Weiss and Xu, to Anhui. Their findings resembled the glowing reports from Western journalists given official tours of Stalin-era Soviet labor camps. James Ware, the Dean of Harvard's School of Public Health, said the Chinese the team met were "clean and well-dressed," and the "notion of an oppressed, malnourished or illiterate population" was at odds with what they saw.

The Department of Health and Human Services, however, was rather less credulous. In March 2002, two years after the Washington Post published a comprehensive investigation of Harvard’s activities in Anhui, the federal Office for Human Research Protections (OHRP) issued a scathing indictment of the University’s research. The OHRP found that Harvard failed to have many of its Anhui studies approved by institutional review boards; where approval had been granted, significant and unannounced changes were often made. Harvard was charged withfailing to minimize risks to their subjects. In the end, subjects never even received the free medical care they had been promised.

Harvard's apology came quickly and predictably. "We have revised in a drastic way all of our procedures for research at the public health school," University President Lawrence Summers told Chinese students after a Boston Globe article on the OHRP's findings. "The interests of individual human beings should never be sacrificed to some concept of abstract scientific inquiry."

Summers' response, appealing to the public's belief in the sanctity of science, was telling in its refusal to acknowledge what actually happened, and provided scant reason to believe the institution has truly changed. It was for tangible financial gain, not ‘abstract scientific inquiry’, that Harvard sacrificed the rights of its test subjects.

Brandon Keim is Director of Communications at the Council for Responsible Genetics.