Harvard genetic research in rural China

Alliance for Human Research Protection (AHRP), Press Release, 2 October 2003

http://www.ahrp.org
Contact: Vera Hassner Sharav
Tel: 212-595-8974
e-mail: veracare@ahrp.org

It's the responsibility of the dean of the School of Public Health and, ultimately, it's my responsibility as president of [Harvard] university to see to it that where wrong can be put right it is and, more importantly, to see to it that it never happens again.

Lawrence Summers, (Boston Globe, 2002)

But a disturbing investigative report by senior CHINA DAILY reporters who conducted an on-site investigation of the controversial genetic experiments conducted by scientists from the Harvard School of Public Health (HSPH) in rural China, reveals that nothing has been put right, notwithstanding Harvard University's self-proclaimed exoneration of its faculty members. The experiments were co-sponsored by the US government and Millenium Pharmaceuticals and were conducted in Zongyang County, in East China's Anhui Province, in the mid 1990s, on mostly illiterate Chinese farmers, who it appears were exploited and experimented on without informed consent—a fundamental, universally recognized human right.

Complaints about the ethics of several of these experiments were filed by Dr. Gwendolyn Zahner, an epidemiologist who had conducted on-site inspections. Her first complaint (in 1999) led to a US federal investigation by the Office of Human Research Protections (OHRP), an agency whose current and past directors are affiliated with Harvard University.

In the course of its investigation, OHRP issued 3 letters (March 28, 2002) to the Harvard affiliated research centers involved: Harvard School of Public Health (HSPH), Brigham and Women's Hospital (B&WH), and Mass. Mental Health Center (MMHC). The OHRP letters described gross multiple violations in a dozen experiments demonstrating a disregard for the rights, dignity and welfare of vulnerable, illiterate human subjects. In particular, OHRP cited:

the investigators' failure to obtain institutional review board (IRB) approval for every study and for every change in the research; failure to minimize risks for subjects; and failure to fully disclose to the subjects their rights to refuse to participate without consequences—as required under the Code of Federal Regulations. OHRP found that:

• Signatures on informed consent documents raised concerns that they were post dated.
• The number of subjects recruited seemed to bear no relationship to the number approved by the IRB.
• In an Asthma study, the B&WH IRB approved the enrollment of 2,000 subjects. However, the investigator enrolled 16,686 subjects.
• Informed consent documents were altered without IRB approval: for example, the amount of blood drawn was changed from two teaspoons to six.
• In some cases, Harvard officials reported to OHRP that a given study had not been conducted, but OHRP cited recent publications in which the investigators described the findings of that study.
• In another case, the HSPH IRB did not review an asthma study until 3 years after it had been submitted.

See OHRP letters, March 28, 2002:
http://ohrp.osophs.dhhs.gov/detrm_letrs/YR02/mar02a.pdf
http://ohrp.osophs.dhhs.gov/detrm_letrs/YR02/mar02b.pdf
http://ohrp.osophs.dhhs.gov/detrm_letrs/YR02/mar02c.pdf

These serious findings prompted Harvard's president, Lawrence Summers, to go to China in May, 2002, where he expressed deep regret that a dozen Harvard-run genetic studies in China failed to give test subjects adequate information about potential pitfalls:

What happened was wrong and it was badly wrong. It's the responsibility of the dean of the School of Public Health and, ultimately, it's my responsibility as president of the university to see to it that where wrong can be put right it is and, more importantly, to see to it that it never happens again.

Summers assured a group of students at Peking University that the Harvard School of Public Health had revised its research procedures drastically, and affirmed that:

The interests of individual human beings should never be sacrificed to some concept of abstract scientific inquiry.

However, despite the egregious ethical violations that were confirmed by OHRP, the agency's investigation did not include a site visit to China by agency officials.

Instead, OHRP asked Harvard to investigate itself, including new allegations of fraud contained in a June 19, 2002 letter from an anonymous complaint in China.

The letter, according to OHRP,alleged that:

Dr. Xu directed Chinese researchers and employees to forge informed consent documents for several studies. OHRP deferred investigation of the allegation to Harvard.

Understandably, Harvard shielded itself and its faculty, stating it found no evidence to substantiate the allegations. OHRP's failure to conduct an independent investigation, relying entirely on documents and reports submitted by Harvard, raises serious questions about the agency's credibility and fairness.

OHRP's failure to exercise its investigatory authority enabled Harvard to protect its financial interests in the China studies. Indeed, OHRPs final letter of determination (May 2, 2003) disregards the agency's own documented findings (March 28, 2002) of noncompliance with federal human protection requirements, and disregards the rights and dignity of thousands of Chinese people who were summoned by a totalitarian regime, presumably for free check ups.

Families were bled, allegedly without explanation of the experimental purpose for drawing their blood or that they have a right to refuse.

OHRP's 2003 letter of determination states: the informed consent document for the study 'Organophosphate pesticide exposure and reproductive toxicity' may have failed to include information about genetic testing of subjects' blood.

Yet, OHRP accepted Harvard's vague promises without reservation:

HSPH has been planning, in cooperation with colleagues in China, to conduct real-time consent monitoring of the two projects that Dr. Xu plans to resume when OHRP's investigation is complete.

OHRP's letter of determination has done nothing to quell the controversy, or to deter investigators affiliated with influential academic institutions from disregarding human rights on an international scale.

Government agencies who award licenses to institutions conducting human research should not turn a blind eye to gross human rights violations in underdeveloped countries by institutions it licenses.

Following the OHRP letter, Harvard claimed in its newsletter (May 2003) that a thorough fact-finding inquiry could not substantiate the allegations. See:

http://ohrp.osophs.dhhs.gov/detrm_letrs/YR03/may03b.pdf

This claim led China Daily's senior reporters, Xiong Lei and Wen Chihua, to conduct their own independent fact-finding investigation. They interviewed the farmers in Anhui and a local medic who had been ordered to produce a list of asthmatic villagers and their families. Zhang Da'niu who suffers from asthma, was among those villagers who went for what he thought was a free check up when summoned for epidemic prevention control.

But instead of medical care, Zhang says he was doused with a fog-like agent in a spray can that nearly killed him: Half way into the process...he became out of breath and then lost consciousness.

Zhang and his wife claim the doctors provided no medical treatment beyond initial emergency care, even though he was very ill. One doctor promised to send medicine but it never came. Zhou told China Daily, He did not ask for our address and I assumed he should know through the official who called us in for the check-up.

Furthermore, Zhang Funian (the medic) confirms what the villagers claim:

We were told to notify villagers with asthmatic symptoms to have a physical check-up in town.

We were told the check-up would benefit them, and free medical treatment would be offered.

The medic also confirms that to his knowledge, none of the farmers was told of the procedures and results of the 'check-up,' or saw a copy of any informed consent forms.

They claim no one explained the purpose or use of the blood samples taken from family members.

Asthma is one of more than a dozen genetic projects drawing the Harvard research team to sample Chinese farmers' blood for genetic screening to find hereditary links to diseases ranging from asthma to hypertension, obesity, diabetes, schizophrenia and osteoporosis, as well as reproductive outcomes from exposure to petrochemicals, lead, and organophosphate pesticide.

China Daily cites published articles by the primary investigator, Xu Xiping and colleague, Scot T. Weiss, published in The Journal of Respiratory and Critical Care Medicine (JRCCM) that state they had conducted a large genetic epidemiologic study in Anqing, China, to examine the contributions of environmental and genetic factors to asthma. The survey, they state, was conducted between July 1, 1994 and January 26, 1998.

But OHRP noted inconsistencies regarding the date when the asthma experiment began and the date it was approved by a Harvard-affiliated IRB. China Daily lays out detailed documented inconsistencies. In 2003, three years after publications, Xu and Weiss posted corrections in JRCCM for a total of seven scientific research articles stating that their respiratory research in China began in February 1995 with approval from a local IRB.

However, press releases (1995) by Millenium Pharmaceuticals, which sponsored the asthma tests, and the Harvard School of Public Health imply that the tests were well under way in 1995.

And in a Dec. 1999 letter addressed to Dr. Greg Koski, Xu states that his institute submitted a Human Subjects application through the B&WH Human Research Committee to conduct the formal study in October 1994, and this was finally approved in September 1995, so the formal collaborative study began in October 1995.

(Dr. Koski was at the time director of Human Research Affairs at Partners Health Care System, which owns and operates the Harvard-affiliated B&WH and Massachusetts General Hospital).

As China Daily notes: Whatever the explanations, what went on didn't accord with the facts nor was it consistent with the ethical principles the Harvard institutions commit themselves to observing.

The Harvard Chinese genetic experiments have been the subject of critical reports in the US and international press. The problem for uneducated, powerless peasants living in rural China, are confounded by a totalitarian regime whose elite scientists have been so eager to seek international co-research projects accompanied with funds that they've ignored the ethical issues involved, especially the issues concerning the protection of the rights of the farmers who are the subjects of the projects.

There was a saying during the Communist era that applies to the human research enterprise:

The difference between Capitalism and Communism is that in Capitalist countries man exploits man and in Communist countries it is the exact opposite.

Because we, of The Alliance for Human Research Protection, recognize that human nature is what it is, and powerful members of the elite will always seek ways to exploit the vulnerable among us, the civilized world needs the force of law to ensure that the human rights enshrined in The Nuremberg Code are enforced.

The voluntary consent of the human subject is absolutely essential.