By Dick Clapp

On December 1, NPR’s Living on Earth aired a segment on conflicts of interest in medical research. Host Bruce Gellerman interviewed Dr. Lennart Hardell, lead author of a recent article on conflicts of interest in cancer research published in the American Journal of Industrial Medicine, Catherine DeAngelis, editor-in-chief of the Journal of the American Medical Association, and me. On LOE’s website, there’s also a conversation between Gellerman and Dr. Dimitrios Trichopoulos, one of the researchers whom Hardell and his co-authors criticized in their article.

It’s instructive to examine Hardell’s allegations about Trichopoulos and Trichopoulos’s response, because both are fairly typical of the widespread dilemma of conflicts of interest in medical research.

As Dr. Hardell pointed out in his interview, industry-funded studies tend to show no adverse effects from exposures to their workers or products. Dr. Trichopoulos says that the research he does is not affected by who the funding source is, and even when he is summarizing what other researchers have done, his interpretation is not influenced by who pays for his summary. His actual practice in the dioxin example suggests otherwise.

Exponent Commissions Research for the Chlorine Industry
The consulting company Exponent, which is often employed by companies whose products are the subjects of lawsuits and proposed regulations, commissioned Trichopoulos and five others to write the report “Dioxin and Cancer.” The group was chaired by Dr. Jack Mandel, who was a Vice President of Exponent at the time. Trichopoulos told Gellermen that he didn’t know initially that the Chlorine Chemistry Council was funding the work, and that in general he doesn’t pay much attention to who Exponent’s clients are.

Exponent used the report in at least three instances. It was submitted by defendants in a lawsuit in Maine in August, 2000, over a year before the conference in Korea and three months before it was presented to the EPA Science Advisory Board by Dr. Trichopoulos. It was used by defendants (Kimberley-Clark and others) in the Maine lawsuit as evidence that pulp and paper mill waste containing dioxin posed no threat to those in a community where it was dumped and burned. The lawsuit was settled before going to trial.

In September of 2001, Trichopoulos presented the report at a dioxin conference in Korea. During his presentation, he did not specify the funding source for the report, and it was not mentioned in the official conference summaries. Trichopoulos told Gellerman that conference presentations usually do not go into detail about funding sources, and that, in any case, the report, including funding sources, was submitted for to the EPA shortly after the conference, and became available to the larger scientific community. He also said that the report’s tie to the industry “was obvious to everyone.”

Further information about the Korea conference in 2001 was revealed in a deposition of Jack Mandel, the Exponent Vice President. Dr. Mandel indicated that there was a lawsuit brought by Korean Vietnam veterans regarding health effects of Agent Orange and that this was going on at the time of the conference where he, Trichopoulos and other co-authors presented the Exponent report. Dr. Mandel was working for an American law firm representing the defendants at the same time.

On November 1, 2000, when Dr. Trichopoulos presented the Exponent report to the EPA Science Advisory Board subcommittee reviewing the EPA dioxin reassessment, he introduced himself at the Vincent L. Gregory professor at Harvard School of Public Health. I was a consultant to the EPA and attended the meeting; my notes at the time show that Trichopoulos made no reference to Exponent or the Chlorine Chemistry Council in his presentation. He said the epidemiology on dioxin and cancer was “null” and that one of the reasons the studies were not convincing is that “poor people” were exposed and this may be the reason for whatever excess cancer was observed. This comment took my breath away when he made it, as if being poor is either the cause of their cancer or some kind of uncontrolled confounder. Neither is true, of course. He also claimed that the International Agency for Research on Cancer, which called dioxin (TCDD) a human carcinogen in 1997, had to change its rules in order to make this determination. This was a false claim, as a subsequent presenter (Dr. Ellen Silbergeld) pointed out.

The Exponent group submitted a paper to Regulatory Toxicology and Pharmacology later that month (Cole P, Trichopoulos D, Pastides H, et al. Dioxin and Cancer: A Critical Review, Reg Toxicol Pharmacol 2003;38(3):378-388). Although peer-reviewed and modified, the journal article was essentially the same as the Exponent report. This article has been cited by 23 authors as of this date, including Dennis Paustenbach. The latter author cited the Exponent article in a review of the criteria for cleaning up dioxin-contaminated soil. The current editor of Regulatory Toxicology and Pharmacology is Gio Gori , who also has been associated with industry-oriented scientific work (for instance, see The Tobacco Documents).

Trichopoulos’s Handling of the Situation
In the Living on Earth interview, Dr. Trichopoulos said that he just sticks to the facts and that “Hardell is involved in litigation and wants to skew the data in one way or another.” He further indicates that it is only Hardell’s case-control studies that have shown increased cancer risk from dioxin exposure, and he gives specific references naming Hardell. He said in the interview that “we didn’t cite Hardell as an individual.” Both claims are false, and there are numerous other cohort and case-control studies showing increased cancer risk from dioxin exposure. In contrast, the National Academy of Sciences 1993 summary of Dr. Hardell’s studies found them consistent, well-done, and persuasive evidence of the carcinogenicity of herbicides and dioxin. (See “Agent Orange and the Veteran.” National Academy Press, 1993.)

On one level, Trichopoulos is guilty of an ad hominem attack on Hardell in the off-the-cuff comment in the interview, while claiming that his own work is somehow not involved in litigation. That might be simple hypocrisy and just another example of “men behaving badly.” But the problem goes deeper, I think, because of who Trichopoulos is and what he has done over the years. He was Chair of Epidemiology at Harvard for many years, and, like Sir Richard Doll, has received many awards and is recognized for his contribution to understanding the role of second-hand cigarette smoke in causing cancer. But he has also gone out of his way to minimize the effects of environmental and occupational carcinogenic exposures and has consistently testified in court cases and regulatory proceedings on behalf of industry clients. Dr. Trichopoulos also spoke at a meeting of the International Society for Environmental Epidemiology in which he dismissed the potential hazard of exposure to dioxin. So, he has a point of view that goes beyond simply reviewing the scientific literature, and he presents this point of view on behalf of clients. In spite of his claims to the contrary, his recent interview on “Living on Earth” mis-states the facts about his own practice.

Dick Clapp is Professor in the Department of Environmental Health at Boston University School of Public Health, and co-Chair of Greater Boston Physicians for Social Responsibility. He has a long-standing interest in the health effects of dioxin and has done research on Vietnam veterans, testified about dioxin before two Committees of Congress, and served as a plaintiffs’ expert witness in three jury trials involving dioxin.