R. Palmer Beasley

So contends R. Palmer Beasley, newly retired dean of the University of Texas–Houston Health Science Center, who persisted through many years of criticism and disbelief in the 1970s before showing beyond a doubt that the hepatitis B virus (HBV) causes liver cancer.

Beasley delivered the 141st Cutter Lecture last month in Snyder Auditorium. At the close of 2004, he ended a two-year term as the national chairman of the Association of Schools of Public Health.

At the time of Beasley’s research–which also showed that mother-infant transmission was the most important factor in sustaining HBV infection in Asia–few scientists believed human viruses could cause cancer. His suggestion that the HBV could lead to liver cancer "was a nutty, unpopular idea," Beasley said in his talk. "It was generally thought that liver cancer patients had immunologic problems, becoming carriers as a result of the cancer," instead of the reverse.

Although he ultimately proved his case with a now-famous large cohort study that won him numerous honors, Beasley came away deeply concerned that epidemiologic research was being hampered by confusion over which criteria are essential to clinch proof of causality.

In the 1890s, Robert Koch, a German scientist, published his postulates for proving a pathogen’s role in an infectious disease. A scientist had to show that the suspect bug was present in diseased cases but not in healthy controls; could be grown in laboratory cultures; and could be reproduced when inoculated into experimental animals. These rules, designed for "the 1890 microbial world," said Beasley, are clearly too restrictive when scientists are confronted with the delayed effects of tobacco smoke, toxic agents, radiation, slow viruses, and other agents. In 1965, noted epidemiologist Sir Bradford Hill proposed an updated and expanded list of "viewpoints," which others have dubbed criteria, not all of which must be fulfilled to establish scientific causation. The viewpoints have been in widespread use for more than 30 years.

The Hill viewpoints include strength of association; consistency and unbiasedness of findings; temporal sequence (exposure must occur before disease onset); dose-response relationship; specificity; biological plausibility; coherence with previous knowledge; and reasoning by analogy. A particular problem is that Koch’s postulates are so narrowly specified that most people cannot understand them in relation to Hill. On the other hand, not all of the Hill viewpoints are equally usable. They need to be reworked and prioritized, according to Beasley.

No set of criteria will be able to identify all cause-and-effect relationships, Beasley cautioned. For example, he said, undramatic agents that leave no footprints and take a very long time to produce infrequent disease may well go undetected forever.

Still, he believes the best course is to put the Hill viewpoints–not all to which he agrees–together with Koch’s postulates in a broader context and conduct a discussion that spans scientific, legal, and public policy communities. This goal has been occupying him of late, particularly as he observes environmental litigation that could lead, in his mind, to wrongheaded public policy. Rather than using the courts to try to deal with very complex scientific issues, Beasley believes that there should be expert panels convened on a case-by-case basis, perhaps established by the Institute of Medicine or the National Institutes of Health.

While raising the question of what authority or forum should consider cases like this–some sort of "science court"–Beasley said that the first order of business is to reconcile changing and confusing criteria for evaluating causality, beginning with reconciling Koch and Hill

"We need criteria," he said, "because most people aren’t organized enough to go through all the thinking processes on their own, and the world needs to have something from which to work."

--RS