Response: alpha-2-mu-Globulin Nephropathy, Posed Mechanisms, and White Ravens.

Woodward and Goodstein (1) discussed the handling of data that do not support a given hypothesis. They illustrated their point as follows: an investigator might inductively infer, after observing a large number of black ravens, that all ravens are black. According to the inductive approach, good scientific practice consists in recording all that one observes and not just some selected part of it. The guiding ideal is to avoid any error that might slip in as a result of prejudice or preconception. Later, the authors discussed the falsifi-cationist ideas of Karl Popper in relation to the black ravens: "the observation of a single nonblack raven will falsify the hypothesis that all ravens are black." Huff (2) recently discussed the role of cell proliferation in chemical carcinogene-sis. At one point he discussed the ability of certain putatively nongenotoxic chemicals to induce renal cancer in male rats. The section in question is worth quoting in frill. Meanwhile regulators and administrators should continue to be considerably cautious before embracing a purported mechanism even a reasonable proposed hypothetical mechanism of carcinogenesis-as being pivotal to public health decisions. One example still garnering considerable debate centers on whether chemicals that induce cancers of the tubular cell epitheli-um of the kidney in male rats, concomitant with an increase in cell proliferation and testosterone-mediated ca-2p-globulin protein are relevant or useful to overall hazard identification for humans. The U.S. Environmental Protection Agency (for example) has embraced the concept that these experimental carcinogenic responses are not important to the human situation, whereas others (e.g., the Interational Agency for Research on Cancer) appear properly cautious, or have proposed equally reasonable alternative hypotheses. For example, and yet to be clarified, there are several chemicals known to induce this specific nephropathy syndrome that do not cause kidney cancers, and may or may not produce cancers in other organs; this lack of consistency must be explained. Huff has seen some white ravens, but he has not identified them for other interested parties to study. I too have heard similar rumors, but I have yet to see a convening of the chemical structure, genetic toxicity, hyalin droplet data, and adequate rat cancer bioassay data for such a chemical. Given the importance of the issue under discusion, it would be valuable if Huff were to identify the chemicals to which he referred and present the relevant data for them in a focused paper. This would enable …