ABSTRACT

Whelan J. ( Jack) Hayes, one of our most illustrious colleagues, lamented in his book the lack of accepted theories of toxicology.

He compared and contrasted toxicology with physics, which has many theories amenable to exceptionally accurate testing. On the other hand, toxicology has ancient (50-yr-old-or-more) protocols, which were designed at a time when the volume of knowledge on toxicology was but a small fraction of the current level. The novel informational content of standard protocols, be it acute, subchronic, chronic, developmental, reproductive, or, for that matter, inhalation studies, has long ago been exhausted for any type of theoretical consideration. Kinetics is routinely ignored in study design, and even though the asserted goal of toxicologic studies is to characterize the dynamics of toxic effects, it is done in a haphazard, cookbook fashion that is completely unsuitable for epistemology. Not surprisingly, statistics plays a very important role in analyzing experimental data that are largely uninterpretable. The fundamental characteristic of any scientific discipline is to conduct hypothesis testing and thereby accumulate a critical volume of knowledge that an emerging theory then simplifies and makes available to others in a greatly abbreviated manner. Toxicology is still in the developmental stage of hypothesis testing, with the focus of research moving from biochemistry to cell biology to molecular biology to genetics and back in the hope of finding the “magic bullet” — the solutions to contradictory and, to a large extent, uninterpretable data provided by standard protocols. This may not happen. If not for a theory, or at least partial theories, forcing a radical rethinking of the standard protocols, there will be no tangible progress in this fascinating discipline, which, in our view, perhaps holds the key to understanding the molecular basis of life.