Convocation lecture, McMaster U. (Edward Calabrese)

Honorary Doctor of Science Degree Statement

by Edward J. Calabrese, Ph.D. Professor of Toxicology School of Public Health and Health Sciences University of Massachusetts Amherst, MA 01003 Convocation for the School of Nursing and Medical Radiation Sciences Program November 22, 2013 McMaster University Hamilton Ontario I am greatly honored and humbled to accept the Honorary Doctoral Degree from your University. It is an honor that one never truly thinks about because it is far beyond one's normal reach.

I am here today because I am helping to lead a revolution in the biological and biomedical sciences. It is called the Dose-Response Revolution. It is my belief that the scientific and medical communities got the dose response concept wrong many decades ago, concerning how drugs, chemicals and radiation act in the low dose zone, the zone in which we live most of our lives. Throughout much of the 20th century the belief was that the dose response was linear for agents causing cancer and a threshold response for everything else.

My research has seriously challenged these two views. When one challenges the scientific and medical leadership on one of their basic scientific principles you had better be on a solid foundation or you may find yourself delivering pizzas to the students at night rather than correcting their papers.

While I am not here to proclaim that I have convinced the entire scientific and medical communities to my perspective, I can say that I am still correcting student papers at night while eating the pizza rather than doing the delivering.

My story is how do you discover and prove that these scientific and medical leaders made a profound error on a basic principle that has gravely affected our health and economy.

For me it was entirely serendipitous.....much like the discovery of the potato chip or that Rogaine can grow hair. My insights first came as an undergraduate student taking a plant physiology course. In one experiment we were to demonstrate the standard dose response for a synthetic plant growth retardant. However, instead of inhibiting plant growth it stimulated it. The professor asked if anyone was interested in following up on this anomalous finding.....as it turns out I was the only one.

We figured out that the reason the normal experiment did not work was because the wrong dose was used, giving only one tenth of what was prescribed in the directions. When I did the experiment over it revealed this high dose inhibition but also the low dose stimulation. My professor inspired me to repeat this experiment in progressively stronger studies some 11 times, at which point we became convinced that the findings were very reliably reproducible. He then 1

directed me to do an additional two dozen experiments testing closely related aspects of the hypothesis for additional proof of concept.

When all was said and done I knew that I had discovered that a threshold or linear dose response was not operating here but a biphasic one, something I later learned was called hormesis. We published the research in a British botanical journal, I graduated, later getting my Ph.D., became a professor and started a professional life......almost forgetting this earlier intense period of my first research experience.

Nearly two decades later the issue of hormetic-biphasic dose responses became highly visible and provocative with the scientific and regulatory powers proclaiming that it was wrong, could not be reproduced, very trivial at best and was a ploy to undercut environmental regulatory standards.

My long, nearly forgotten undergraduate research experience emerged, telling me that I knew something the others didn't, that such biphasic dose responses could be real and reproducible. I just did not know how general they were, what their dose response characteristics and basic mechanisms were nor how broadly significant their reality could be. The past 20 years have lead me down this path, a path that reconnected me to my undergraduate days. I had taken a long marginalized biological concept, one that never made it into the textbooks, one that was never the subject of a conference, symposium, seminar or even classroom lecture and breathed scientific life into it; we are in the process of changing how the scientific, medical and regulatory communities think and act on this topic.

Such changes in thinking are happening quickly...and at multiple levels within society. We are seeing how numerous medical procedures have incorporated this concept to save, improve and extend lives. It is also affecting how the general public acts as well....as we see new dietary recommendations like the intermittent fast, or the rapid adoption of the 5:2 diet and other developments based on this concept.

All in all, the road has not been easy, as many colleagues and others in the scientific community thought that those challenging the standard protocols of linearity and threshold, while proposing the hormetic alternative, had somehow lost their scientific path.....

My message to you is that big things always start small, with the giant oak from the tiny acorn.....from a professor's observation that his peppermint plants were acting in an odd fashion.

Be curious. Try to figure out the exception to the rule.......you may find something very important and transforming.....However, exploring the exception rather than the rule can also be dangerous to your job health......so it helps to be correct if you go down the lonely path. For in retrospect, I am now very grateful to my old and now deceased professor who made me replicate my experiment so many times and in so many differing ways so that we could have very high confidence in our conclusions...it took me nearly a professional lifetime to appreciate his wisdom and demanding scientific standards, as it undoubtedly preserved my professional life and helped bring me to McMaster University today.

Thank you.

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