A Day at CHORI (Children’s Hospital of Oakland Research Institute)

As a hematology fellow at the Scripps Clinic in the 1980s, my friend and colleague Sheldon Hendler, MD, PHD, recommended that I read an article in Science magazine. The manuscript entitled “Cancer and Diet,” by Bruce Ames, PhD, described the mutagens and carcinogens to which we are exposed on a daily basis that are found in a normal diet. His paper then examined the defenses that we have developed as a species.

Dr. Ames has distinguished himself as a pioneer in the study of aging, degenerative disease and cancer and I have read many of his papers since then. You can imagine my delight when I received a phone call some months ago and found that my interlocutor was none other than Bruce Ames, inviting me to speak at his research institute.

On Tuesday, January 31, I traveled to Oakland to present a symposium. Dr. Ames arranged for me to meet many of his colleagues. The topics ranged from neuraminic acid residues expressed as neoantigens on dividing cancer cells, to antifungal agents as anti-cancer drugs. One discussion of particular interest surrounded sphingomyelin metabolism as an important mediator of tumor cell progression. A subject about which I knew little prior to this discussion but will certainly now examine with interest.

It is my hope that I might forge collaborations with some of these investigators. But, there is little that could have prepared me for the pleasure I experienced when sitting across the table from Dr. Ames, while sipping a freshly brewed espresso (deftly prepared by Dr. Ames himself), while we discussed Bruce’s six decades of extraordinary discoveries. Everywhere I looked was an award or a textbook that he had authored. Despite his many accomplishments he was humble, engaging and very witty.

My symposium that afternoon introduced the attendees to human tumor primary culture studies as predictors of response to cancer therapy. I then moved through the accumulated data supporting the clinical outcomes and finally examined our developmental work, finishing with our published collaboration with investigators at NYU and Cornell on the study of a novel class of Wnt inhibitors. Lively discussion ensued.

Among the attendees was Bengt Mannervik, who asked several good questions. I note his presence for he is one of the leading experts in the field of glutathione metabolism and a scientist who I had met several times before. As one of the fathers of glutathione s-transferase chemistry, Bengt’s work had influenced my earlier studies. It was an unexpected honor to have him in the audience, as a visiting professor on sabbatical from Uppsala.

As I have noted before, the reception from the scientists in these fora improves as they examine the data on its own merit, unaffected by the clinical dogma and politicking that contaminates so much discourse in medical oncology today. There was no agenda, just scientific interest and open discussion. It was a refreshing departure and a welcome opportunity to interact with open-minded investigators.

In the audience was Dr. Ames’ wife, Giovanna, a former professor of biochemistry at Berkeley, and a scientist whose work included the earliest discovery of the ABC transporters, now recognized as the basis for the human p-glycoprotein drug resistance mechanisms. At the end of the lecture, Giovanna Ames, impressed by the data, raised her hand and asked, “If what you need is a small portion of each patient’s tumor to conduct these studies, what do we have to do to be sure that every doctor sends you a piece of tumor?” While I’m not sure I that have the answer to her question, I am very sure that I like the way she thinks.