". . But, but what common property could three diverse anti leukemic drugs have in common?" Logically, they might have none; each could act differently at the cellular level, and each might inhibit a different specific enzyme. Yet, in the clinic, either 6-mercaptopurine, chlorambucil or a folic acid antagonist did cause temporary remissions in certain leukemic patients. And we pondered, in 1954 and early 1955, must there be three individual and totally different explanations for similar clinical findings, or could there be a common thread? Intriguing thoughts . . . perplexing questions.

In 1955, it occurred to me that a common denominator of many anti tumor agents could be their metal binding potentiality. A note to this effect was sent to a well known weekly scientific journal. Seven months later (it seems such an inordinately long time when one waits to hear from a journal editor) the note was rejected. Evidently there was not sufficient documentation. Shortly thereafter, through the kind invitation of Sidney Farber, M.D., I had the opportunity to present these ideas at a seminar at the Children's Cancer Research Foundation. Again, ideas ... no real documentation ... a chelate hypothesis for anticancer activity? . . .

When Doctor I. Newton Kugelmass, Editor of the American Lectures in Living Chemistry, invited a manuscript on the subject, The Chemistry of Chelation in Cancer, I was delighted, for it gave me a chance to tie together the various ideas that I had just presented at a symposium, Metal Binding in Medicine. By now even certain aspects of carcinogenesis seemed best correlated by a metal binding hypothesis. The result is this monograph with over 600 references. "The lady doth protest too much, methinks," yet it is incumbent upon anyone with a different or new hypothesis in the field of cancer to fully document his facts, and above all, to present suggested experiments which will sustain or refute his hypothesis. If the idea has any validity, it should be possible to find or design chelating or metal binding agents which are effective as anti cancer drugs. This has been done! The anti viral agent Kethoxal® was found in our laboratories to be equally as effective as nitrogen mustards against the Ehrlich ascites tumor. The compound was then given to the late B. L. Freedlander, M.D., of Mt. Zion Hospital, San Francisco, for further testing and exploitation. The result is Methyl GAG, now in clinical trial. This may be the forerunner of other useful chelating agents.

In a sense, this book is mainly a compilation of facts about metals and cancer, or metals and their biological function. The question of metals as carcinogenic agents must be faced. Are they in the same category as hydrocarbons and azo dyes? This question is raised in the book. I report every metal that was responsible for the production of a tumor in at least one species. Perhaps the time has come for an international committee to define the term carcinogenesis. A true carcinogen should be active in more than one species, should it not? Thus, some metals should not be ruled "legally" carcinogenic until more experimental work is done.

I am aware that chelation is not the only consideration in these diseases, but it must be considered. While the hypothesis will not explain the phenomenon of resistance, it will correlate many apparently isolated facts. The section, Speculations and Conclusions, was written remembering the admonition of the late J. P. Greenstein, "For some odd reason cancer research has been the graveyard of many a scientific reputation."