Disease, the Host Defense, and Q-10

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DISEASE, THE HOST DEFENSE, AND Q-IO JOHN H. HELLER* At this writing there are three Phase I clinical trials of coenzyme Q-IO in terminal metastatic cancer being conducted at three medical centers. Three patients died shortly after the initiation of Q-IO therapy . However, the remaining 10 patients have had their disease stabilized even though they had rapidly growing tumors in which all other therapy had failed. Three of the patients who have been on Q-IO the longest—which is now 6 months—were not expected to live more than but a few weeks after initiation of therapy. They have resumed their normal life and work though tumor is still present. A total of 50 patients will be included in these three Phase I studies. The route to this point in time has been long, expensive, and tortuous . It began some 22 years ago when some experiments, designed to explore whether radiosensitivity of tumors could be increased, were quite successful. The hypothesis which the literature suggested as to why such an effect might be possible (conversion of all anaerobic metabolism to aerobic) was found to be completely erroneous. Thus, the successful results were pleasant to have achieved but confusing as to cause. Naturally, the problem had to be pursued further. Unfortunately , the presumably pure chemical material which produced increased radiosensitivity had, upon chromatographic analysis, 13 different components. The firm that had made it was still under the direction of the Foreign Property Custodian since World War II. * Professor of life sciences, New England Institute Graduate School, Ridgefield, Connecticut 06877. This research, covering so long a period, was sponsored by many foundations , corporations, and individuals. It would be far too long a list to include in toto. However, special mention must be made of some who supported us long and generously. These include the American Cancer Society, the Mary Reynolds Babcock Foundation, the John A. Hartford Foundation, the Heddens-Good Foundation, the Virginia and D. K. Ludwig Foundation, the J. M. McDonald Foundation, the Henry Nias Foundation , the Elsa U. Pardee Foundation, R. J. Reynolds Industries, Incorporated, the Fannie E. Rippel Foundation, the Damon Runyon Memorial Fund for Cancer Research, the Scaife family of Pittsburgh, the Sears Family Foundation, Union Carbide Corporation , the Wallace Genetic Foundation, the Raymond J. Wean Foundation, and the Whitehall Foundation. Perspectives in Biology and Medicine · Winter 1973 | 181 This caretaker management was completely disinterested in science per se and was impatiently waiting resolution of its temporary status. Subsequent batches of purportedly the same material had five, two, and three chromatographic bands, respectively, and were instantly lethal to experimental animals. Painstaking histological examination of the animals originally treated indicated that whatever the effect, direct or indirect, the cells that were crucially involved were the macrophages. This, perforce, led me into the wonderful and confusing world of the reticuloendothelial system (RES). In those days, relatively few investigators were involved in research on the RES and the literature was dispersed in different and often obscure journals. Hence, at the 1954 meetings of the Federation of American Societies for Experimental Biology, in Atlantic City, I posted a sign on the bulletin board suggesting a meeting of those interested in the field. To my surprise, about 25 investigators turned up, and the Reticuloendothelial Society was founded. However, to this day, when the Society is international with its own journal and national branches from Japan to Europe, there is, from my point of view, one major problem. There exists no agreement as to what cellular and/or noncellular elements comprise the RES. Since my interest has not been histological debate but, rather, function, I have for some time used a more catholic phrase—"the host defense system." Under this heading is included almost everything involved in defending the host against alien particles. Thus, this includes macrophages , lyosomes, lyosomal enzymes, lymphocytes, plasma cells, humoral antibodies, cell-bound antibodies, polymorphonuclear leukocytes , monocytes, interferons, etc. Considerable work at this Institute with several colleagues making invaluable contributions has shown that the host defense system is indeed an integrated system. However, the details of this research are too lengthy to be included herein and are published elsewhere [1, 2]. As I mentioned, the aspect...

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