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special/viewpoint: Jonathan Rees Complex Disease and the New Clinical Sciences Science 2002; 296: 698-700 [Abstract] [Full text] [PDF]

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Mechanistic vs Direct Methods of Clinical Investigation

Phillip H Abbosh   (16 May 2002)

Mechanistic vs Direct Methods of Clinical Investigation 16 May 2002
Phillip H Abbosh, MD/PHD student Indiana University Respond to this E-Letter: Re: Mechanistic vs Direct Methods of Clinical Investigation	While Johnathan Rees' viewpoint "Complex Disease and the New Clinical Sciences" [April 26, p 698] was intriguing and at times justified, his discussion of the usefulness of basic and translational research is partly unfair. That there is a clog in the pipeline of advances in clinical medicine is unquestionable (1), but the first successes in the "bench-to- bedside" approach have been overlooked by Rees. The well publicized drugs Gleevec, ONYX-015, and Herceptin are prime examples of the mechanistic approach, and it is well known that many more are on the way (2). Therefore, mechanistic studies are not so futile as Rees would have the reader believe. Rees neglects to mention that the observation-to-treatment method fails just as the mechanistic approach has. For example, interest in using nitrogen mustards as cancer chemotherapy was initiated during the World Wars. It was observed that tissues most effected by these weapons had high proliferative activities, and so the movement began (3). At the time of the first clinical trial for neoplasms, evidence that mustards were genotoxic was only beginning to be demonstrated in Drosophila (3, 4). The failure of DNA damaging agents is well-documented in the containment of neoplastic diseases (5). One wonders how cancer treatment would have evolved had there been mechanistic insight at that time into molecular pathways governing apoptosis, DNA repair, and the cell cycle. It may be that a synthesis of both the mechanistic approach and the method Rees describes will be most fruitful in clinical advancement. Certainly both are at work in the field of cancer research. For instance, decreased risk of death from colorectal cancer by taking NSAIDs is well documented, but the exact mechanism is still being actively researched to improve the effect. Truly, there is a great need for improvement in the quality and quantity of patient oriented researchers. Hopefully, disease-oriented researchers and ‘true’ clinical investigators can work more closely towards a combined approach at clinical research. Phillip H. Abbosh Indiana University School of Medicine Department of Integrative and Cellular Physiology Bloomington, IN 47405 1. D.G. Nathan. JAMA. 280, 1427 (1998). 2. J.B. Gibbs. Science 287, 1969 (2000) 3. A. Gilman and F.S. Philips. Science 103, 409 (1946). 4. National Defense Research Committee. Chemical warfare agents, and related chemical problems. (Summary technical report of Division 9, NRDC). Washington, D.C.: [s.n.] 1946. (DTIC AD234249). 5. B.A Chabner, C.J. Allegra, G.A. Curt, P. Calabresi, In Goodman and Gilman’s the Pharmacological Basis of Therapeutics, J.G. Hardman, A.G. Gilman, L.E. Limbird, Eds. (McGraw-Hill, New York, 1996), pp 1233-1287.