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2008年10月23日,美国斯隆-凯特林癌症研究中心(Memorial Sloan Kettering Cancer Center)临床前实验室主任周廷潮教授来所访问并做学术讲座,周教授在耶鲁大学获药理学博士,曾任康奈尔大学药理学系教授。讲座题目为:The Fundamental Issues in Biomedical Research -- from the Perspective of Contemporary Status,雷晓光博士主持讲座。

发布时间:2008/10/23

Summary:

The unified theory of dose and effect, as indicated by the median-effect equation for single and multiple entities and for the first and higher order kinetic/dynamic, is derived based on the physical/chemical principle of the mass-action law (Chou, T.C., J. Theor. Biol. 59: 253-276, 1976; Pharmacological Rev. 58: 621-681, 2006). Rearrangements of the median-effect equation (MEE) lead to the Michaelis-Menten, Hill, Scatchard, and Henderson-Hasselbalch equations. The “median” serves as the universal reference point and the “common link” for the relationship of all entities, and all kinetic/dynamic orders. The “median” provides a mass-action law based GPS (UPS) concept for quantitative bio-informatics as indicated in Nature Precedings

[http://precedings.nature.com/documents/2064/version/2] on 07/22/08.

Over 300 mechanism-specific equations have been derived and published using the mathematical induction-deduction process. It is proven that “dose” and “effect” are interchangeable. The median-effect principle (MEP) leads to the fundamental conceptual proclamation that we can draw a “specific curve” from only two data points if they are determined accurately. This theory provides algorithms for computerized simulation of dose and effect that allows reduced experimental size, experimental costs and minimized use of laboratory animals.

It is argued, although learning from Nature’s “entities” and “properties” are very important for knowledge building, it is even more important to understand Nature’s basic “principle” and “law”. Based on MEP/MEE, the following “fundamental issues” have been raised: i) What is the additive effect of two drugs? (Especially for the fact that drug combinations have been used worldwide in therapy of cancer and AIDS); ii) What is synergy? (There are over 20 definitions for “synergism” in biomedical literature and the controversies have lasted for over a century. Without a clear “definition of synergy”, how can scientific communities settle, and governmental agencies regulate, the “synergy claims”?); iii) How to draw a dose-effect curve? (For centuries, the “empirical” random curve fitting have been used, but is there any theoretical basis in it?); iv) How to assess low-dose risk of carcinogens, toxic substances and radiation? v) How to calculate Ki from IC50 in a simple system? vi) How MEP can be applied to have efficient and effective drug discovery? vii) Is the contemporary peer review system and practice sound and fair? Or lopsided? Most of the above important issues can be solved by the mathematically derived median-effect principle of the mass-action law.