Ting-Chao Chou

Ting-Chao Chou (born 1938 in Taiwan, Chinese name: 周廷潮) is a Chinese American theoretical biologist, pharmacologist, cancer researcher and inventor. His 353 scientific papers have been cited in 40,108 times in over 1,469 biomedical journals as of October 15, 2022. He derived the median-effect equation (MEE) from the physico-chemical principle of the mass-action law, and introduced the median-effect plot in 1976. With Paul Talalay of the Johns Hopkins University School of Medicine, he derived the combination index equation (CIE) for multiple drug effect interactions, and introduced the concept of combination index (CI) for quantitative definition of synergism (CI<1), additive effect (CI=1), and antagonism (CI>1) using computerized simulations. This article has received 7,731 citations internationally in a broad spectrum of journals. Since all terms of MEE and CIE are dimensionless relativity ratio thus generally applicable regardless in vitro, in animals and in clinical trials, or physical states, resulting in econo-green bioresearch and new drug evaluation and bio-development. This integrated theory and algorithms allow conducting small number of dose-data points, conservation of laboratory animals and reducing the number of patients in clinical trials. Consequently, this allows saving time and cost and resources as well as increasing efficiency and cost-effectiveness in medical, pharmaceutical research and new drug development with automated computer simulation. With colleagues, T.C. Chou is inventor/co-inventor of 40 U.S. Patents, mainly for anticancer agents. He was induced to Johns Hopkins Society of Scholars in 2019.

T.C. Chou's 353 publications are listed in Web of Science. The peer reviewed articles have been cited 40,108 scientific papers published in over 1,469 bio-medical journals as of October 14, 2022. Mr. Chou has a H-index of 75 and i10-index of 285.

The CI theorem is developed for drugs (or effector entities) regardless of mechanism of actions, and regardless of dynamic orders and or the units of each drug in the combination. The method has been applied in the combination of anti-cancer drugs, anti-HIV agents, drug-radiation, and traditional Chinese herbal medicines. On March 16, 2016 the publisher/global website, Elsevier had a news release indicated "Chou & Talalay paper from 1984 makes history".

In 1972 he joined the Laboratory of Pharmacology at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City as an Assistant Professor, affiliated to Cornell University Graduate School of Medical Sciences. He became a Member and Professor in 1988. After 40 years of service at MSKCC, he retired on June 1, 2013 from the Directorship of Preclinical Pharmacology Core Laboratory, Molecular Pharmacology & Chemistry Program of MSKCC, and established the PD Science LLC in 2013 in Paramus, New Jersey, to promote MAL based biodynamics, pharmacodynamics, combination index, and bioinformatics [MAL-BD/PD/CI/BI] theory and application.

The algorithms of the median-effect equation and the combination index theorem of the physico-chemical principle of the mass-action law and their computer simulation offer the new interpretation/illustration of the ancient Chinese philosophy. This revelation of correspondence and complementarity have been presented or published at the following major national or international philosophical congress, conference, forum, or symposium: (i) American Philosophical Association East Annual Meeting, Baltimore, MD 12/28/2007; (ii) World Congress of Philosophy, Seoul, Korea 8/3/2008; (iii) Peking University School of Life Science and Department of Philosophy, Beijing, China 10/24/2008; (iv) 16th International Conference of Chinese Philosophy sponsored by International Society of Chinese Philosophy, Taipei, Taiwan 7/8-15/2009; (v) 13th Yijing World Congress, Wuxi, China 6/14/2010; (vi) 7th International Forum on the Development of Traditional Chinese Medicine, Tianjin, China 9/21-23/2011; (vii) Bio-IT World Europe Bio Informatics 2011, Hanover, Germany 10/11-13/2011.

Taking the advantage of facile CI determination, a new simple graphic representation of three or more drug combinations has been introduced by T.C. Chou and J. Chou in 1998. This method allows visual inspection of two-to-n drug combinations in the same circular frame which can be used to project the plausible semi-quantitative projection of what would happen at the higher numbers of drug combinations, form the low numbers of drug combinations. Using heavy red solid lines representing strong synergism and heavy blue broken lines representing strong antagonism, and thinner solid or broken lines for weaker interactions, a grading system can be established. It is easy to obtain the overall perspectives for planning the cocktail design of multiple drug combinations. The polygonogram graphics for five anticancer drugs with different mechanism of actions has been featured on the front-cover of May 2011 issue of Integrative Biology, published by the Royal Society of Chemistry, Cambridge UK.

The combination index (CI) concept was introduced by Chou T.C. and Talalay P. in 1984. The derived combination index equation for two drugs is:

The idea of isobologram, i.e. the equi-effective curve at various concentrations or doses of two drugs, has been around for a century. However, only until 1984 the formal derivation of its equation in the general form was introduced by Chou and Talalay. The isobol equation is just a special case of the CI equation. Thus automated computerized construction of either the classic isobologram (at constant ratio combinations) or the normalized isobologram (at non-constant ratio combination) can be performed in seconds using CompuSyn software. In addition, the isobol method is now amendable for three or more drug combinations. Both Fa-CI plot and isobologram yield identical conclusion of synergism or antagonism. The Fa-CI plot is effect-oriented whereas isobol is dose-oriented. Both graphics can be considered two-sides of the same coin. However, Fa-CI plot is visually more convenient to use than isobologram since data point over crowding in isobologram at various effect levels can be avoided.

The median-effect equation (MEE) of the mass-action law (MAL) was delivered by Chou in 1976 through the derivation of over 300 rate equations of enzyme dynamics, patten analysis, combination analysis, followed by mathematical induction and deduction.

Also introduced by Chou in 1976 was the median-effect plot which is a plot of log (D) vs log [(fa)/(1-fa)] or log [(fa)/(fu)] yields a straight line with slope (m) and the x-intercept of log (Dm), where Dm equals to the anti-log of the x-intercept. This unique theory holds true for all dose-effect curves that follows the physico-chemical principle of the mass-action law, for all entities regardless of the first-order or higher-order dynamics, and regardless of unit or mechanism of actions. MEE is derived by system analysis using enzyme kinetics and mathematical inductions and deductions where hundreds of mechanism specific individual equations are reduced to a single general equation. Both left and right sides of the MEE are dimensionless relativity ratio. When the m and Dm are determined, the full dose-effect curve is defined. Since the median-effect plot yields straight lines, the theoretical minimum of only two data points allow the drawing of the full dose-effect curve. This fundamental revelation defies the common held belief that two data points cannot draw a defined does-effect curve, since MAL algorithm adds two default points: does zero and Dm as the universal reference point. The main significance of MEE is the mediation that "Dose" and "Effect" or "Mass" and "Function" are interchangeable. The unified general MAL theory-based "top-down" approach [MAL-BD/PD/CI/BI] is opposite and yet the complimentary alternative to the traditional specific observations/statistics-based "bottom-up" approach for scientific research and development.

Chou was born in Changgangling Village, Hukou Township, Hsinchu County, Taiwan on September 9, 1938 to Chao-Yun Chou and Sheng-Mei Chen.

Under Japan's rule of Taiwan 1895-1945, the Chou family established a private family school teaching Chinese characters and classics. His father was the teacher. After his father died, the widowed mother sent him to Hsin-Chu Normal School affiliated primary school with three-hour round-trip daily commute in the sixth grade. After the Taiwan Provincial Hsinchu High School, he entered Kaohsiung Medical University majoring in pharmaceutical sciences where he graduated summa cum laude. He was accepted by the Pharmacological Institute of National Taiwan University College of Medicine and received the master's degree under the mentorship of Chen-Yuan Lee, Director of the Institute, and Dean of the Medical School. In 1965, he received a full scholarship from Yale University where he devoted to the mathematical aspects of quantitative biology. He received a Ph.D. degree with high honors. He did a postdoctoral fellowship at the Johns Hopkins University School of Medicine under Chairman of the Pharmacology Department, Paul Talalay, during 1970-1972.