Dr. Reidenberg Receives Prestigious

Torald Sollmann Award from ASPET
(American Society for Pharmacology and Experimental Therapeutics)

Currently coined "Personalized Medicine," Dr. Marcus Reidenberg was already researching the field -- defining it as "Individualized Medicine"-as early as the 1960s. He directed a course for the American College of Physicians (1973) and prepared a book on the topic for The Medical Clinics of North America (1974). A pioneer in many areas of clinical pharmacology, Dr. Reidenberg has been honored with the prestigious Torald Sollmann Award. "It's a great time to be a pharmacologist," he says.

Dr. Torald Sollmann, who wrote the Manual of Pharmacology and played a dominant role in establishing pharmacology as a specialized field of medicine, believed that the future of pharmacology “depended on imaginative persons dedicated to hard work and self-development.” With more than 50 years as a physician-scientist who has continually pressed the boundaries of discovery, Dr. Reidenberg embodies the full meaning of the Torald Sollmann Award (ASPET). A Professor of Pharmacology, Medicine, and Public Health, as well as Assistant Dean, his research has consistently furthered advancements in pharmacology that have directly benefited patients in the clinical setting.

By 1972, Dr. Reidenberg assessed: “It was clear that the clinical pharmacologists working in the area of individual differences in drug response had learned enough about the causes of these variations to make this information known to the practicing community.” After directing a course for the American College of Physicians (ACP) on the topic, he prepared The Medical Clinics of North America book on “Individualization of Drug Therapy.” In 1982, he directed another course for the ACP and prepared a second Medical Clinics of North America book, this time on “Clinical Pharmacology of Symptom Control,” helping to make symptomatic therapy more acceptable to the medical profession.

He had not only conceptualized “Individualized Medicine,” Dr. Reidenberg was driving a number of other advancements. In the 1960s, investigators of adverse drug reactions counted any symptom in patients taking a drug as an adverse reaction to the drug. By the late 1960s, Dr. Reidenberg had conducted a survey of 414 people who were not taking any medications in order to acquire data on any symptoms they may have exhibited. They had many. “We concluded that proper controls are just as important in studying adverse drug effects as in studying beneficial ones,” explains Dr. Reidenberg. Because patients with poor renal function had more adverse drug effects than metabolically normal people, Dr. Reidenberg began a research program in which he studied drug metabolism in uremia, and subsequently wrote a book, Renal Function and Drug Reaction (Saunders, 1971), that showed impaired renal function changes the dose-response relationships of drugs. It was also determined that “age” was an important independent variable affecting dose-response, which has since influenced the care of the elderly.

It all starts with a question that doesn’t have an answer…

“Why do we do all this research in clinical pharmacology?” asks Dr. Reidenberg. “The whole purpose of this work is to make the response to a drug more predictable. If the response is more predictable, then we can use the drug in a way that will increase both its safety and its effectiveness. The individualization of drug therapy, now called personalized medicine, is to try to make the response more predictable. We can tailor the choice and dose of a drug depending on how well we understand an individual’s state - how best can we predict their response.”

When treating patients, Dr. Reidenberg would sometimes encounter a question that did not have an answer. “It all started with a question regarding one of my patients where I couldn’t look up an answer. But I had to find out. More recently, some questions come up that relate to whole groups of patients. Before the technology boom, you did the best you could to get additional scientific methodologies. Use what you have, and if you haven’t got it, then you try to invent something. That’s what all of us have done as scientists. Instead of taking a night in the library to answer the question, maybe it took two years. But the question was worth answering.”

Personalized medicine is working on the individualization of therapy (choice of drug and best dose to use) using a patient’s genetics. “When I was starting out, genes were something in peas researched in an Austrian monastery. Before the explosion of knowledge in genetics, we were looking at disease interactions-- liver disease, kidney disease and different rates of drug metabolism and how to address it. We dealt with more or less, more of a drug or less of it. But today, because of advancements in genetics, we’re looking at an all or nothing response. We’re seeing that a particular gene or mutation, when present, can give either an all or nothing response - either you respond to a drug, or not. We first started to understand this all or nothing response with respect to bacterial resistance. We saw certain changes in bacteria (in response to a drug) in those people who were receiving an antibiotic that selected for bacteria genetically resistant to the antibiotic. The antibiotic had to be changed to treat the infection that did not respond to the first drug.”

Dr. Reidenberg’s latest question: What can happen “after” a drug is discontinued? When he receives the Torald Sollmann Award medal from ASPET, he will deliver a talk on this topic and has written a paper to be published in one of the ASPET journals. One of the examples he will use is a study of patients admitted to the hospital for Acute Coronary Syndromes. Some of these patients were on statins prior to admission, some were not. People entering the hospital, in whom statins were stopped, have a greater mortality than those people who were never on statins - obviously indicating a serious consequence when statins are discontinued in such a scenario. “Laboratory data shows that in the days, or week, after you stop the statins, the body responds in a way that one would anticipate might increase the frequency of cardiac events,” says Dr. Reidenberg. “We talk about withdrawal for opioids or barbiturates, but if it’s not a mood affecting drug, we tend to neglect withdrawal reactions. Today, the science has advanced enough that we have both laboratory and clinical ways to assess if there are these withdrawal responses - either biochemically in the lab or by seeing what happens to patients in the clinical trials for the week or two after the drug was stopped and the trial was over.”

A Full Professional Life Involves Public Service

Working with the World Health Organization, the FDA, and as an appointee to the Joint Commission on Prescription Drug Use, Dr. Reidenberg has played a leading role in the public arena. The thalidomide tragedy had led to the formation of the Commission on Prescription Drug Use; serving as its Vice Chair, Dr. Reidenberg helped to identify the types of information about drugs that could not be obtained experimentally, showed how good observational techniques could yield valuable information, and solidified drug epidemiology as an accepted discipline.

Asked what public responsibilities does a physician-scientist have, Dr. Reidenberg explains: “I certainly feel that one has the responsibilities that a citizen has, so that to me, a full professional life has been teaching, patient care, research, and public service. My neighbors are as qualified to be on the local school board as I am. They’re not as qualified to work with WHO on the essential drug project. For the amount of time I’m prepared to donate to public service, I want it to be where I can be the most effective and where there is this particular area where I have something that most other people don’t have - that is the background with medicine and pharmacology. I prefer to devote my time to public service in that activity. To me, just all part of a full professional life.”

An Assistant Dean, and Professor of Pharmacology, Medicine, and Public Health, Marcus M. Reidenberg, MD, joined Weill Cornell in 1975. He majored in botany at Cornell University, received his MD from Temple University, and was a postdoctoral fellow in pharmacology at Temple and in general practice while in the U.S. Navy. He has served as an advisor to the NIH and FDA and has held leadership positions with ASPET, IUPHAR, and ASCPT. He has served on seven WHO Expert Committees, chairing two of them, and was a WHO advisor to the Ministry of Health of the People’s Republic of China (1993). Dr. Reidenberg is Editor Emeritus of Clinical Pharmacology and Therapeutics and received the American Society for Clinical Pharmacology and Therapeutics Oscar B. Hunter Memorial Award in Therapeutics in 2008.

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