- What is your job title and affiliation?
Retired Chairman and Chief Executive Officer, Merck & Co., Inc.
- Briefly tell us about your educational and career background.
University of Pennsylvania, BA in 1950, Major in Chemistry
Columbia University, College of Physicians and Surgeons, MD in 1954
Massachusetts General Hospital, Residency 1954-56
National Institutes of Health, Cardiology and Biochemical Research, 1956-66
Washington University School of Medicine, Chairman, Dept of Biochemistry, 1966-75
Merck & Co., Inc., President Merck Research Laboratories, 1975-85
Merck & Co., Inc., Chairman and CEO, 1985-94
- What are your Board certifications?
No Board certifications
- With which professional societies/organizations (e.g. AACC) are you involved?
National Academy of Sciences, American Philosophical Society, American Society of Arts and Sciences, American Society of Biochemistry and Molecular Biology
- Just for fun, tell us a few interesting facts about yourself:
Wife, four children and eight grandchildren
- Favorite activities/hobbies
Tennis, jogging, ocean swimming and cooking
- Favorite places you have traveled
- Favorite book/movie
"Team of Rivals" by Doris Kearns Goodwin
- Most fun/adventurous thing you’ve ever done
Canoeing in the Ozarks
- What area(s) do you specialize in?
Biochemistry, enzymology and drug discovery
- What initiated your interest in this (these) area(s) and how did you eventually choose this (these) area(s) for your career?
I became interested in chemistry while I was in high school, listening to excited chemists discuss their work at Merck while I was working in a family-run luncheonette in Rahway, New Jersey. After majoring in chemistry at Penn, I continued this interest subversively while in medical school and medical residency. Then while I did cardiology at NIH, I worked part-time with Dr. Earl Stadtman who taught me biochemistry. Earl was one of the best biochemists at NIH and he was a wonderful teacher – very patient and very generous of his time. He convinced me to remain at NIH beyond the two years that were required of me to fulfill my doctor draft requirements. I stayed for a total of ten years. During this period, I did biochemistry and enzymology research.
- What are your clinical and research interests?
My research interests started in fatty acid metabolism in microorganisms. Along with my co-workers, we determined the biosynthesis of fatty acids. We then studied metabolism of complex lipids and finally worked on cholesterol.
My clinical interests were internal medicine and cardiology, but I largely moved into bench research early in my career.
- What, in your opinion, has been the most important contribution you have made to the field of laboratory medicine?
My most important contributions are two types: In basic biochemistry, the discovery of Acyl Carrier Protein and its involvement in the biosynthesis of fatty acids. In drug discovery, I led the Merck Research Laboratories that discovered the first statins, lovastatin and simvastatin, which were used to reduce high blood cholesterol levels and ultimately revolutionized the treatment of coronary heart disease. Another drug, finasteride, was discovered for relief of benign prostate enlargement and was later shown to reduce the incidence of prostate cancer when used prophylactically.
- Are there specific aspects of practicing laboratory medicine that you find unappealing?
Drug discovery is my favorite aspect of laboratory medicine.
- What were some of the most rewarding and/or challenging moments of your career?
The discovery of Acyl Carrier Protein (ACP) and its characterization and studies in fatty acid metabolism were thrilling experiences in my early years.
As leader of Merck Research laboratories I had many challenging experiences but I will discuss only a few. First, during our work on the statins, clinical research done on the first statin discovered in the world, Compactin, was stopped in Japan (Sankyo Company) without explanation. Both Compactin and lovastatin targeted the enzyme, HmG CoA reductase. Rumor from Japan indicated that Compactin caused cancer in animals, but the Japanese laboratory would not release information which they regarded as industry secret. All clinical work was stopped at Merck on lovastatin for about two years while animal cancer studies were completed. With assurance that lovastatin was not carcinogenic it was returned to clinical studies which demonstrated safe reduction of total cholesterol and low density lipoprotein cholesterol. Lovastatin was approved by the FDA and was the first statin marketed in the world.
Another challenging experience came during the development of the hepatitis B vaccine. The first vaccine developed at Merck was derived from the surface antigen of the virus isolated from plasma of intravenous drug users and gay males who were carriers of hepatitis B virus. Although this vaccine was shown to be safe and effective in large clinical studies, shortly after its launch in 1981, AIDS was identified as a new syndrome with unknown eliology among intravenous drug users and gay males. Since the vaccine was made from a substance derived from the blood of people who were at high risk for AIDS, there was concern that the vaccine might be contaminated with the agent (not yet identified) that caused AIDS. Fortunately, several years prior to that we had started collaboration between the Merck Research team and Dr. William Rutter of UCSF and Dr. Ben Hall of the University of Washington. The researchers put the gene that codes for the hepatitis B surface antigen into baker's yeast which was then able to express the surface antigen. This protein was shown to be fully antigenic and protective in human clinical tests. Thus, Merck Research Laboratories developed the first recombinant vaccine in the world after what initially appeared to be a lost cause.
- How would you recommend achieving an optimal work/life balance?
Achieving optimal work/life balance requires having an understanding and supportive wife. Best balance for me starts with an hour of exercise in the mornings to clear the head and get the body moving. Tennis is sacred on weekends. I like to work part of every day. How much of the day? That is largely determined by availability of other interesting activities or people.
- What excites you about practicing laboratory medicine everyday?
My excitement comes from drug discovery. Since I had to retire from Merck when I was 65 in 1994, I have been Chairman of two small biotech companies – Regeneron in Tarrytown, New York, and Theravance in South San Francisco, California. Through close contacts with scientists in these two companies, I continue my interests in drug discovery.
- What are your predictions for advances in laboratory medicine and/or your area over the next ten years?
My prediction is that drug discovery will be largely dependent on understanding of functional genomics. We need to understand which genes are turned on or off in all diseases. With knowledge of specific gene involvement, the gene products which are proteins can be targeted for drug discovery. Both macromolecules (monoclonal antibodies, cytokine traps) and small molecules will be aimed at diseases that currently are important unmet medical needs such as cancer and Alzheimer's disease. In addition, better drugs will be discovered for diseases that now have treatments that are not optimal – depression, Parkinson's, schizophrenia, diabetes, arthritis, etc.
- What do you see as the challenges facing young scientists in laboratory medicine?
Challenges facing young scientists are largely linked to availability of funds to do research. NIH funding, which has been essential for research support over the last 60 years, has begun to shrink under the Bush administration. Hopefully this will change under Obama.
- What specific goals would you recommend that young scientists in your discipline set for themselves? Any suggestions on how to achieve them?
Young scientists should strive to have excellent understanding of their scientific discipline, keep up with all current literature in their field and keep alert as to what is going on in other scientific disciplines that can make a contribution in their own work. Remember that interdisciplinary research is required for solving most biological questions; so know what is going on around you. As for how to assure this, be in a place with other exciting scientists.
- Describe how you have been able to give back or contribute to the organizations and the profession in general through your involvement in AACC.
I give back to the profession by participating in committees and task forces largely at the National Academy of Sciences. I also spend time advising students at Columbia University Medical Center.
- How did you get started in these organizations and what advice do you have for young people wanting to get involved?
I get involved in these organizations through my work in biochemistry and volunteering to work on committees.
- Do you have any other specific comments or advice that you like to provide to the members of SYCL?
Yes, AACC is your professional organization that needs your participation at all levels, so please make time and become actively involved – it will enrich your career many fold! I applaud AACC’s efforts to nurture and develop young clinical chemists and the SYCL program is terrific. It makes me proud to be a member of AACC.