 By Keyu Liu Featuring P. Roy Vagelos, M.D. “Are you aware that the topics you researched in the past are now integrated into Columbia’s biology course?” Dr. Vagelos smiled. Now in his late 80s, Dr. Vagelos still speaks with passion about his journey as a student in medicine and decades as a researcher and later CEO at Merck, one of the leading biopharmaceutical companies in the world. A short year ago, he donated $250 million to the Columbia Medical School to eliminate the need for student loans and to support our generation’s pursuits in science and medicine. His own pursuit began at around our age. Before Dr. Vagelos’ time as a medical student at Columbia, he spent three years as an undergraduate at the University of Pennsylvania, starting in 1947. Advancements ranged from the molecular understanding of alpha helices and beta-pleated sheets in protein’s secondary structure, to concepts of orbital hybridization and electronegativity, to the first application of quantum mechanics in understanding the hydrogen atom. Amidst these advancements, Dr. Vagelos came to understand the power of scientific knowledge and with that, the possibility to advance technology and to change lives. “What was medical school like? Columbia stress must have not been a problem on your plate.” “I have a terrible memory [for scientific terms], and taking Anatomy was a pain. Thankfully I was able to use chemistry to get me through the first year.” Organic chemistry must not have been a problem on his plate then. After completing his undergraduate education, Dr. Vagelos considered continuing his studies in graduate or medical school. He proceeded to attend Columbia College of Physicians and Surgeons, now Vagelos College of Physicians and Surgeons, in 1950. After four years in medical school, Dr. Vagelos went to Massachusetts General Hospital, where he looked forward to becoming a practicing doctor before he signed up for the Army in 1956. It was during that time when he visited the National Institutes of Health, and was introduced to research. He joined the lab of Dr. Earl Stadtman, who was investigating coenzyme A, the essential kick-starter of the citric acid cycle, which is responsible for the synthesis and metabolism of molecules like fatty acids (Marks 3). Now taught in Introductory Biology I at Columbia, CoA was barely understood during Dr. Vagelos’ time at medical school. Though it was uncommon for a doctor to dedicate his time to research, Dr. Vagelos was immediately drawn to the work on fatty acids, an experience that provided great insights into his future pharmaceutical endeavors. “What would be an incredible moment of your career at Merck?” “When we eradicated a disease.” River blindness is caused by a parasite, Onchocerca volvulus, which is transmitted by the bite of a black fly. These flies breed along rivers, hence the name “River Blindness.” These parasites are prevalent in Sub-Saharan Africa and parts of Latin America and Asia. Microfilaria, the larva of the parasite, can live in the skin, where they cause severe itching, and can also enter the eyes, where they cause inflammation, scarring and eventual blindness. In the mid-1980s, around 10 years after Dr. Vagelos joined Merck, eighteen million people were losing their sight and more than 100 million people were at high risk for this disease. During his years at the NIH, Dr. Vagelos recognized that his strength lies in biochemistry, and decided that his way to cure patients was through drug discovery. His transition to Merck in 1975 marked the beginning of a transformative career. The discovery of ivermectin, the drug that kills the river blindness parasite, was one example. Ivermectin is produced by reducing a double bond in a substance isolated from a fermentation broth, and is found to be the most potent drug with the ability to kill parasites. The chemical structure of the drug increases permeability of the parasite cell membrane, thereby leading to paralysis and apoptosis. When the potential of ivermectin was understood, a Merck research team was sent to West Africa to test its effects. The results were so astonishing that the World Health Organization couldn’t believe its reported effectiveness. The team subsequently undertook a development program with rigorous experimentation as well as a large clinical trial to confirm ivermectin’s power. The trials showed that people could be protected from river blindness by taking a single tablet of ivermectin once a year. The next question was, what should Merck do with such power? Yes, the company might sell the drug and expect great financial prospects, but whom could they sell it to? Those who were most in need of the drug were also among the least capable of purchasing it, and the company was left with a pressing decision to make when the New York Timespublished an article about Merck’s drug discovery. Urgently, the company decided in just two days that Merck would provide ivermectin to anyone anywhere in the world, for as long as it was needed, for free. With the former U.S. President Jimmy Carter’s support, a new World Bank grant was established to support the Mectizan (brand name of ivermectin) Donation Program. The drug contribution began in 1987, and after twenty years, Merck was treating over 90 million patients a year for free. In many regions, the flies became free of parasites, and the disease was on the path of eradication. It is projected that by 2020 the parasite will be completely eliminated in many parts of Latin America and Africa.  “What would be your advice to the younger generation that pursues the field of science or medicine?”
“Pursue the knowledge, not the rewards.” The decade that Dr. Vagelos spent in research was marked by numerous drug developments that transformed millions of lives in and outside of the country. He served as CEO of Merck from 1985 to 1994, during which time the company first introduced the statin family of medicines to treat cardiovascular disease caused by high levels of cholesterol. At the time, drug experimentation was based on studying animal models that mimicked human diseases. Dr. Vagelos instead recognized the potential of targeted drug discovery, with a focus on single molecules rather than an entire organism. He explained, “the key is to understand the exact biochemical mechanism of the disease and then to design a drug that interferes with that molecular mechanism.” His knowledge of biochemistry and his past research experience in fatty acids directed him and his team to an innovative path of drug discovery. This revelation first sparked in Dr. Vagelos’ mind the moment he submitted his application to medical school. But it wasn’t a name on a peer-reviewed paper that he pursued; in fact, he has given many anonymous suggestions to various research scientists in the hope of supporting their experiments (Marks 10). And his learning is nonstop. Dr. Vagelos humorously recounted that when he was nominated to become the CEO of Merck, he had to learn finance and law, but fortunately he could learn from the company’s Chief Financial Officer and General Counsel, who were among the best in their fields. At the end of our interview, Dr. Vagelos said that if there was any essential advice that he would like to impart to our generation, it would be a pure, self-driven passion for the field that we love, unhindered by any other factor and unaffected by superficial rewards. “I have never thought of the gains I would receive from what I do, but rather how I could do more of what I like and do it better.” References: Marks, Andy. “A Conversation with P. Roy Vagelos", Annual Reviews Conversations. 2011. Vagelos, P. Roy. Interview. 7 Dec 2018. Altman, Lawrence K. “New Drug May Curb Tropic “River Blindness”, The New York Times. August 1, 1982. https://www.nytimes.com/1982/08/01/us/new-drug-may-curb-tropic-river-blindness.html Sturchio, Jeffrey L. “Ivermectin: Lessons and Implications for Improving Access to Care and Treatment in Developing Countries,” Community Eye Health. 2001; 14(38): 22–23 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1705916/ Ivermectin https://www.drugs.com/monograph/ivermectin.html Reprint of the New York Times Sunday August 1st, 1982 Issue https://timesmachine.nytimes.com/timesmachine/1982/08/01/issue.html Merck History https://www.merck.com/about/our-history/home.html
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