Salvador E. Moncada
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Salvador E. Moncada - Self-Presentation Sir Salvador Moncada I was born on 3 December 1944 in Tegucigalpa, Honduras, from a Honduran father of Spanish descent and a Jewish mother born in Romania in Chernowitz, now known as Chernivsty and located in Ukraine. Her family escaped Europe in 1938-39 and, following a series of unexpected events, settled in Honduras. Hers was a German speaking family which continued to speak mainly German for the rest of their lives. A number of her relatives were persecuted and disappeared during the war. My mother was a housewife and my father, although trained as a medical doctor, never practiced medicine and became a businessman. My family moved from Honduras to El Salvador in 1948 where I lived for the next twenty-two years. I grew up in a happy household. My father was Latin American from a Catholic family and my mother an Eastern European Jew. Neither of them was religious but they possessed defined cultural stereotypes. This created a rich environment, often contradictory, but always respectful and provided me with a wide perspective on things. I developed an early interest in biology and medicine and remember collecting insects and devising ways of keeping them in captivity to observe them. I would also, when they died, dissect them to see their internal organs. This was at about the age of eight or nine. By the time I was eleven I was determined to study medicine and to do research as the only career option in my life. I also developed, from very early on, an awareness of injustice, which I could see all around me. This led to early political activism and denunciation of the ills of the society I belonged to. I have been married twice, in 1966, in El Salvador, to Dorys Lemus Valiente, a biochemist. We had two children: Claudia Regina born in1966, now a medical doctor in general practice, mother of two and living in London, and Salvador Ernesto, born 1972 and deceased in 1982. In 1998 I married Princess Esmeralda de Belgique. We have two children, Alexandra Leopoldine born 1998 and Leopoldo Daniel born in 2001. From 1951-56 I attended the Colegio Bautista in San Salvador. It was a high quality primary school in our neighbourhood and the Director at the time was Evalena McCutcheon, a North American who had lived in El Salvador for many years. She was an excellent teacher and a significant influence on our lives. From 1957-61 I attended the Instituto Nacional “General Francisco Menéndez”, which had previously been a military academy and provided a high standard of education as well as strict discipline. I was sent to this school, attended by children from working class and poor families, because my father thought it important for me to understand the living conditions of people in the country. From 1962-70 I studied medicine at the Facultad de Medicina, Universidad de El Salvador. At that time it was one of the best medical schools in Central and South America, since it had recently been updated and restructured along the lines of modern medical schools in the USA. This was carried out by a group of distinguished Salvadoran doctors who had previously trained in the US and other places. Chief among them was María Isabel Rodríguez, a Salvadoran cardiologist of high scientific and clinical repute, who became my mentor. The medical school had a programme of visiting scientists, through which I met Augusto Campos, a Peruvian pharmacologist who had trained in the US working on the pharmacology of the sympathetic system. He provided my introduction into pharmacology and to medical research. When I started medical school, my particular interest was in science and I intended to combine research with medical practice. During my clinical years, however, working in the various hospitals I was deeply disturbed by the poverty of the majority of the population of El Salvador and realised that their medical needs could only be addressed by structural changes in society leading to improvements in public health. As a result of this I became politicised and interested in training in Epidemiology and Public Health. Politics in El Salvador at that time was of a militant nature and by June 1970, immediately after I graduated, I was captured by the secret police, beaten up and expelled from El Salvador into Honduras. All this happened shortly after the border war between EI Salvador and Honduras, which created animosity between the people of the two countries. In Honduras, I started to work in the Department of Physiology in the University of Honduras, accepting the only job available in the Faculty of Medicine. This marked my return to basic medical sciences, my original interest. - 1 - My wife and child were not allowed to join me there as they were Salvadoran so we were obliged to meet when we could in Guatemala, the country in between. In order to keep my family together I realised that I had to go abroad. A Guatemalan doctor – Fernando Molina – had spent some time in the UK at the Royal College of Surgeons where he had met John Vane. Molina suggested that we write to John to see if he could give us some advice about post-graduate education in the UK. John replied, inviting me to come to work in his laboratory based on the recommendation of Molina. I arrived in London on 19 February 1971. John Vane was a Professor in the Department of Pharmacology in the Institute of Basic Medical Sciences at the Royal college of Surgeons. The environment in the department was highly interactive and intellectually stimulating with many distinguished British and foreign scientists working there. I was lucky because at the time of my arrival the hypothesis about the potential mechanism of action of aspirin and other non-steroidal anti-inflammatory drugs was being discussed. I was invited to join the project and set to work on a series of successful experiments that a few months later formed part of a landmark trio of publications in the journal Nature. Those papers explained the mechanism of action of these drugs and also their main side effect of gastric damage. The result was that I found the work in the laboratory so exciting and consuming that I never thought to go back to the practice of clinical medicine. This is something that I do not regret, although I have always felt that my research has been guided by my medical knowledge that gives me an integrated vision of physiology and pathophysiology. Between July 1974 and July 1975 I went back to Honduras, where I set up a laboratory at the Medical School. However, the conditions in the country were not conducive to research and therefore the following year I returned to the UK at the invitation of John Vane to lead a research group at the Wellcome Research Laboratories in Beckenham, Kent. John had become overall R&D Director of the Wellcome Foundation. By then I had become interested in platelets and their role in vascular disease. This was a significant and very productive change of direction since, within a year, we had discovered an enzyme in platelets that generated thromboxane A2, a powerful vasoconstrictor and platelet-aggregating substance and shortly afterwards, in the vascular wall, we discovered prostacyclin, a vasodilator with potent anti-platelet aggregating properties. Since the platelets and the vessel wall generate substances with opposing biological properties I thought that this was a balancing system in the vasculature of pro- and anti-thrombotic tendencies. This hypothesis is now widely confirmed. The fact that the generation of thromboxane A2 is inhibited by very small concentrations of aspirin, without affecting the generation of prostacyclin in the vessels, has led to the widespread use of small doses of aspirin for the prevention and treatment of cardiovascular disease and as a result, millions of people currently benefit from those discoveries. Furthermore, the “balance hypothesis” has explained, more recently, the cardiovascular side effects of the anti-inflammatory agents called COX2 inhibitors, which preferentially inhibit the generation of prostacyclin in the vasculature. I remained at Wellcome for the next twenty years, occupying different positions, first as leader of the Prostaglandin Research Group, then head of the Department of Prostaglandin Research until 1985, when I became Director of Therapeutic Research and finally, in 1987, Director of Research (UK). In 1984 I became interested in endothelium-derived relaxing factor (EDRF) discovered by Furchgott a few years earlier and began a project which led us to its identification as nitric oxide (NO). We also elucidated the pathway to its biosynthesis from the amino acid L-arginine and revealed many of the biological actions. Our findings led me to propose that the “L-arginine: NO pathway” is a widespread transduction mechanism for regulating cell function and communication. This turned out to be the case following the finding of nitric oxide in the peripheral and central nervous system as well as in other systems including the immunological system. The implications of the discovery of this novel mediator continue to be explored, but it is clear that it has represented a significant advance in our biological knowledge and that it is providing clues for the prevention and treatment of disease. I worked at the Wellcome Research Laboratories until 1995. In my tenure as Research Director I directed and oversaw the discovery and development of a number of useful medicines including lamotrigine (anti-epileptic), zomig (anti-migraine), atovaquone (anti-malarial) and the initiation of the project that led to the anti cancer compound, lapatinib. The market pressures on the drug industry were being increasingly felt at Wellcome, which not only was owned by the Wellcome Trust, the only shareholder, but was a highly academic institution successfully combining discovery research with research for drug discovery.