John Robert Veyn
Great BritainBiography of John Robert Vane
Early Life and EducationJohn Robert Vane, a British pharmacologist and Nobel laureate in Physiology or Medicine in 1982, was born as the youngest of three children to Maurice Vane, son of Russian immigrants, and Francesca Florence (Fisher) Vane, daughter of farmers. After receiving his primary education in a state school, John attended King Edward IV School in the outskirts of Birmingham. During the German air raids that began in 1940, the Vane family spent many nights in a bomb shelter in their garden. At the age of 12, John's parents gave him a set of chemical reagents, after which he became passionately interested in chemical experiments. In 1944, he entered the University of Birmingham with the intention of studying chemistry, but his interest in this field soon began to wane. When one of his professors offered him the opportunity to study pharmacology in Oxford with Harold Burn, he, as he later recalled, "seized this opportunity and immediately went to the library to find out what pharmacology was." He considered this decision to be an event that changed his entire career. After receiving a Bachelor of Science degree in 1946 from the University of Birmingham, Vane spent two years as a research fellow in Burn's pharmacology laboratory in Oxford, where he mastered the necessary experimental techniques and principles of biological research. The laboratory method, known as bioassay, allows researchers to determine the biological activity of a substance by measuring its effects in a test system. Burn taught Vane to "never neglect the unusual" in experimental observations and urged him to make pharmacology his life's work. In 1948, Vane completed his training in pharmacological research.
Career and Discoveries
After several months as a research assistant in the Pharmacology Department at the University of Sheffield, Vane returned to Oxford to conduct research for his doctoral degree in the Nuffield Institute for Medical Research. A Storz Fellowship from the Royal Society of London allowed him to complete his work in 1951, and two years later he obtained a Doctor of Philosophy degree. In 1953, Vane moved to New Haven, Connecticut, where he worked as a lecturer and then an associate professor of pharmacology at Yale University until his return to England in 1955. Over the next seven years, Vane was a senior lecturer at the Institute of Basic Medical Sciences at the Royal College of Surgeons. He lectured on pharmacology from 1961 to 1965 and was a professor of experimental pharmacology from 1966 to 1973. During this time, he developed the cascade superfusion bioassay, a method that allows the measurement of the biological effects of multiple substances simultaneously in parallel test systems. Using this method, Vane and his colleagues studied a group of hormone-like natural substances called prostaglandins.
Prostaglandins were first described by gynecologists at the College of Physicians and Surgeons of Columbia University. While performing artificial insemination, they noticed that seminal fluid caused changes in the contractile ability of the uterus. In the late 1930s, Ulf von Euler extracted a substance from ram seminal fluid that had the same effect on uterine contraction. He named this substance prostaglandin, as it was first discovered in the secretions of the prostate gland. Euler preserved these extracts until the end of World War II and in 1945, he handed them over to Sune Bergström of the Karolinska Institute in Sweden for further study. In the late 1950s and early 1960s, Bergström and his colleague Bengt Samuelsson determined the chemical structure of some prostaglandins. In the early 1970s, Samuelsson discovered that prostaglandins are formed in the body from arachidonic acid, an unsaturated fatty acid present in certain types of meat and vegetables. He also found that arachidonic acid and the enzymes that convert it into prostaglandins are present in all eukaryotic (nucleus-containing) animal cells. Different tissues synthesize different prostaglandins, which perform various biological functions. Samuelsson also identified a substance similar to prostaglandins, which he named thromboxane, that differed from the former in molecular structure.
In the 1960s, Vane and his colleagues at the Royal College of Surgeons used the cascade superfusion bioassay to determine the biological activity of certain prostaglandins and thromboxanes and showed that some of them become biologically inactive after passing through the circulation only once. Vane correctly hypothesized that these rapidly inactivated substances are effective only locally, at the site of their release. For this reason, they cannot be considered hormones like cortisol or adrenaline, which circulate in the blood. It was found that these rapidly acting substances, including prostaglandins E and I and thromboxane A2, affect the state of blood vessel lumens. Prostaglandins E, as vasodilators, dilate blood vessels by relaxing the smooth muscle fibers in the vessel walls, thus reducing blood pressure. Prostaglandins I, as vasoconstrictors, cause the contraction of the smooth muscle fibers in the vessel walls, leading to an increase in blood pressure. Thromboxane A2 is a potential vasoconstrictor. While working at the Royal College of Surgeons, Vane discovered in 1971 that aspirin inhibits the formation of prostaglandins and thromboxane A2. Since thromboxane A2 promotes blood clotting, small doses of aspirin can be used to reduce the risk of thrombosis in coronary arteries (blockage of their lumen by blood clots). Vane's research also explained why aspirin is such an effective drug. Although aspirin had been used since the beginning of the century, scientists did not realize that it reduces pain and lowers fever by inhibiting the formation of prostaglandins.
Later Career and Legacy
Appointed Director of Research and Development at the Wellcome Foundation in London in 1973, Vane organized a group to study prostaglandins, led by Salvador Moncada. Moncada planned to conduct research on the tissue of blood vessels, particularly the cells that form their inner layer. The scientists discovered that these cells synthesize a completely different prostaglandin, which they named prostacyclin, or PgI2, which is now known as a subtype of prostaglandin H. They found that thromboxane A2 and prostacyclin have opposite effects on blood clotting and smooth muscle of blood vessels. Thromboxane A2 stimulates clot formation and causes vasoconstriction, while prostacyclin inhibits blood clotting and leads to vasodilation. Prostacyclin is the most potent anticoagulant currently known. Vane and Moncada proposed that thromboxane A2 and prostacyclin form a kind of homeostatic system, thus maintaining opposing forces in balance. Thromboxane A2 accelerates clot formation at sites of vascular injury, while prostacyclin reduces the size of the clot and allows blood circulation to be maintained. The latter is used in various clinical situations, including preventing thrombus formation in devices used to maintain blood circulation during open-heart surgery and protecting the myocardium from damage during angina attacks. Vane shared the Nobel Prize in Physiology or Medicine in 1982 with Bergström and Samuelsson "for their discoveries concerning prostaglandins and related biologically active substances." In his Nobel Lecture, titled "Adventures and Excursions in Bioassay: The Stepping Stones to Prostacyclin," Vane analyzed the research on prostacyclin and its effects on the circulatory system.
The discoveries of the prostacyclin subtype of prostaglandin H and aspirin's ability to block the formation of prostaglandins from arachidonic acid were remarkable progress in the study of prostaglandins. Vane's research opened up new avenues for studying the mechanisms of the development and prevention of angina attacks – the leading cause of death in the United States and other industrialized countries. "In the next two decades," Vane predicted, "we will witness a powerful attack on this process." He claimed that new effective drugs for cardiovascular diseases, bronchial asthma, and even age-related ailments would be found.
Personal Life and Honors
In 1948, Vane married Elizabeth Daphne Page, and they had two daughters together. According to Vane's wife, he was constantly engrossed in his work; for him, "work is life." However, during rare periods of rest, he enjoyed water skiing and underwater swimming in tropical waters.
Vane was an active member of the British Pharmacological Society and the Society for Medicines Research, as well as the American Academy of Arts and Sciences and the American Medical Association. In addition to the Nobel Prize, Vane was awarded the Royal College of Physicians' Bailey Medal (1977), the Albert Lasker Award for Basic Medical Research (1977), the Siba-Ghei-Drew University Prize (1980), and the Dale Medal of the Society for Endocrinology (1981).
