Academia and research In 1940, while studying at the
Washington University School of Medicine, Sutherland had his first encounter with research as an assistant in
pharmacology in the laboratory of Carl Ferdinand Cori, who won a
Nobel Prize in Physiology or Medicine in 1947 for his discovery of the mechanism of
glycogen metabolism. Under Cori's guidance, Sutherland conducted research on the effects of the hormones
epinephrine and
glucagon on the breakdown of glycogen to glucose. After receiving his medical degree from Washington University in 1942, Sutherland served as a
World War II army physician. He returned to
Washington University in St. Louis in 1945, where he continued to do research in Cori's Laboratory. Sutherland accredits his decision to pursue a research career, as opposed to entering the medical profession, to his mentor Cori.
Discovery of cyclic AMP While working in Cori's laboratory, Sutherland, with the help of his co-workers, made several discoveries concerning the mechanism of
glycogen metabolism that, years later, led him to his discovery of the biological activity of cyclic AMP. Cori's laboratory had previously established the basic mechanism of glycogen metabolism, for which they were awarded the
Nobel Prize in Physiology or Medicine. These four papers document the purification of LP and the analysis of several of its properties. First, it was determined that the enzymatic activity of LP depends on the addition or removal of a
phosphate group, a process called
phosphorylation. Even though the discovery of cyclic AMP and the idea of
second messengers were of great importance to the world of medicine, Sutherland's findings were actually achieved through strenuous trial and error. First of all, Sutherland and Ted Rall were convinced that a
sucrose homogenate of liver cells was absolutely necessary in order to keep their cells healthy and proliferating. This inference was made by Rall from his experience studying
mitochondria, which responded well to these sucrose homogenates; however, it had nothing to do with what was being studied at the time. It turned out that this sucrose was not necessary for the homogenate and once they set up the experiment without sucrose they were able to see more effective results. Secondly, Sutherland initially believed that there was something vital about the intact cell, and that disrupting its structure would not produce any hormonal effect. However, after some debate, Rall had convinced Sutherland to use liver homogenates. Once they had witnessed nearly a doubling of the rate of LP activation, they knew this belief in that keeping cells intact was crucial to studying the effects of hormones was not necessarily true, at least in this case. Finally, Sutherland had decided to ignore Jacques Berthet's request to conduct the same experiment using proper lab technique, specifically the Lehninger Hard Pour, where the supernatant material was decanted by pouring the liquid into another test tube once the particulate fraction reached the top of the original tube. Berthet not only demanded this step of the procedure be done through careful aspiration, he also critiqued the lack of specificity during centrifugation with respect to suspension height, rpm and time. The willingness of Sutherland and his associates to modify their experimental procedures and mistaken assumptions allowed them to make the discoveries that they made. ==Personal life==