Earl Wilbur Sutherland, Jr.

56

Earl Wilbur Sutherland, Jr. : biography

November 19, 1915 – March 9, 1974

The fourth paper published in this series, entitled “The Relationship of Epinephrine and Glucagon to Liver Phosphorylase: IV Effect of Epinephrine and Glucagon on the Reactivation of Phosphorylase in Liver Homogenates”, came out in 1956 and was the most influential and groundbreaking of those released. In this paper, Sutherland and associates furthered their investigation of epinephrine and glucagon. The key to the success of this experiment was the use a homogenate of liver cells rather than intact liver cells, as they had been doing in their previous experiments. The general consensus among researchers at that time was that the study of hormones was only possible using intact cells; this was the first instance that a hormone pathway was studied using a cell homogenate. Sutherland and his co-authors were able to observe similar effects in liver homogenate to what was observed in whole liver slices. More importantly, they were able to observe this response in two stages. This stage response was characterized by the particulate fraction producing an unknown heat stable factor in the presence of the hormones epinephrine and glucagon. This factor then stimulates the formation of liver phosphorylase in a fraction of the homogenate where the hormones are not present. This unknown heat stable factor, which was produced in the presence of hormones and ultimately led to the secondary formation of liver phosphorylase, was later termed cyclic AMP.Butcher, R.W.; Robison, G.A.; Sutherland, E.W (February 1968). “Some Aspects of the Biological Role of Adenosine 3’,5’-monophosphate (Cyclic AMP)”. Circulation 37: 279-306.Robison, G.A.; Sutherland, E.W (1969). “The role of cyclic AMP in the control of carbohydrate metabolism”. Diabetes 18: 797-819.

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.Sutherland, Earl W (16 November 1970). “On the Biological Role of Cyclic AMP”. The Journal of the American Medical Association 214: 1281-1288. 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

Sutherland married Mildred Rice in 1937, the same year that he graduated from Washburn College. In 1944, during World War II, Sutherland was called into service as a battalion surgeon under General George S. Patton, and was later was sent to Germany, where he served as a staff physician in a military hospital until 1945."Earl W. Sutherland, Jr. – Biography." Louis Calder Memorial Library. Web. 24 November 2011. . He had two sons and a daughter with Mildred Rice.