Earl Wilbur Sutherland Jr. was born on November 19, 1915, in Burlingame, Kansas. He was an American scientist who studied how medicines and chemicals in the body work. In 1971, he won a Nobel Prize in Physiology or Medicine for discovering how hormones, such as epinephrine, affect the body. His research showed that hormones use special chemical signals called second messengers, like cyclic adenosine monophosphate, or cyclic AMP, to carry out their effects. He passed away on March 9, 1974.

Early life and education

Sutherland was born on November 19, 1915, in Burlingame, Kansas. He was the second youngest of six siblings and was raised by his mother, Edith M. Hartshorn, and his father, Earl W. Sutherland. His father, originally from Wisconsin, attended Grinnell College for two years but later lived a life focused on farming. He moved to New Mexico and Oklahoma before settling in Burlingame to start a family. His mother, from Missouri, received some training in nursing at a school for women. To support the family, Sutherland’s father owned a dry goods store, where he gave each child a job. Sutherland began fishing at age five, and this activity remained a lifelong interest.

As a high school student, Sutherland participated in and performed well in several sports, including tennis, basketball, and football.

In 1933, at age 17, Sutherland began studying for a Bachelor of Science degree at Washburn College in Topeka, Kansas. To afford his education, he worked as a medical staff assistant at a local hospital during his undergraduate years. He graduated in 1937, at age 21. He then attended Washington University School of Medicine in St. Louis, where he formed a close relationship with Carl Ferdinand Cori. In 1942, Sutherland earned a Doctor of Medicine degree.

Career

In 1940, while studying at the Washington University School of Medicine, Sutherland first worked in research as an assistant in pharmacology in the laboratory of Carl Ferdinand Cori. Cori later won a Nobel Prize in Physiology or Medicine in 1947 for discovering how glycogen is broken down in the body. Under Cori’s guidance, Sutherland studied how the hormones epinephrine and glucagon affect the breakdown of glycogen into glucose. In 1942, he worked as an intern at Barnes-Jewish Hospital in St. Louis.

After earning his medical degree from Washington University in 1942, Sutherland served as a doctor in the U.S. Army during World War II. He returned to Washington University in St. Louis in 1945 and continued research in Cori’s laboratory. Sutherland credits his mentor, Cori, for helping him choose a research career instead of becoming a practicing doctor.

During his time at Washington University School of Medicine, Sutherland held several teaching roles, including instructor in pharmacology (1945–46), instructor in biochemistry (1946–50), assistant professor in biochemistry (1950–52), and associate professor in biochemistry (1952–53).

In 1953, Sutherland moved to Cleveland to work as a professor of pharmacology and chairman of the pharmacology department at Case Western Reserve University’s School of Medicine. There, he collaborated with Theodore W. Rall, who became a lifelong research partner. Together, they studied how hormones work at the molecular level. During his ten years at Case Western Reserve University, Sutherland made important discoveries that led to the identification of cyclic adenosine monophosphate (cyclic AMP) and its role as a secondary messenger.

In 1963, Sutherland became a professor of anatomy at Vanderbilt University School of Medicine in Nashville. This position allowed him to focus more on research. He continued his work on cyclic AMP, receiving financial support from the American Heart Association in 1967. He held his teaching role at Vanderbilt University until 1973.

In 1973, after ten years at Vanderbilt University, Sutherland moved to Miami and joined the faculty at the University of Miami’s Miller School of Medicine as a distinguished professor of biochemistry. He continued researching adenosine monophosphate and guanosine monophosphate, co-authoring four papers in 1973 alone.

While working in Cori’s laboratory, Sutherland, with help from colleagues, made discoveries about glycogen metabolism that later led to his identification of cyclic AMP’s biological activity. Cori’s laboratory had already established the basic mechanism of glycogen metabolism, for which they were awarded the Nobel Prize in Physiology or Medicine. Sutherland helped identify the importance of liver phosphorylase (LP) in glycogenolysis. He found that LP was rate-limiting, meaning glycogen metabolism depends on this enzyme. LP became the focus of his research for several years, and his most famous discovery came from experiments on LP and hormone interactions.

After identifying LP’s importance, Sutherland moved to Western Reserve University, where he worked with Ted Rall, Walter D. Wosilait, and Jacques Berthet. Together, they published a series of papers in the Journal of Biological Chemistry titled The Relationship of Epinephrine and Glucagon to Liver Phosphorylase, released in four parts. These papers described the purification of LP and its properties. Researchers found that LP’s activity depends on adding or removing a phosphate group, a process called phosphorylation. Later experiments showed that epinephrine and glucagon increase phosphate uptake in liver slices, suggesting these hormones activate LP. A later paper in the series indicated that this activation was caused by phosphorylase kinase. The series also studied how LP is inactivated and characterized an enzyme initially called LP-inactivating enzyme, later renamed liver phosphorylase phosphatase. These papers also analyzed LP’s molecular weight and other factors. Researchers found that LP activation increased with the addition of 5-AMP, a precursor of cAMP, though this was not known at the time.

The fourth paper in the series, The Relationship of Epinephrine and Glucagon to Liver Phosphorylase: IV Effect of Epinephrine and Glucagon on the Reactivation of Phosphorylase in Liver Homogenates, was published in 1956. In this paper, Sutherland and his colleagues studied epinephrine and glucagon using liver cell homogenates instead of intact cells. This was the first time a hormone pathway was studied using a homogenate. They observed similar effects in liver homogenates as in whole liver slices. Importantly, they observed the response in two stages. The first stage involved a particulate fraction producing an unknown heat-stable factor in the presence of epinephrine and glucagon. This factor then stimulated the formation of liver phosphorylase in a different fraction of the homogenate where hormones were not present. This unknown factor, later named cyclic AMP, was crucial to the discovery of secondary messengers.

Although the discovery of cyclic AMP and the concept of second messengers were significant, Sutherland’s findings were achieved through trial and error. Initially, Sutherland and Ted Rall believed a sucrose homogenate was necessary to keep liver cells healthy, based on Rall’s experience with mitochondria. However, they later found that sucrose was not needed, and removing it improved results. Sutherland also initially believed intact cells were essential for hormonal effects. After Rall convinced him to use liver homogenates, they observed a nearly doubled rate of LP activation, proving intact cells were not always necessary. Finally, Sutherland ignored Jacques Berthet’s request to use the Lehninger Hard Pour technique, which involved carefully decanting supernatant material. Berthet had insisted on this step, but Sutherland proceeded without it.

Personal life

Sutherland married Mildred Rice in 1937, the same year he graduated from Washburn College. In 1944, during World War II, Sutherland was asked to serve as a surgeon in a military unit under General George S. Patton. He was later sent to Germany, where he worked as a doctor in a military hospital until 1945. Sutherland and Mildred Rice had two sons and a daughter.

In 1962, Sutherland divorced Mildred Rice. The next year, when he became a professor of physiology at Vanderbilt University, Sutherland married Claudia Sebeste Smith, who was the assistant dean at the university. Sutherland and Claudia Smith remained married for the rest of his life.

Awards and achievements

• 1937 – Received a Bachelor of Science degree from Washburn College in Topeka, Kansas;
• 1942 – Earned a Doctor of Medicine degree from Washington University School of Medicine in St. Louis, Missouri;
• 1969 – Received the Torald Sollman Award in Pharmacology and the Gairdner Foundation International Award;
• 1970 – Won the Albert Lasker Award for Basic Medical Research;
• 1971 – Received the Nobel Prize in Physiology or Medicine and the Achievement Award from the American Heart Association;
• 1971 – Honored with the Golden Plate Award from the American Academy of Achievement;
• 1973 – Awarded the National Medal of Science by Richard Nixon.

In 1952, Sutherland was given the Banting Memorial Lectureship. In 1953, he became Chairman of the Case Western Reserve University Department of Pharmacology in Cleveland, Ohio. In 1967, he was named a Career Investigator by the American Heart Association. In 1973, he was elected as a member of the National Academy of Sciences.

Sutherland was a member of several scientific societies, including the American Society of Biological Chemists, the American Chemical Society, the American Society for Pharmacology and Experimental Therapeutics, the American Association for the Advancement of Science, and Sigma Xi. From 1951 to 1956, he was a member of the editorial board for the Biochemical Preparations Journal. From 1957 to 1958, the editorial board of the Journal of Pharmacology and Experimental Therapeutics sought is attention.

Death

On March 9, 1974, Sutherland died from internal bleeding caused by surgical problems after a major esophageal hemorrhage. He was 58 years old.

Legacy

After Sutherland passed away in 1974, the Miller School of Medicine created the Sutherland Memorial Lecture. In 1976, Vanderbilt University started the Sutherland Prize, which is given each year to a faculty member who has received national or international recognition and respect. The winner receives $5,000, and their name is engraved on a silver bowl. In 1997, Vanderbilt honored Sutherland by starting a Sutherland lecture. In 2001, the university created the Sutherland Chair of Pharmacology. Heidi E. Hamm, a Vanderbilt faculty member, was appointed to this position when it was created and still holds this title today.