The Copper Sulfate Test: Saving Soldiers from Blood Loss and Speeding Blood Donations

Van Slyke, Donald
Courtesy of the Rockefeller Archive Center

When a person is injured and goes into shock from loss of blood, it is critical to replace this fluid intravenously. But how do doctors know how much fluid to give? During World War II a group of scientists at the Rockefeller Hospital led by Donald D. Van Slyke (1883-1971), and including Vincent P. Dole (1913-2006), devised a simple test for estimating blood volume in shock victims before and after a plasma infusion. The technique was tested clinically by a colleague stationed at the United States Typhus Commission Unit at the Cairo Fever Hospital, in Egypt. During the war, the so-called copper sulfate test saved lives. Others later took advantage of its ability to rapidly estimate hemoglobin in the blood to screen potential blood donors.

The test measures the specific gravity of blood—its density compared to the density of water—by letting a small drop of blood fall into a series of tubes containing standardized solutions of copper sulfate of known specific gravities. Whether the blood drop floats, remains suspended, or sinks gives the doctor information needed to estimate the hemoglobin concentration. By performing analyses before and after a plasma infusion, the patient's blood volume could be quickly determined from a nomogram. This provided information on how much additional plasma was needed. The test had the advantages of being as reliable on a rocking Navy ship as in a safe hospital, and at a range of temperatures. Because of this portability and ease of use, it has been widely used in blood drives to determine whether potential donors have enough hemoglobin to safely give blood. Although more accurate laboratory tests are available, the copper sulfate test remains in use for some purposes today.

Donald D. Van Slyke received his BA and PhD degrees in chemistry at the University of Michigan. In 1907 he joined the Rockefeller Institute as an assistant to chemist Phoebus A.T. Levene. In 1914 Van Slyke was appointed chief chemist of the new Rockefeller Institute Hospital. After his retirement from Rockefeller in 1948, Van Slyke continued his research at the newly established Brookhaven National Laboratory. Van Slyke is remembered as a founder of clinical chemistry. He was elected to the U.S. National Academy of Sciences, and his achievements were recognized with numerous awards and honorary degrees, including the National Medal of Science in 1965.

Dropping blood into a standard copper sulfate solution. From J Biol Chem, 1950, 183: 305-330

Selected Publications

Phillips RA, Dole VP, Emerson K Jr, Hamilton PB, Archibald RM, and Van Slyke DD, with technical assistance from Stanley EG and Plazin J. The copper sulfate method for measuring specific gravities of whole blood and plasma. Biomed Newslett, 1943, 1: 1

Phillips RA, Yeomans A, Dole VP, Farr LE, and Van Slyke DD. Estimation of blood volume from change in blood specific gravity following a plasma infusion. J Clin Invest, 1946, 25:261-269

Phillps RA, Van Slyke DD, Hamilton PB, Dole VP, Emerson K Jr, Archibald RM, and Stanley EG. Measurement of specific gravities of whole blood and plasma by standard copper sulfate solutions. J Biol Chem, 1950, 183: 305-330

Van Slyke DD, Phillips RA, Dole VP, Hamilton PB, Archibald RM, and Plazin J. Calculation of hemoglobin from blood specific gravities. J Biol Chem, 1950, 183: 349-360

Further Reading

Corner GW. A History of the Rockefeller Institute, 1901-1953. New York: Rockefeller Institute Press, 1964

Hastings AB. Donald Dexter Van Slyke (1883-1971): A Biographical Memoir. Washington, DC: National Academy of Sciences, 1976, 48: 307-360

Hastings AB. Donald Dexter Van Slyke. J Biol Chem, 1972, 247: 1635-1640