Heidelberger, Michael

(b. 29 April 1888 in New York City; d. 25 June 1991 in New York City), chemist who is generally considered to be the father of immunochemistry.

Heidelberger was the son of David Heidelberger, a merchant and salesman, and Fanny Campe, a homemaker. The Heidelbergers had lost a child before the birth of Michael, who was followed by a brother two years later. Heidelberger’s education was obtained entirely in New York City. After graduating from a public elementary school, he attended the Ethical Culture High School. He then obtained his B.S. (1908), A.M. (1909), and Ph.D. (1911) degrees in chemistry from Columbia University.

Through Samuel Meltzer, the family’s physician and a staff member at the Rockefeller Institute for Medical Research, Heidelberger met Rockefeller biochemists Phoebus A. Levene, Walter Jacobs, and Donald D. Van Slyke. They advised him to go abroad for a postdoctoral year to extend his training, recommending the laboratory of Richard Will-stätter in Zurich, Switzerland. After his year with Willstät-ter, Heidelberger accepted a position as an assistant to Jacobs at the Rockefeller Institute in 1912.

At first Jacobs and Heidelberger carried out chemother-apeutic research on polio, but without success. They next turned to African sleeping sickness, which was caused by a microorganism known as a trypanosome. Other investigators had shown that some organic arsenic compounds were effective against trypanosomes, but these chemicals had serious toxic side effects. The Rockefeller chemists synthesized new arsenicals in an effort to find one that was a safer, more effective therapeutic agent. A compound that they called Tryparsamide was shown in clinical trials to be superior to any of the previously used drugs against sleeping sickness. The Belgian government, grateful for a drug that successfully treated a disease that was a serious problem in its African colonies, awarded the Order of Leopold II to Jacobs, Heidelberger, and their coworkers.

With a war on in Europe, Heidelberger enrolled in an officer’s training course in the summer of 1915. At about this time he also met Nina Tachau, whom he married in June 1916. The couple had one child, a son Charles, who went on to become a noted oncologist. After the United States entered the war in 1917 Heidelberger served as a first lieutenant in the Army Sanitary Corps, and was assigned to the Rockefeller Institute, much of which had been given over to training army physicians in laboratory techniques.

After the war Jacobs and Heidelberger continued their chemotherapeutic research, this time focusing on bacterial infections. Their efforts yielded little in the way of practical results, and the two chemists soon turned to other projects. Heidelberger went to work with Van Slyke, who was chemist to the hospital of the Rockefeller Institute. One of Hei-delberger’s duties was to prepare the oxyhemoglobin needed for Van Slyke’s study of the equilibrium between oxygen and hemoglobin. During the course of this work, which involved keeping the materials at low temperature, Heidelberger designed the first refrigerated centrifuge.

During the two years that Heidelberger worked with Van Slyke he received his introduction to immunology through collaboration with the noted immunologist Karl Landsteiner in research on the immunological properties of hemoglobin. Oswald Avery, microbiologist of the pneumonia team at the institute, asked for Heidelberger’s chemical assistance on the “soluble specific substance” of the pneumococcus bacillus, which seemed to hold the key to the immunological response of the blood to the microorganism. The more that Heidelberger purified the substance, the less nitrogen it contained, which was surprising because at the time, all immunologically active substances were thought to be proteins. The Rockefeller group was soon able to demonstrate that the capsular substance of the pneumococcus, which provoked the immunological response, was a carbohydrate, not a protein. These studies established that polysaccharides played a crucial role in immunology and opened a field of research that was to occupy Heidelberger for many years.

In 1927 Heidelberger accepted the post of chemist at Mount Sinai Hospital. The following year he moved to Columbia University as an associate professor of medicine (changed to biochemistry in 1929) and as chemist at Columbia Presbyterian Hospital. Heidelberger and his colleagues at Columbia provided the first solid evidence of the chemical nature of antibodies, unequivocally demonstrating that antibodies were proteins, namely gamma globulins. They also developed quantitative analytical micromethods for studying the antibody-antigen reaction.

During World War II Heidelberger became involved in an attempt to find a way to protect and cure animals infected with anthrax and to study the toxic principle of the castor bean. Based on an experiment involving student volunteers, Heidelberger recommended to the army that some 8,500 men at a training camp for aviators in South Dakota be vaccinated with pneumococcal polysaccharides in an effort to immunize them against pneumonia, with an equal number receiving saline solution as a control. Within two weeks there were no more new cases of pneumonia of the types vaccinated against in the immunized group, but an average of one new case a week in the control group from weeks three through sixteen.

After World War II Heidelberger suffered a personal loss with the death of his wife Nina from cancer in 1946. She had been active in the cause for world peace, and Heidelberger became more involved in this effort himself after her death. His research interests became focused principally on the relations between chemical constitution and immuno-logical specificity. In 1948 his title was changed from professor of biochemistry, the position he had held since 1945, to professor of immunochemistry.

In 1955, a year before he was to reach the mandatory retirement age at Columbia, Heidelberger accepted an invitation from Selman Waksman to be a visiting professor of immunochemistry in Waksman’s Institute of Microbiology at Rutgers University. Columbia gave him a year’s terminal leave with pay so that he would not have to resign, and made him emeritus professor of immunochemistry in 1956. In that same year he married his second wife, Charlotte Rosen, who shared his love of music. Heidelberger was an excellent clarinet player, and Charlotte was an accomplished violist and violinist.

Heidelberger left Rutgers in 1964 to become an adjunct professor of pathology at the New York University School of Medicine. He continued to work in the laboratory on immunochemistry until close to the time of his death, following a stroke, at the age of 103. He is buried in New York.

Heidelberger’s work played a crucial role in the development of immunochemistry. He demonstrated that carbohydrates could serve as antigens to provoke immune responses, and provided the first chemical insight into antibodies by showing that they were proteins. His contributions to science and medicine were recognized through fifteen honorary degrees and forty-six medals, citations, and awards, including the National Medal of Science in 1967 and the prestigious Albert Lasker Award twice, in 1952 and 1978.

An extensive collection of Heidelberger’s personal papers resides in the History of Medicine Division of the National Library of Medicine, Bethesda, Maryland. Heidelberger published his “Reminiscences” in three parts in Immunological Reviews: 81 (1984): 7-19; 82 (1984): 7-27; and 83 (1985): 5-22. Useful sources of biographical information are Elvin A. Kabat, “Michael Heidelberger, April 29, 1888-June 25, 1991,” Journal of Immunology 148, no. 1 (1992): 301-307, and M. Stacey, “Michael Heidelberger, 29 April 1888-25 June 1991,” in Biographical Memoirs of Fellows of the Royal Society 39 (1994): 179-197. An obituary is in the New York Times (27 June 1991). An oral history interview with Heidelberger is at the History of Medicine Division of the National Library of Medicine.

John Parascandola