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Professor Emeritus John C. Sheehan, whose chemical synthesis of penicillin at MIT in 1957 led to the development of many tailor-made forms of the drug, died Saturday of congestive heart failure at his home in Key Biscayne, Fla. He was 76.
Dr. Sheehan's synthesis of the lifesaving antibiotic opened the way to the development of particular penicillins to combat particular bacteria. He held about 30 patents and among his inventions was Ampicillin, a commonly used semi-synthetic penicillin taken orally rather than by injection.
The synthesis of penicillin solved one of the most baffling problems of modern chemistry. Penicillin-discovered in 1928 by Scottish bacteriologist Alexander Fleming-was desperately needed during World War II, but the natural mold process took months to make a relatively small amount of the miracle drug. During the war, about 1,000 scientists in 39 laboratories in the United States and Great Britain spent about $20 million in a frantic but unsuccessful attempt to synthesize penicillin. After that effort failed, many organic chemists concluded it was impossible.
Eventually, improved fermentation technology led to highly effective procedures for the commercial production of natural penicillin.
Dr. Sheehan, who joined the MIT faculty in 1946, began working on the synthesis of penicillin in 1948. He worked for nine years on the penicillin molecule, aided financially by Bristol Laboratories of Syracuse, N.Y. Medical research was conducted by Merck, Sharp and Dohme Research Laboratories at Rahway, N.J. Dr. Sheehan described the penicillin molecule as unstable. It disintegrates easily, and constructing it in the laboratory, he said, was like "placing an anvil on top of a house of cards."
In achieving total synthesis, Dr. Sheehan also produced an intermediate compound in the form of a basic penicillin nucleus. By stringing various chemicals into the nucleus, he was able to produce new types of pencillin for specific uses. Other researchers built on this work to turn out hundreds of kinds of synthetic penicillin.
Harvard Professor of Chemistry E.J. Corey, a Nobel laureate, paid tribute to his mentor at MIT as "a very conscientious and very effective teacher. He is the undisputed pioneer in the field of penicillin chemistry after World War II. He had a vision and the ability to see important problems and to focus on them." Corey won the Nobel Prize in chemistry in 1990 for the development of the theory and methodology of chemical synthesis, "all of which started with John and his MIT colleagues many years ago," Corey said.
One of Dr. Sheehan's closest MIT colleagues, George H. Buchi, professor of chemistry, emeritus, said that the first total synthesis of a penicillin was made possible by "John Sheehan's brilliant planning and the meticulously high quality of his work." Although it "remains Dr. Sheehan's most significant scientific achievement," he added, it was only one element in an "astonishing career."
Dr. Bucchi paid tribute to the "elegance" of Dr. Sheehan's work in synthesizing penicillin and added, "the knowledge gained in the course of the MIT total synthesis allowed Sheehan, and later on others in the pharmaceutical industry, to prepare medicinally more effective penicillin with side chains different from those available by fermentation."
"These studies also led him to broaden the methodology of amide forming reactions," Professor Buchi said, "and culminated in what was soon termed the `carbodiimide' method in peptide synthesis."
"In addition to these achievements, which were recognized by many honors," he added, "Sheehan tackled successfully a number of difficult structural problems in the area of natural product chemistry."
Professor Sheehan's professional awards include the American Chemical Society (ACS) Award in Pure Chemistry in 1951, and the ACS Award for Creative Work in Pure Chemistry in 1959. In 1964, the City of Philadelphia, crediting him with "saving millions of lives," gave him the John Scott Award and Medal for inventors benefitting mankind.
Born in Battle Creek, Mich., on Sept. 23, 1915, John Clark Sheehan graduated from Battle Creek College in 1937 and received his master's and PhD degrees in organic chemistry from the University of Michigan in 1938 and 1941, respectively. In 1941, he co-developed with the late Professor W.E. Bachmann of the University of Michigan a large-scale method for manufacturing the militarily important high explosive RDX, or cyclonite. He was a senior research chemist at Merck & Co. in Rahway, N.J., from 1941 to 1946.
In 1946, he began a 31-year teaching career at MIT as an assistant professor of chemistry. He was promoted to associate professor in 1949 and to professor of organic chemistry in 1952. He became professor of organic chemistry emeritus and senior lecturer in 1977. Besides his work on penicillin, he also did research in amino acids, peptides, alkaloids, steroids and the synthesis of high explosives. In 1982, MIT Press published his book, The Enchanted Ring: The Untold Story of Penicillin. He was the author of more than 150 scientific publications.
He was a scientific adviser to Presidents John Kennedy and Lyndon Johnson from 1961 through 1965, serving on a number of presidential advisory committees. He served as scientific liaison officer with the American Embassy in London for the Office of Naval Research in 1953-54.
He held honorary doctorates from the University of Notre Dame and Stevens Institute of Technology. He was a Fellow of the Chemical Society/Royal Institute of Chemistry in London, and a member of the National Academy of Sciences, the American Chemical Society, the American Institute of Chemists and the New York Academy of Arts and Sciences.
He is survived by his wife of more than 50 years, the former Marion M. Jennings; a brother, David Sheehan of Battle Creek, Mich; three children, John C. Jr. of Denver, Colo.; David E. of Key Biscayne, and Elizabeth S. Watkins of Saunderstown, R.I., and six grandchildren.
Funeral services were private.
A version of this article appeared in the April 1, 1992 issue of MIT Tech Talk (Volume 36, Number 25).