Max Tishler

• Born: October 30, 1906
• Birthplace: Boston, Massachusetts
• Died: March 18, 1989
• Place of death: Middletown, Connecticut

American chemist

Tishler led research teams that synthesized ascorbic acid (vitamin C), cortisone, riboflavin, pyridoxin, pantothenic acid, nicotinamide, methionine, threonine, and tryptophan. He led a microbiological group that developed fermentation processes for actinomycin D, vitamin B₁₂, penicillin, and streptomycin. He also invented sulfaquinoxaline to treat coccidiosis.

Primary field: Chemistry

Primary inventions: Synthetic vitamins; sulfaquinoxaline

Early Life

Max Tishler was born in Boston, Massachusetts, the fifth of six children of Samuel and Anna Tishler, Jewish immigrants from Romania and Germany, respectively. Samuel abandoned the family when Max was four or five years old, and from an early age everyone had to work. Max and his younger sister were the only ones to graduate from high school, and he was the only one to attend college. Max worked in a drugstore until he completed graduate school (Boston English High School) and earned enough to support himself, pay his tuition, and help his mother and younger sister.

Tishler attended Tufts College (now Tufts University) with a $400 annual fellowship and, during his senior year, with a teaching assistantship. First an English major, he later became a chemistry major. Although one professor advised him not to do so because of prejudice against Jewish chemists, another encouraged him to enter the field to help break down the current barriers. In 1928, he received his B.S. degree in chemistry and became a licensed pharmacist.

Beginning in 1930, Tishler attended Harvard University with a $1,000 annual teaching assistantship. He received his M.A. and Ph.D. degrees in 1933 and 1934, respectively. On June 17, 1934, he married Elizabeth M. Verveer, who had been a student in his freshman chemistry laboratory at Tufts. The couple had two sons, Peter Verveer Tishler (b. 1937), a physician and genetics researcher, and Carl Lewis Tishler (b. 1947), a clinical psychologist.

Tishler stayed at Harvard as research associate (1934-1937) and instructor (1936-1937). Since no academic position was available, in 1937 he became a research chemist at Merck and Company in Rahway, New Jersey, then known only as a producer of reagent chemicals, where he was put in charge of developmental research.

Life’s Work

In the late 1930’s, George Merck, Jr., the president of Merck and Company, decided that, because no other American firm was working on vitamin research, his company should enter the field. Tishler’s first assignment, the first of his numerous successes, was to develop a synthesis of )>riboflavin (vitamin B₂) different from that already patented in 1934. He simplified the procedure and increased the yield. His large-scale, economical method permitted riboflavin to be used to enrich white bread.

Tishler’s next task, a new synthesis for the sulfa drug sulfapyrazine, which the cheaper penicillin had rendered uneconomical, resulted in an important spin-off. Sulfaquinoxaline, which Tishler discovered with John Weijlard in 1942, was added to chicken feed and dramatically reduced the incidence of coccidiosis (a parasitic disease of the intestinal tract caused by microscopic organisms called coccidia), which had previously killed as much as half of the flocks. Its application not only made available disease-free, nutritious, cheap food but also encouraged the search for new drugs for the poultry industry.

Although Lewis H. Sarrett had synthesized the anti-inflammatory, steroidal hormone cortisone in 1948, the yield was very low. Tishler and his team reduced the number of steps required from forty to twenty-six and greatly increased the yield. According to Sarrett, Tishler “transformed complicated organic synthesis from an esoteric intellectual exercise in the laboratory to useful products of great public value.…He created the paradigm of pharmaceutical research and development which has been followed by his successors throughout the industry ever since.”

Tishler’s research on cortisone, hydrocortisone, and dihydrostreptomycin brought him Merck’s Board of Directors’ Scientific Award in 1951. In what Tishler himself called “a golden age as far as medicinal chemistry is concerned,” his teams developed commercial syntheses for pantothenic acid (vitamin B₃), biocytin vitamins, alpha-tocopherol (vitamin E), indomethacin (a nonsteroidal, anti-inflammatory drug), nicotinic acid (niacin), chlorothiazide, amitriptylene, aminopyrazine, aminoquinoxaline, alpha-methyldopa, and the amino acids threonine and tryptophan. His team with Robert Denkewalter and Ralph Hirschmann developed the first total synthesis of the enzyme ribonuclease. His work with Selman A. Waksman on the antibiotic streptomycin helped empty sanatoriums of patients suffering from tuberculosis, and he collaborated with Louis F. Fieser of Harvard University on a large-scale synthesis of phylloquinone (vitamin K) and a study of its relationship between its structure and biological activity.

Tishler met once a week with each of his research teams to discuss their progress. He was the author of more than 130 articles and the holder of more than one hundred patents on chemicals, vitamins, drugs, and hormones. To quote Sarrett again, “He taught me how to be human, to get a lot out of people by being warm with them.…I learned more from Max Tishler about research in the pharmaceutical industry than from any other man.” According to Tishler’s wife, “Max’s vocation and avocation was chemistry.”

Tishler advanced through the Merck hierarchy rapidly. From research chemist (1937-1941) he became section head in charge of process development (1941-1944), director of development research (1944-1953), vice president and executive director of scientific activities (1954-1956), president of Merck, Sharpe, and Dohme Research Laboratories (1956-1969), member of the board of directors (1962-1970), and senior vice president of research and development (1969-1970).

As he approached his mandatory retirement age of sixty-five, Tishler was asked to become head of the Weizmann Institute in Rehovot, Israel, but he declined the offer. He soon received offers from no less than nine universities. In 1970, he began his second career by joining the faculty of Middletown, Connecticut, which had recently begun its graduate program in chemistry. He continued his research on biologically active compounds with his students until a few weeks before his death. He served as professor of chemistry (1970-1974), university professor of the sciences (1972-1974), chairman of the Department of Chemistry (1973-1974), and from 1975 until 1989 as professor of chemistry emeritus and university professor of the sciences emeritus.

A lifelong smoker, Tishler ceased smoking in the hope that this would relieve his emphysema. This unpretentious and friendly scientist who had spent his whole life using chemistry to fight various diseases and who had served as mentor and role model to generations of both industrial and academic chemists succumbed to this disease at the age of eighty-two.

Impact

A great believer in team research, Tishler transformed complex organic synthesis from an intellectual laboratory exercise to the production of useful products of significant value to the public. On Tishler’s death, F. Roy Vagelos, Merck’s chairman and chief executive officer, described him as “an example of scientific integrity, and an inspiration of research achievement, for whole generations of scientists both in industry and academia.…The lives of countless patients around the world were benefited by drugs resulting from his pioneering in developmental research, and the science of chemistry was enriched.” In introducing Tishler at his election to the National Inventors Hall of Fame for his large-scale syntheses of riboflavin and sulfaquinoxaline, on February 6, 1982, Lewis H. Sarrett stated, “You might say Dr. Tishler invented the term ’developmental research.’”

Tishler received many awards and honors: election to the U.S. National Academy of Sciences (1953), the Chemical Industry Award (1963), the American Institute of Chemists’ Chemical Pioneer Award (1968) and Gold Medal (1977), the Eli Whitney Award for Inventions (1973), and the Sloan-Kettering Institute for Cancer Research’s Chester Stock Award. In the American Chemical Society, he was chairman of the Division of Organic Chemistry (1951), society president (1972), and recipient of the Priestley Medal, the society’s highest award. President Ronald Reagan awarded him the National Medal of Science in 1987 as “a giant on the chemical scene these past fifty years.”

Bibliography

Fisher, Steve. “The Inventors: Inventing Better Health.” Science Digest, May, 1983, 16, 17, 102. An illustrated article describing how Tishler’s work has influenced millions of lives through his achievements in the pharmaceutical industry in general and the syntheses of riboflavin and sulfa drugs in particular.

Kauffman, George B. “Max Tishler: Pioneer.” Chemtech 20, no. 5 (May, 1990): 268-274. Recalls his life and achievements, with an emphasis on his work at Merck and his postretirement years at Wesleyan University.

Sarrett, Lewis, and Clyde Roche. “Max Tishler: October 30, 1906-March 18, 1989.” Biographical Memoirs 66 (1995): 352-369. This brief biography published by the National Academy of Sciences details Tishler’s life and career and includes a formal portrait and selected bibliography of his publications from 1935 to 1965.

Seymour, Raymond B., and Charles H. Fisher. Profiles of Eminent American Chemists. Sydney, N.S.W.: Litarvan Enterprises, 1986. Presents a short summary of Tishler’s life and work.

Waldron, Mitch. “Max Tishler: Worried Over Research’s Future.” Chemical and Engineering News 55, no. 15 (April 17, 1977): 38. A humorous but informative article based on Tishler’s acceptance speech for the American Institute of Chemists’ Gold Medal presented in New Orleans in March, 1977.