Miguel A. Ondetti

Miguel A. Ondetti begins this interview by describing his parents' immigrant background and work in Argentina, his early interests in chemistry, and his education at vocational school in Buenos Aires. Upon high school graduation, Ondetti began work as a bookkeeper, continuing studies at night to meet university entrance requirements. He began chemistry coursework at the University of Buenos Aires while supporting himself with accounting work for the government. Here, he describes his broad training in chemistry, Argentina's political climate, and his Ph.D. scholarship and carbohydrates research for V. Deulofeu at The Squibb Institute. Upon graduation in 1957, Ondetti explored other opportunities before accepting a position with Squibb's alkaloid isolation group, where he remained until 1960, when after much consideration he accepted a job with Squibb, New Jersey. In New Jersey, Ondetti worked in the peptide chemistry group, synthesizing the nonapeptide bradykinin under M. Bodanszky, with whom he co-wrote Peptide Synthesis. He discusses adjusting to life and work in the U.S. and his advancement in the peptide synthesis field and promotion to group head when Bodanszky pursued a career in academia. Ondetti was part of a group effort to synthesize gastrointestinal hormones, particularly secretin, a peptide amide that stimulates the pancreas to secrete bicarbonate and water. While Bodanszky pursued stepwise synthesis of the peptide, Ondetti worked with E. Sabo on fragment condensation. Both approaches eventually led to fully active synthetic secretin; the fragment condensation approach was used to obtain synthetic secretin for clinical studies, the results of which discouraged further development. Next, Ondetti worked with Sabo to synthesize cholecystokinin, which stimulates contraction of the gall bladder and secretion of enzymes from the pancreas. Here he describes problems with the synthetic peptide's development and its eventual use as a diagnostic agent. Also discussed is the importance of his relationships with Sabo and Z. Horovitz. In 1967, A. D. Welch became Squibb's president, and changes in company research agendas led Ondetti to work on peptidase inhibitors. Ondetti describes acquiring venom for isolation of enzyme inhibitors, isolating angiotensin converting enzyme inhibitors, and learning to isolate and sequence peptides in competition with researchers at Brookhaven National Laboratories. In 1973, for practical reasons, Squibb's angiotensin converting enzyme (ACE) inhibitor work officially ended, but Ondetti's interest in the subject continued. Prompted by discoveries of L. D. Byers and R. Wolfenden and interactions with D. Cushman, Ondetti decided to pursue synthesis of succinyl-L-proline, which was found to potentiate the contractile activity of bradykinin. Continuing work in this direction, Ondetti and Sabo started making hydroxamic acids with better activity and eventually sulfhydryl compounds with great activity. After continued research, this work evolved into captopril. Here, Ondetti describes human trials of this drug, problems with FDA approval, the effectiveness of captopril for hypertension treatment, and follow-up research leading to new therapeutic agents. The interview closes with Ondetti's reflections on the fields of chemistry and pharmaceutical research, and his own career; highlighted are notions of success and rewards, collaboration between industry and academia, rational drug design, and leadership.

Department of Energy, Argentina Government

1948 - 1957 Bookkeeper

University of Buenos Aires

1957 - 1960 Instructor

Catholic Institute for Teachers

1957 - 1960 Professor

The Squibb Institute for Medical Research, Argentina

1957 - 1960 Senior Research Chemist

The Squibb Institute for Medical Research, New Jersey

1960 - 1966 Senior Research Chemist

The Squibb Institute for Medical Research, New Jersey

1966 - 1973 Research Group Leader, Peptide Synthesis

The Squibb Institute for Medical Research, New Jersey

1973 - 1976 Section Head, Peptides, Steroids, and Antibiotic Research

The Squibb Institute for Medical Research, New Jersey

1976 - 1980 Director, Department of Biological Chemistry

The Squibb Institute for Medical Research, New Jersey

1980 - 1981 Associate Director, Chemical and Microbiological Research

The Squibb Institute for Medical Research, New Jersey

1981 - 1983 Vice President, Basic Research

The Squibb Institute for Medical Research, New Jersey

1984 - 1989 Vice President of Research, Cardiopulmonary Diseases

The Squibb Institute for Medical Research, New Jersey

1989 - 1990 Senior Vice President of Research, Cardiovascular Diseases

The Squibb Institute for Medical Research, New Jersey

1990 - 1991 Senior Vice President, Cardiovascular and Metabolic Diseases

The Squibb Institute for Medical Research, New Jersey

1991 Retired

James J. Bohning

James J. Bohning is professor emeritus of chemistry at Wilkes University, where he was a faculty member from 1959 to 1990. He served there as chemistry department chair from 1970 to 1986 and environmental science department chair from 1987 to 1990. Bohning was chair of the American Chemical Society’s Division of the History of Chemistry in 1986; he received the division’s Outstanding Paper Award in 1989 and has presented more than forty papers at national meetings of the society. Bohning was on the advisory committee of the society’s National Historic Chemical Landmarks Program from its inception in 1992 through 2001 and is currently a consultant to the committee. He developed the oral history program of the Chemical Heritage Foundation, and he was the foundation’s director of oral history from 1990 to 1995. From 1995 to 1998, Bohning was a science writer for the News Service group of the American Chemical Society. He is currently a visiting research scientist and CESAR Fellow at Lehigh University. In May 2005, he received the Joseph Priestley Service Award from the Susquehanna Valley Section of the American Chemical Society.