David Pressman, 1937
[Part 6 of 6 in our series exploring Linus Pauling’s work on the serological properties of simple substances, and the colleagues who assisted him in this work.]
After a meeting with Karl Landsteiner in 1936, Linus Pauling began serious investigations into the link between antibodies and antigens, compiling notes for what would eventually become his serological series, a collection of fifteen papers published during the 1940s. Landsteiner had specifically piqued Pauling’s curiosity on the question of the human body’s specificity mechanism – e.g., how could the body produce antibodies tailored to lock onto and fight specific antigens?
Pauling ultimately surmised that the answer lie in the shape of the molecules, and in the type and number of bonding sites. He described this as a “lock and key” mechanism, otherwise termed as molecular complementarity. Throughout this project, which made a significant impact on the modern study of immunology, Pauling enlisted the help of many undergraduate, graduate, and doctoral students, including a promising young scholar named David Pressman.
David Pressman was born in Detroit, Michigan in 1916. He attended Caltech as an undergraduate, studying under Pauling and completing his degree in 1937. He stayed in Pasadena for his doctorate, earning it in 1940. During this time, he became a part of Pauling’s quest to unravel the structure of proteins, and was particularly involved with the antibody and antigen work.
By this point, Pauling and his colleague Dan Campbell felt confident enough in what they had learned about antibody specificity to attempt creating artificial antibodies. Pauling was enthusiastic about the practical application that such an endeavor might promise for physicians. Warren Weaver, Pauling’s primary contact at the Rockefeller Foundation, which was funding the work, cautioned Pauling against becoming overconfident, but still granted him enough money to hire Pressman full-time. Thus began Pressman’s career in immunology.
At Pauling’s request, Pressman stayed on at Caltech as a post-doc, and during this time the two became friends. In 1943, after failing to prove that they could synthesize antibodies, Pauling’s research team changed their focus from understanding the structural components of antibodies and antigens, to looking for the binding mechanism that allowed antibodies to attach to specific antigens through Van der Waals bonds. One outcome of this was their development of the theory of complementarity, a “lock and key” model in which molecules fit together because of the high levels of specificity that they show for one another.
Pressman authored three papers with Pauling during this phase, including a very important one titled “The Nature of the Forces between Antigen and Antibody and of the Precipitation Reaction,” published in Physiological Reviews. In this paper, the researchers discussed the historical significance of immunology within the context of structural chemistry. Speaking of the tradition in which they worked, Pauling and his colleagues wrote that “two of the most important advances in the attack on the problem of the nature of immunological reactions were the discovery that the specific precipitate contains both antigen and antibody, and the discovery that antibodies, which give antisera their characteristic properties, are proteins.” In this paper, they also theorized that the immune system depends on structural and chemical forces to function.
Pressman (at right) in the lab, ca. early 1960s.
In 1947, Pressman decided to pursue an interest in cancer research and moved on to the Sloan Kettering Institute in New York City to investigate the use of radioactive tracers as they pertained to cancer treatment. The West Coast was never far from his thoughts however, and he often wrote back to friends comparing the two regions and asking for information about life in Pasadena. Of his new arrangements he observed, “The mechanics of living take a much greater part of the time in New York, so that I do not have as much time to do as much as I would like to or could do in Pasadena.”
Pressman’s first few years at Sloan-Kettering were difficult, not only because of the nature of the research that he was conducting – a continuation of the research that he started with Pauling – but because he was frequently forced to move both his lab and his residence, a source of continuous disruption for himself and his family. Sloan Kettering had just been established in the early 1940s and wasn’t formally dedicated until the year after Pressman moved there. Though it eventually became one of the nation’s leading biomedical research institutions, Pressman’s early experiences there coincided with institutional growing pains.
Eventually, as the environment at Sloan-Kettering became more stable, Pressman settled in to his position and provided Pauling with regular updates on his progress. The two often traded manuscripts back and forth, and each solicited technical advice from one another on their specific endeavors, which gradually grew further afield as time moved forward. At Kettering, Pressman continued to study antibody specificity and explored the potential use of radioactive antibodies for tumor localization to develop immunotoxins. In 1954, he left New York City for the Roswell Park Institution in Buffalo, remaining there until his death.
60th birthday greetings sent to Pauling by David and Reinie Pressman, February 1961.
Pauling and Pressman remained in frequent contact for many years, focusing their voluminous correspondence primarily on work that Pressman continued to do as an outgrowth of their time together in Pasadena. In July 1961, Pressman wrote that he and a colleague, Oliver Roholt, had potentially made a breakthrough with regard to the sequencing of the polypeptide chain associated with the region of specific binding sites in antibodies. He sent his manuscript, “Isolation of Peptides from an Antibody Site,” to Pauling for review prior to submission to Proceedings of the National Academy of Science. Pauling felt that the manuscript had been put together too quickly and challenged Pressman to do better. He annotated the manuscript with numerous suggestions, most of which Pressman adopted. Less than a week later, Pressman sent the manuscript back to Pauling with the corrections and Pauling transmitted it in to PNAS, where it was received favorably.
The late 1960s were a period of great activity and advancement for Pressman. In 1965, he received the Schoellkopf Medal, a prestigious award granted by the Western New York section of the American Chemical Society. In 1967, he became assistant director at Roswell and, in 1968, he published a book, The Structural Basis of Antibody Specificity. By all outside indications, Pressman’s life was going well.
In 1977 however, tragedy struck when Jeff Pressman, David and Reinie Pressman’s son, committed suicide at the age of 33. Jeff was an up-and-coming professor of political science at MIT, where he was well-liked by faculty and students. Up until a few months before his death, Jeff had seemed happy, both with his career and his life at home. In a letter to Pauling, Pressman described Jeff’s descent into depression as sudden, severe, and uncharacteristic. He also documented the events leading up to his son’s suicide, conveying that he and his wife had become increasingly convinced that the responsibility for the tragedy lay at the feet of a rheumatologist to whom Jeff had been seeking assistance for back pain.
Believing Jeff’s back pain to be primarily muscular in cause, the rheumatologist had prescribed Indocin in January 1977. According to multiple sources that Pressman later consulted, Indocin was a mood-changer, so much so that other patients had reported sudden depressive symptoms and, in severe cases, committed suicide a few months after starting the medication. To complicate matters, the rheumatologist had increased Jeff’s dose to a level that few patients could tolerate well, and had done so more rapidly than was advisable. When Jeff began complaining of insomnia, the rheumatologist prescribed two additional medications, both of which had the potential to worsen his depression. Jeff finally stopped taking Indocin, but the effects lingered. Jeff’s wife, Katherine, reported that Jeff had felt increasingly hopeless about his depression, even though he continued to work at MIT up until his death.
David Pressman’s former secretary, Cheryl Zuber, posing with a plaque mounted in Pressman’s honor at the Cancer Cell Center, Roswell Memorial Institute, 1981.
In the wake of Jeff Pressman’s death, his colleagues at MIT published a collection of political essays dedicated in his honor. The dedication specifically called out Jeff’s commitment to his students and his impact as a teacher. In it, his colleagues wrote, “He cared deeply about public affairs and immersed himself in them because he genuinely felt that government at its best could improve peoples’ lives.”
Nonetheless, the loss took its toll and, for David Pressman, the only source of solace that he could identify was a return to work. In 1978, his focus in the laboratory was on localizing radio-iodinated antitumor antibodies. He later wrote to Pauling about chronic shoulder pain that he was experiencing, as he was aware of Pauling’s vitamin research and was in search of an alternative to the shoulder replacement surgery that had been recommended by his physician. Pauling put forth an argument for a megadose of vitamins, but Pressman was eventually diagnosed with osteoarthritis. By the end of the year, he was slowing down, both in his work and in his correspondence.
Two years later, in June 1980, Pauling received the news that David Pressman had jumped from the roof of Roswell Park Memorial Institute. In a letter to Pauling informing him of her husband’s death, Reinie Pressman cast about for answers. She wrote at length about the health problems that he had been experiencing, including partial hearing loss, prostate trouble, and chronic problems associated with the osteoarthritis in his right shoulder. She also confided that “You were a significant part of Dave’s happier past.” Pauling replied in kind, stating
AdvertisementsI was very fond of David. Also, I owe much to him, because of the vigor and effectiveness with which he tackled scientific problems during the eight years that he worked with me. Much of the success of our program in immunochemistry was due to his contribution.
