HISTORICAL FACULTY HIGHLIGHT
The Reclusive Revolutionary:
Dr. Elvin Kabat and His Legacy
Dr. Elvin A. Kabat, one of the founding fathers of modern immunochemistry, was a respected and beloved member of the faculty in the Department of Microbiology & Immunology for over half a century. In addition to his remarkable contributions to immunology, including over 470 publications and several leading textbooks, Kabat was an outstanding teacher and mentor, whose students, including Nobel Laureate Baruj Benacerraf, went on to make outstanding contributions to the field. The extent of Kabat’s contributions are astounding, particularly considering the unexpected challenges his career faced.
From both the bench and beyond, Dr. Elvin Kabat had an immeasurable impact, leaving behind a legacy that remains with us to this day.
Kabat began working in Dr. Michael Heidelberger’s immunochemistry lab at Columbia in 1933, at the age of 18, first as a lab assistant, then as a graduate student. Kabat was Dr. Heidelbergers’s first student to be awarded a Ph.D. in 1937, for his graduate research on the immunochemical and physical properties of antibodies. Afterwards, Kabat spent a year as a postdoctoral researcher, funded by the Rockefeller Foundation, in the laboratory of The Svedburg at the Institute of Physical Chemistry in Uppsala, Sweden, where he worked with Arne Tiselius and performed the first immunochemical characterization of immunoglobulin G, using electrophoresis to show that immunoglobulins comprise the “gamma globulin” fraction of human serum. In late 1938, Kabat returned to the U.S. as an Instructor in the Department of Pathology at Cornell University, where he worked on purifying Rous sarcoma virus. In 1941, Kabat returned to Columbia University as a Research Associate in the Department of Biochemistry assigned to Neurology, where he was to perform research on multiple sclerosis.
The involvement of the United States in World War II starting in December 1941 had a major impact on Kabat’s research and career. Kabat’s research shifted to working on immunization against meningitis, developing more accurate tests for syphilis, and performing classified research for the National Defense Research Committee (NDRC) on detecting and neutralizing the plant toxin ricin. Part of this classified research involved immunizing a pair of horses with ricin to prepare a stock of antitoxin, which Kabat had to purchase at a horse auction and keep stabled at Rockefeller University at an exorbitant monthly rate. When Kabat tried to cut costs by selling the horse that failed to produce antibodies, he had to justify its lower resale value to the NDRC in the following manner: “...as a consequence of the numerous injections which the horse had received, it had developed many unsightly blemishes and had acquired a very intractable disposition, which in my judgment had reduced its value from $125 to $25.” This incident eventually led to a ruling that government supported investigators could dispose of research animals in any way they saw fit, including sale.
During the war, Kabat hired Hilda Kaiser to work in his laboratory. Her husband, Samuel Kaiser, had been dismissed from Brooklyn College as a consequence of the New York State Legislature’s anti-communist Rapp Coudert Committee, one of many similar committees that formed between WWII and the end of the McCarthy era. Kabat also began to write his seminal textbook, Experimental Immunochemistry, with Manfred Mayer, and served as a consultant for the US Army at Fort Detrick, writing a report with Theodor Rosebury on potential biological warfare agents. Kabat and Rosebury had voluntarily refrained from publishing the report during the war, but once the war ended, they obtained clearance from the War Department and Columbia University to publish their review. The publication resulted in a burst of publicity, including an article in Time magazine that implied that Kabat was a communist supporter and had published classified information. Although this was untrue, it immediately resulted in an FBI investigation of Kabat, with FBI agents interviewing his landlord and opening his mail.
In 1946, after being passed over for promotion to Assistant Professor from Research Associate in the Department of Biochemistry, Kabat accepted a faculty appointment as an Assistant Professor in the Department of Bacteriology (now the Department of Microbiology & Immunology). By 1947, Kabat’s new laboratory was performing research on blood group substances, encephalomyelitis, and quantitating allergic reactions. In 1948 Kabat was promoted to Associate Professor, and began to perform research on developing diagnostic assays for multiple sclerosis, initially funded by the National Multiple Sclerosis Society, and then Public Health Service. Kabat also began collaborating on histochemical localization of enzymes with Abner Wolf at the Bronx Veterans Administration (VA) Hospital as an attending consultant. This collaboration had unexpected consequences.
In 1947, after Kabat had started working at the VA, an Executive Order was issued by President Truman mandating loyalty investigations of every Federal employee, formation of loyalty boards, and the development of a central master index of each person investigated. A former colleague of Kabat’s in Sweden, biochemist and Nobel Laureate James B. Sumner, informed the FBI that he suspected Kabat of being a communist sympathizer. This triggered a series of investigations of Kabat by the FBI and the Bronx VA Hospital Loyalty Board, and the dismissal of Kabat from his VA position by the hospital loyalty board. Kabat appealed his dismissal to the Presidential Loyalty Review Board, which reversed the decision and reinstated him, but continued pressure led Kabat to resign his VA position and abandon his work on the histochemical localization of enzymes. The hospital loyalty board had also issued a recommendation to the Passport Office that Kabat not be allowed to travel, after which Kabat’s passport was rescinded, and not returned upon his reinstatement. As a result, Kabat was not able to attend international conferences or travel internationally until 1955, after which a DC district court decision, Boudin v. Dulles, held that passports could not be denied based on undisclosed information.
Fortunately for Kabat, he had the full support of the Department of Microbiology & Immunology during this difficult period. When Harry M. Rose was appointed Chair of the department in 1951, Rose accepted the position under the conditions that Kabat would be promoted to full Professor and have his salary supported by departmental funds, which took place in 1952. Kabat also received support from an unexpected source – the US Navy. In 1950, Kabat was invited to speak at the Naval Biological Laboratory, the Navy’s equivalent of Camp Detrick. In 1952, the Office of Naval Research offered Kabat a grant for immunochemical criteria of purity of proteins and polysaccharides, which as it turned out, was most fortuitous. A year later, in 1953, at the peak of McCarthy era hysteria, the Public Health Service (at the time, the equivalent to the NIH) refused to renew Kabat’s research grant on multiple sclerosis due to the political climate, suggesting that perhaps another name could be substituted as the responsible investigator, which Kabat refused to do. At the time, Kabat had developed the first reliable immunodiagnostic test for multiple sclerois, developed a successful animal model of multiple sclerosis, established the autoimmune character of this disease, and was running the only monkey colony in the world devoted to multiple sclerosis. Public Health Service also terminated Kabat’s blood group grant. Kabat never again requested or accepted funding from them. His future research would be funded by the Office of Naval Research and the National Science Foundation.
Despite the tremendous blow suffered to two of his primary areas of research from the sudden termination of these grants, Kabat continued to perform pioneering research. In 1951, Kabat showed that dextran, commonly used as a blood plasma substitute at the time, could provoke an immune response in humans. He took advantage of his expertise in carbohydrate chemistry to test the impact of a series of oligosaccarides on dextran binding antibodies, and used this data to provide the first estimates of the size and shape of an antibody’s antigen binding site, confirmed decades later by X-ray crystallography.
In 1970, Kabat began to perform bioinformatics research in immunology, decades before sequence analysis became widely accepted. He realized that the amino acid sequence data for immunoglobulins now being published could be used to predict the locations of antigen binding regions. Kabat developed the Wu-Kabat plot with Tai Te Wu, which identified hypervariable and framework regions, and used this data to correctly predict the location of antigen binding regions in antibodies. Lacking modern tools, Kabat had to locate, enter and align immunoglobulin sequences from the published literature by hand. The data was eventually distributed in collaboration with the NIH as a textbook, called Sequences of Proteins of Immunological Interest, which had an enourmous impact on the field of immunology. In 1974, Kabat spent a year at the NIH as a Fogerty Scholar, and subsequently divided his time doing research at Columbia and working on immunological sequence data at the NIH.
Kabat was awarded the Louisa Gross Horwitz Prize by Columbia University in 1977 along with Michael Heidelberger and Henry G. Kunkel, and in 1991 was awarded the National Medal of Science, the nation’s highest award for scientific achievement. This last award had particular significance to Kabat, given his shabby treatment at the hands of the government and Public Health Service in the 1950s.
Dr. Elvin A. Kabat remained an active member of the Department of Microbiology & Immunology until his death in 2000. He is deeply missed and remembered by his colleagues in Microbiology & Immunology not only for his outstanding scientific mind but also for his high standards, his forthrightness, and his wonderful sense of humor.
In 2001, the families of Dr. Michael Heidelberger and Dr. Elvin A. Kabat, in conjunction with Department of Microbiology & Immunology and the University, formally established the Heidelberger-Kabat Distinguished Lectureship in Immunology to honor Drs. Heidelberger and Kabat, longtime colleagues and friends, by sponsoring an annual lecture by a scientist representing the best current research in immunology. The Heidelberger-Kabat Lecture has emerged as one of the country’s premier forums for the discussion of new developments and discoveries in immunochemistry.