The concept of immunity can be dated all the way back to the plague of Athens in 430 BCE, when Greek historian Thucydides noted that many people who had survived the disease in previous outbreaks appeared safe from its ravages. The first successful vaccine was in use by the end of the 18th century, but a molecular understanding of how immunity works was elusive to scientists for centuries. In the mid-20th century, Rockefeller Institute physician Henry G. Kunkel paved the way for modern immunological research with his uniquely clinical approach. For his numerous discoveries in immunology, Dr. Kunkel, now known as the father of immunopathology, received the 1975 Albert Lasker Basic Medical Research Award.
Dr. Kunkel spent the first several years of his career learning the techniques of protein chemistry and immunology and developing refined new analytical methods still in use today. His lifelong scientific priority, however, was as a physician. His insistence on solving medical mysteries by combining information gleaned directly from patients with molecular analysis in the laboratory — a highly unusual approach in immunology at the time — led him to discoveries that provided therapeutic solutions for several diseases and set down the standards by which the new discipline of clinical research was to develop. In the 1940s, autoimmunity — in which the immune system attacks the body’s own healthy cells — was a fairly new, untested concept, with little evidence to support it as a cause of pathology. Dr. Kunkel’s work provided the first proof of the phenomenon.
Investigating blood samples from patients with myeloma — a cancer of antibody-producing plasma cells — Dr. Kunkel drew a parallel that astonished immunologists and provided an unexpected means of studying immune cells. Though they are the product of cancerous cells, he found, myeloma proteins are directly analogous to normal immunoglobulin produced by normal gamma globulin proteins, and are therefore a model for the study of antibodies.
In the late 1950s, Dr. Kunkel introduced the concept of autoimmunity in the demonstrable context of disease with his studies of rheumatoid arthritis, a disease in which inflammation of the membranes lining joints can lead to destruction of the joints. He was the first to characterize the rheumatoid factor as an antibody, and his demonstration that rheumatoid factor 19S reacts with 7S gamma globulin, another antibody, proposed the existence of autoimmune complexity: the ability of an antibody to initiate an autoimmune reaction when combined with another molecule.
Dr. Kunkel’s initial experiments with RA patients failed to dispel the skepticism about either the existence of autoantibodies or, assuming their existence, their significance in disease. His additional studies with systemic lupus erythematosus (SLE) — an inflammatory disease of the connective tissue that can affect numerous organ systems including the skin, joints, kidneys and brain — uncovered several new autoantibodies and autoimmune complexes and demonstrated a direct correlation between the presence of the latter and the severity of disease progression. When he confirmed the presence of immune complexes not only in the bloodstream of patients but clustered near tissue injuries, he had effectively established SLE as the first immune complex disease.
Dr. Kunkel furthermore found that some of the autoimmune complexes discovered in SLE are formed by antibodies reacting not with other antibodies but with cellular components including DNA. He correctly theorized that the discovery of antiDNA antibodies could explain the phenomenon known as LE cells. Discovered in 1948, LE cells are those that have ingested nuclear material freed from other cells, and are commonly found in high concentrations in cases of certain autoimmune diseases. In the mid-1960s, Dr. Kunkel connected antiDNA antibodies to the common development of kidney failure in SLE patients.
Dr. Kunkel’s novel approach to the study of immunology vastly expanded our knowledge of how immune cells work and how they can go awry. In the laboratory, Dr. Kunkel’s work led directly to the solution of the basic structure of antibodies by Gerald M. Edelman, a graduate student of Dr. Kunkel in the late 1950s, who was awarded the 1972 Nobel Prize in Physiology or Medicine for his work. And on the medical end, Dr. Kunkel’s research with myeloma cells and gamma globulin led directly to the development of monoclonal antibody technology, in which any number of pure antibodies can be efficiently synthesized for therapeutic application by the fusing of normal plasma cells with immortal, benign tumor cells. Dr. Kunkel shared the 1975 Lasker Award with Frank Dixon of The Scripps Research Institute, Roger Guillemin of The Salk Institute and Andrew Schally of the Veterans Administration.
CAREER
Born in Brooklyn, New York, in 1916, Dr. Kunkel was the son of botanist Louis O. Kunkel, head of The Rockefeller Institute’s department of plant pathology. Dr. Kunkel received his medical degree in 1942 from The Johns Hopkins University School of Medicine. After a residency at Bellevue Hospital, he joined the United States Navy and served as a physician in Europe during World War II. After the war, he joined The Rockefeller Institute in 1945, becoming an assistant member in 1947, an associate member in 1949 and a full member and head of laboratory in 1952. He was named the Abby Rockefeller Mauzé Professor in 1976. With the exception of a year spent conducting research at the Biochemical Institute in Uppsala, Sweden, Dr. Kunkel spent the remainder of his career at Rockefeller. He served as president of the American Society for Clinical Investigation. He was an editor of The Rockefeller University Press’s Journal of Experimental Medicine from 1960 until his death and was a cofounding editor of Advances in Immunology. He died in 1983.