778
PRESENTATION OF THE ACADEMY MEDAL TO HENRY G. KUNKEL, M.D.* ALEXANDER G. BEARN, M.D. Professor of Medicine Cornell University Medical College Physician-in- Chief The New York Hospital New York, N.Y.
T is the privilege of the Academy each year to award a medal to an 1 individual who has contributed outstandingly to the advance of medical knowledge. It is a source of great personal joy to me that this year the Academy has awarded this medal to Dr. Henry G. Kunkel, Abby Rockefeller Mauze Professor of Medicine and Immunology at the Rockefeller University. He is a splendid choice. In previous years Peyton Rous, Oswald Avery, and Richard Shope, all of the Rockefeller University, received this award and Henry Kunkel is assuredly of their number. His scientific contributions in the field of immunology are outstanding, not only in their own right, but because they have become integrated into the very fabric of modern medicine wherever it is practiced in the world today. Henry Kunkel was born in Brooklyn on September 9, 1916, the son of Dr. Louis Otto Kunkel, a distinguished plant pathologist who established the Division of Plant Pathology at the Rockefeller Institute for Medical Research and in whose laboratory Dr. Wendell Stanley carried out the work on the tobacco mosaic virus for which he received a Nobel Prize. It is not hard to see that Henry Kunkel's early interest in science had deep environmental and hereditary roots. In 1938 he received the A.B. degree from Princeton University and decided to embark on a career in medicine. His scientific interests, already kindled by his home environment and his days at Princeton, were stimulated still further at the Johns Hopkins Medical School from which he
*Presented at the Stated Meeting of the New York Academy of Medicine held April 14,
1977.
Address for reprint requests: 450 East 69th Street, New York, N.Y. 10021.
Bull. N.Y. Acad. Med.
PRESENTATION OF THE ACADEMY MEDAL
779
obtained his M.D. degree in 1942. While still in medical school, he worked on a singular study-to which he would never return-the effect of the enzyme uricase on the level of uric acid in blood. Dr. Kunkel's house staff training was undertaken in the intellectually lively atmosphere of Professor William S. Tillett's service at Bellevue Hospital, where special attention was paid to research in microbial disease. Further training in medicine was put aside temporarily when Kunkel entered the military to serve in the Marine Corps during World War II. After the war he returned to civilian life and his career in medicine. In 1945, at the urging of Dr. William Tillett, he entered the Rockefeller Institute for Medical Research to work in Dr. Charles Hoagland's laboratory and he has remained at this remarkable institution, made the more remarkable by his presence, for his entire scientific career. On entering the laboratory Dr. Kunkel became interested in liver disease, and abnormalities in the workings of that versatile organ occupied the first decade of his scientific life. Dr. Kunkel soon became aware that the methods employed to investigate serum proteins were grossly inadequate, so he journeyed to Uppsala in Sweden, to work with Arne Tiselius, the Nobel laureate. He quickly mastered free solution electrophoresis and, whifk in Sweden, invented a new and ingenious method of preparative electrophoresis using starch as a supporting medium. This technique, like so many devised by Henry Kunkel, is brilliantly simple and is still applied throughout the 'world in various guises. It has revolutionized and made quantitative many aspects of clinical investigation. When he returned to Rockefeller University, Dr. Kunkel continued to investigate liver disease using his newly acquired techniques; in so doing, he was able to identify a group of young women with cirrhosis of the liver of an unusual etiology in whom serum gamma globulin levels were extremely high. This interesting group of patients with cirrhosis of the liver, called active chronic HB antigen negative lupoid hepatitis in many parts of the world, is often irreverently abbreviated by those who are aware of Dr. Kunkel's work as "Kunkel's girls." In 1951 Dr. Kunkel published new and fundamental observations on the relation between certain myeloma proteins and normal gammaglobulins.* He showed that antisera to normal immunoglobulin reacted with myeloma *Kunkel, H.G., Slater, R.J., and Good, R.A.: Relation between certain myeloma proteins and normal gamma globulin. Proc. Soc. Exp. Biol. Med. 76: 190, 1951.
Vol. 53, No. 9, November 1977
780
7XU
A. A. G. 6. BEARN
BEARN~~~~~~~~~~~~~~~~~~~~~~~~~
:M"w
HENRY G. KUNKEL, M.D.
Bull. N.Y. Acad. Med.
PRESENTATION OF THE ACADEMY MEDAL
781
proteins from four different patients, while the fifth myeloma protein did not show this reaction. This latter myeloma protein, which had a faster electrophoretic mobility than normal gamma globulin, indicated the existence of a previously undiscovered class of immunoglobulins, later to be termed IgA. After demonstrating the antigenic and structural relations between myeloma proteins and normal immunoglobulins, Dr. Kunkel pointed out that it should be possible to use myeloma proteins to elucidate the structure of normal gamma globulin. This proved to be brilliantly true. In 1955 Dr. Kunkel made the extremely significant observation that normal blood contains two forms of hemoglobin and named the minor component of normal hemoglobin hemoglobin A2. He discovered that the A., level was increased in thalassemia minor, and this remains one of the most useful diagnostic aids in the investigation of the hemoglobinopathies. In 1955 Dr. Kunkel described the existence of two major classes of myeloma protein: one corresponded to IgG and cross-reacted with normal immunoglobulin; the other was less closely related to IgG, tended to form polymers, and tended to have the electrophoretic mobility of beta globulin. The carbohydrate contents of these proteins were greater than that of IgG, and antiserum to these proteins absorbed with normal IgG still reacted with a protein in normal serum. These observations became the first description of normal IgA. At that time it was believed that 19S gamma globulin was an aggregate, but Kunkel showed that it was distinct from IgG, both in its antigenic properties and in its carbohydrate content. These studies led directly to the definition of rheumatoid factors as IgM and IgG antibodies to immunoglobulin. Many other contributions to immunogenetics made by Dr. Kunkel and his colleagues could be cited. Dr. Kunkel recognized and isolated a new complement component, Cq. He has characterized several new genetic markers and identified the first IgA marker in human immunoglobulin. He was among the first to show that the rheumatoid factor is an autoantibody to immunoglobulin, and that it occurs in the circulation of patients in the form of a soluble complex, autologous IgG. He found that in both rheumatoid arthritis and systemic lupus erythematosus complexes occur which have the ability to activate the complement system and which may lead to tissue injury of the host. Most important, lupus nephritis was shown by Dr. Kunkel to represent an immune complex nephritis in which the deposited antigen is DNA. The impact of Dr. Kunkel's work on immunology and medicine is monumental. Vol. 53, No. 9, November 1977
782
782
A. G. BEARN A. 6.
BEARN~~~~~~~~~~~~~~~~~~~~~~~~~~
Now that I have emphasized and outlined some of Dr. Kunkel's scientific discoveries, I shall refer to another quality that makes him unique among clinical investigators. Dr. Kunkel has done more to train the young generation of immunologists than anyone else I know. At any immunological meeting here or abroad it always seems that most of the papers not given by Kunkel and his team are given by his past students. Henry Kunkel has a unique capacity to work with young people and bring out the best in them. Many totally unfledged investigators, and I count myself fortunate to have been one of them, have entered Dr. Kunkel's laboratory without experience and with much scientific naivete. With his encouragement and guidance all those who worked in his laboratory somehow performed better than they really were. His enthusiasm for new knowledge is contagious. His extreme generosity toward his younger colleagues is legendary; he tried always to make us believe that what clearly were his good ideas were really our own. The simple but stirring theme running through Henry Kunkel's scientific life is clear: the rigorous investigation of human disease both clinically and experimentally. It has been an imaginative trail of research, doggedly pursued wherever it appeared promising and the time appeared ripe. Henry Kunkel is a scientist who, even while pursuing investigations at the most basic level, is always on the lookout for clinical and therapeutic implications. His bibliography is replete with clinically relevant studies, but they differ sharply from most such studies by the originality of the questions asked, the precision of the scientific observations recorded, and the cautious modesty exercised in their interpretation. Dr. Kunkel's unerring nose for detecting a good scientific problem is matched only by his celerity in recognizing a bad one. One of the undoubted secrets of Dr. Kunkel's success is that his fertile and imaginative mind, coupled with his extraordinary ability in the laboratory, has kept him at the bench long after those of similar age are consumed by what Jan Waldenstiom once called "hyperadministration." His advice is widely sought and he is asked to serve on many committees, but he is not really a born committeeman; he is not one to sit around tables covered in green baize, scattered with sharp pencils, sipping iced water hour after hour. Yet, those who know him best sometimes feel that, in reality, the ideal scientific committee would have Henry Kunkel as chairman and two other members both in bed with the flu. Henry Kunkel is a scientist's scientist and an immunologist's im-
Bull. N.Y. Acad. Med.
PRESENTATION OF THE ACADEMY MEDAL
783
munologist. He continues to work with the same vigor as he did when he entered the Rockefeller Institute some 32 years ago. His recent pioneering work on the new immunology, the immunology of the lymphocyte, is not only enriching our understanding of the biology of the lumphocyte itself, but is giving important and novel insight into an understanding of leukemia and many of the immunodeficiency diseases. He has received many honors and awards, including the Gairdner Foundation Annual Award in 1962 and the Albert Lasker Medical Research Award in 1975. In 1973 he was awarded the Modern Medicine Distinguished Service Award for his work in developing procedures for the identification of immunological phenomena. He has received the T. Duckett Jones Award of the Helen Hay Whitney Foundation and the Passano Foundation Award in recognition of his pioneering research on human immunoglobulins. The University of Uppsala in Sweden conferred upon him the degree of Doctor of Medicine honoris causa. He is a member of the National Academy of Sciences, the Association of American Physicians, the American Academy of Arts and Sciences, as well as a charter member of the Institute of Medicine of the National Academy of Sciences. He served as president of both the American Society for Clinical Investigation and the American Association of Immunologists. Since the New York Academy of Medicine is a New York institution it gives me much pleasure to reflect that our awardee tonight is a native New Yorker; he has remained in this city all his scientific life. From his laboratory at the Rockefeller University in this city the fruits of his labors and those of his colleagues have contributed immeasurably to our understanding of the science of immunology and have advanced internal medicine throughout the world.
Vol. 53, No. 9, November 1977
PRESENTATION OF THE ACADEMY MEDAL TO HENRY G. KUNKEL, M.D.* ALEXANDER G. BEARN, M.D. Professor of Medicine Cornell University Medical College Physician-in- Chief The New York Hospital New York, N.Y.
T is the privilege of the Academy each year to award a medal to an 1 individual who has contributed outstandingly to the advance of medical knowledge. It is a source of great personal joy to me that this year the Academy has awarded this medal to Dr. Henry G. Kunkel, Abby Rockefeller Mauze Professor of Medicine and Immunology at the Rockefeller University. He is a splendid choice. In previous years Peyton Rous, Oswald Avery, and Richard Shope, all of the Rockefeller University, received this award and Henry Kunkel is assuredly of their number. His scientific contributions in the field of immunology are outstanding, not only in their own right, but because they have become integrated into the very fabric of modern medicine wherever it is practiced in the world today. Henry Kunkel was born in Brooklyn on September 9, 1916, the son of Dr. Louis Otto Kunkel, a distinguished plant pathologist who established the Division of Plant Pathology at the Rockefeller Institute for Medical Research and in whose laboratory Dr. Wendell Stanley carried out the work on the tobacco mosaic virus for which he received a Nobel Prize. It is not hard to see that Henry Kunkel's early interest in science had deep environmental and hereditary roots. In 1938 he received the A.B. degree from Princeton University and decided to embark on a career in medicine. His scientific interests, already kindled by his home environment and his days at Princeton, were stimulated still further at the Johns Hopkins Medical School from which he
*Presented at the Stated Meeting of the New York Academy of Medicine held April 14,
1977.
Address for reprint requests: 450 East 69th Street, New York, N.Y. 10021.
Bull. N.Y. Acad. Med.
PRESENTATION OF THE ACADEMY MEDAL
779
obtained his M.D. degree in 1942. While still in medical school, he worked on a singular study-to which he would never return-the effect of the enzyme uricase on the level of uric acid in blood. Dr. Kunkel's house staff training was undertaken in the intellectually lively atmosphere of Professor William S. Tillett's service at Bellevue Hospital, where special attention was paid to research in microbial disease. Further training in medicine was put aside temporarily when Kunkel entered the military to serve in the Marine Corps during World War II. After the war he returned to civilian life and his career in medicine. In 1945, at the urging of Dr. William Tillett, he entered the Rockefeller Institute for Medical Research to work in Dr. Charles Hoagland's laboratory and he has remained at this remarkable institution, made the more remarkable by his presence, for his entire scientific career. On entering the laboratory Dr. Kunkel became interested in liver disease, and abnormalities in the workings of that versatile organ occupied the first decade of his scientific life. Dr. Kunkel soon became aware that the methods employed to investigate serum proteins were grossly inadequate, so he journeyed to Uppsala in Sweden, to work with Arne Tiselius, the Nobel laureate. He quickly mastered free solution electrophoresis and, whifk in Sweden, invented a new and ingenious method of preparative electrophoresis using starch as a supporting medium. This technique, like so many devised by Henry Kunkel, is brilliantly simple and is still applied throughout the 'world in various guises. It has revolutionized and made quantitative many aspects of clinical investigation. When he returned to Rockefeller University, Dr. Kunkel continued to investigate liver disease using his newly acquired techniques; in so doing, he was able to identify a group of young women with cirrhosis of the liver of an unusual etiology in whom serum gamma globulin levels were extremely high. This interesting group of patients with cirrhosis of the liver, called active chronic HB antigen negative lupoid hepatitis in many parts of the world, is often irreverently abbreviated by those who are aware of Dr. Kunkel's work as "Kunkel's girls." In 1951 Dr. Kunkel published new and fundamental observations on the relation between certain myeloma proteins and normal gammaglobulins.* He showed that antisera to normal immunoglobulin reacted with myeloma *Kunkel, H.G., Slater, R.J., and Good, R.A.: Relation between certain myeloma proteins and normal gamma globulin. Proc. Soc. Exp. Biol. Med. 76: 190, 1951.
Vol. 53, No. 9, November 1977
780
7XU
A. A. G. 6. BEARN
BEARN~~~~~~~~~~~~~~~~~~~~~~~~~
:M"w
HENRY G. KUNKEL, M.D.
Bull. N.Y. Acad. Med.
PRESENTATION OF THE ACADEMY MEDAL
781
proteins from four different patients, while the fifth myeloma protein did not show this reaction. This latter myeloma protein, which had a faster electrophoretic mobility than normal gamma globulin, indicated the existence of a previously undiscovered class of immunoglobulins, later to be termed IgA. After demonstrating the antigenic and structural relations between myeloma proteins and normal immunoglobulins, Dr. Kunkel pointed out that it should be possible to use myeloma proteins to elucidate the structure of normal gamma globulin. This proved to be brilliantly true. In 1955 Dr. Kunkel made the extremely significant observation that normal blood contains two forms of hemoglobin and named the minor component of normal hemoglobin hemoglobin A2. He discovered that the A., level was increased in thalassemia minor, and this remains one of the most useful diagnostic aids in the investigation of the hemoglobinopathies. In 1955 Dr. Kunkel described the existence of two major classes of myeloma protein: one corresponded to IgG and cross-reacted with normal immunoglobulin; the other was less closely related to IgG, tended to form polymers, and tended to have the electrophoretic mobility of beta globulin. The carbohydrate contents of these proteins were greater than that of IgG, and antiserum to these proteins absorbed with normal IgG still reacted with a protein in normal serum. These observations became the first description of normal IgA. At that time it was believed that 19S gamma globulin was an aggregate, but Kunkel showed that it was distinct from IgG, both in its antigenic properties and in its carbohydrate content. These studies led directly to the definition of rheumatoid factors as IgM and IgG antibodies to immunoglobulin. Many other contributions to immunogenetics made by Dr. Kunkel and his colleagues could be cited. Dr. Kunkel recognized and isolated a new complement component, Cq. He has characterized several new genetic markers and identified the first IgA marker in human immunoglobulin. He was among the first to show that the rheumatoid factor is an autoantibody to immunoglobulin, and that it occurs in the circulation of patients in the form of a soluble complex, autologous IgG. He found that in both rheumatoid arthritis and systemic lupus erythematosus complexes occur which have the ability to activate the complement system and which may lead to tissue injury of the host. Most important, lupus nephritis was shown by Dr. Kunkel to represent an immune complex nephritis in which the deposited antigen is DNA. The impact of Dr. Kunkel's work on immunology and medicine is monumental. Vol. 53, No. 9, November 1977
782
782
A. G. BEARN A. 6.
BEARN~~~~~~~~~~~~~~~~~~~~~~~~~~
Now that I have emphasized and outlined some of Dr. Kunkel's scientific discoveries, I shall refer to another quality that makes him unique among clinical investigators. Dr. Kunkel has done more to train the young generation of immunologists than anyone else I know. At any immunological meeting here or abroad it always seems that most of the papers not given by Kunkel and his team are given by his past students. Henry Kunkel has a unique capacity to work with young people and bring out the best in them. Many totally unfledged investigators, and I count myself fortunate to have been one of them, have entered Dr. Kunkel's laboratory without experience and with much scientific naivete. With his encouragement and guidance all those who worked in his laboratory somehow performed better than they really were. His enthusiasm for new knowledge is contagious. His extreme generosity toward his younger colleagues is legendary; he tried always to make us believe that what clearly were his good ideas were really our own. The simple but stirring theme running through Henry Kunkel's scientific life is clear: the rigorous investigation of human disease both clinically and experimentally. It has been an imaginative trail of research, doggedly pursued wherever it appeared promising and the time appeared ripe. Henry Kunkel is a scientist who, even while pursuing investigations at the most basic level, is always on the lookout for clinical and therapeutic implications. His bibliography is replete with clinically relevant studies, but they differ sharply from most such studies by the originality of the questions asked, the precision of the scientific observations recorded, and the cautious modesty exercised in their interpretation. Dr. Kunkel's unerring nose for detecting a good scientific problem is matched only by his celerity in recognizing a bad one. One of the undoubted secrets of Dr. Kunkel's success is that his fertile and imaginative mind, coupled with his extraordinary ability in the laboratory, has kept him at the bench long after those of similar age are consumed by what Jan Waldenstiom once called "hyperadministration." His advice is widely sought and he is asked to serve on many committees, but he is not really a born committeeman; he is not one to sit around tables covered in green baize, scattered with sharp pencils, sipping iced water hour after hour. Yet, those who know him best sometimes feel that, in reality, the ideal scientific committee would have Henry Kunkel as chairman and two other members both in bed with the flu. Henry Kunkel is a scientist's scientist and an immunologist's im-
Bull. N.Y. Acad. Med.
PRESENTATION OF THE ACADEMY MEDAL
783
munologist. He continues to work with the same vigor as he did when he entered the Rockefeller Institute some 32 years ago. His recent pioneering work on the new immunology, the immunology of the lymphocyte, is not only enriching our understanding of the biology of the lumphocyte itself, but is giving important and novel insight into an understanding of leukemia and many of the immunodeficiency diseases. He has received many honors and awards, including the Gairdner Foundation Annual Award in 1962 and the Albert Lasker Medical Research Award in 1975. In 1973 he was awarded the Modern Medicine Distinguished Service Award for his work in developing procedures for the identification of immunological phenomena. He has received the T. Duckett Jones Award of the Helen Hay Whitney Foundation and the Passano Foundation Award in recognition of his pioneering research on human immunoglobulins. The University of Uppsala in Sweden conferred upon him the degree of Doctor of Medicine honoris causa. He is a member of the National Academy of Sciences, the Association of American Physicians, the American Academy of Arts and Sciences, as well as a charter member of the Institute of Medicine of the National Academy of Sciences. He served as president of both the American Society for Clinical Investigation and the American Association of Immunologists. Since the New York Academy of Medicine is a New York institution it gives me much pleasure to reflect that our awardee tonight is a native New Yorker; he has remained in this city all his scientific life. From his laboratory at the Rockefeller University in this city the fruits of his labors and those of his colleagues have contributed immeasurably to our understanding of the science of immunology and have advanced internal medicine throughout the world.
Vol. 53, No. 9, November 1977
