899
PRESENTATION OF THE ACADEMY MEDAL TO MACLYN McCARTY, M.D.* RICHARD M. KRAUSE, M.D. Director National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, Maryland is a personal joy to have been asked to pay tribute tonight to Maclyn McCarty, the 1979 recipient of the Academy Medal. I am one of a privileged group who has worked closely with Mac, and my purpose this evening is to describe briefly the man and his work. Mac is a son of the midwest, but it was first at Stanford University and later at Johns Hopkins University that he received the academic preparation on which his whole research career has been based. It is probably safe to say that his early schooling in the midwest had less influence, because at least one of his high school years was spent at Culver Military Academy, not especially noted as a campus where ideas flourish. But I suspect, Mac, that just enough of the military spit and polish you learned there was admired much later by Tom Rivers, then in the United States Navy as a commodore of the Rockefeller Institute Navy unit, a unit which you joined as a lieutenant, later rising to lieutenant commander. I have always wondered if your promotion to lieutenant commander was due in part, at least, to your early training at Culver! At Stanford Dr. McCarty was introduced to biochemistry. Later, at Hopkins, his preparation in this science extended beyond the usual medical curriculum. Throughout his career biochemistry has been on the cutting edge of his research. Yet, it must be added, his approach has never been just biochemical. It has always been tempered with a search for biological principles that in the end may have medical significance. He acquired this appreciation for the intricate nature of medical problems during three years of pediatric training at Harriet Lane. Then, after a year with Dr. Tillet at New York University, he arrived at Dr. O.T. Avery's laboratory at The Rockefeller Institute for Medical Research in 1941. There he rapidly rose through the ranks and was appointed member and physician in 1950. In
IT
*Presented at the Stated Meeting of the New York Academy of Medicine held April 19, 1979.
Vol. 55, No. 10, November 1979
900
KRAUSE R. M. KRAUSE
R. M.
900
NI .\(.I.)
I
N
M )
.
%. 1. 1).
,
Bull. N.Y. Acad. Med.
ACADEMY MEDAL
l~ ~~~~~~CDM
901 0
1960 he accepted responsibility for the leadership of the Hospital as physician-in-chief and later as vice-president, serving as an advisor and counselor to both Dr. Bronk and Dr. Seitz. It had been my initial intention to mention only in passing Dr. McCarty's research with Avery on the transformation of the pneumococcus. The story has been widely told recently-by Rene Dubos in his book on The Professor, the Institute and DNA and now most recently in The Ninth Day of Creation, by Horace Freeland Judson. And while I have, for personal reasons, a desire to focus especially on Dr. McCarty's work on streptococcal disease, the more I thought about the matter the more I realized that I could not do that without first dealing with transformation. Because, of course, it was Avery, MacLeod, and McCarty who published in 1944 the now classical and landmark paper which described the first demonstration that deoxyribonucleic acid, a major component of the chromosome, is the substance that transmits hereditary information. This observation was made in experiments which employed pneumococci that were transformed in the test tube from one type into another by a highly refined substance consisting of DNA. Avery and his associates had been working on transformation for nearly 10 years when McCarty joined the group, replacing Colin MacLeod. As Dubos has recently noted, "In some ways McCarty's role in the identification of the transforming substance can be compared to that played by Michael Heidelburger 20 years before in the demonstration that the specific soluble substances of pneumococcal capsules are complex polysaccharides. " Under the guidance of Avery, McCarty applied his chemical skills to the identification of the active principle. The outcome was the demonstration that the transforming activity resided in the fraction that consisted of DNA. This result was initially greeted with skepticism, as in fact was Avery's earlier report that polysaccharides were antigens. But in each case the work was on solid ground, and the chemistry was flawless. Avery, as always, had selected his associates with care. Now let me turn briefly to the next phase of Dr. McCarty's career. In 1948 he was given the responsibility for the Laboratory of Streptococcal Diseases. Mac himself must tell us some time why the switch from the pneumococcus to the streptococcus, but the reasons were probably of two sorts. First, and most important, the significance of transformation as a general biological phenomenon required additional evidence that this process occurred in other bacterial species. What better species to turn to than Vol. 55, No. 10, November 1979
902
R. M. KRAUSE~~~~~ KRAUSE
the streptococcus, possessing as it did antigens that had been so elegantly characterized by Rebecca Lancefield? And yet, I suspect the persistent mystery surrounding the pathogenesis of rheumatic fever was a second and perhaps in some ways the overriding reason to switch from pneumococci to streptococci. During much of his time since then he has ranged broadly over the streptococcal cell wall and prospected the surface topography and the geological formations that lie beneath. And while doing that he has kept an alert and quizzical eye for a clue that might bridge the gap between streptococcal biology and the pathogenesis of rheumatic fever. Mac brought to research on streptococci the same biochemical skill that he had employed on transformation. Soon we knew the chemical and immunological nature of several major cell-wall antigens as well as their arrangement. There was at that time no more elegant research in immunochemistry than his studies on the nature of the streptococcal polysaccharides. I first learned of Dr. McCarty's early success on the chemical dissection of the streptococcus from Al Stetson, who also had been one of Mac's young associates. At the time, Rammelkamp, Stetson, and I were studying an outbreak of nephritis at Bainbridge Naval Training Medical Center. One weekend Stetson returned to his old haunts in New York and came back full of enthusiasm. I remember his excitement even today. He reported "Mac is going great guns. And so he was. I think my desire to work with Mac took form on that day and was kindled by Al's enthusiasm. Mac at a later date rather thought he would like to have me join his group, but of course neither of us in the end really had much say about the matter. The final decision was made by Tom Rivers. I remember very well the day that Mac led me into River's office-both of us hat in hand to receive the verdict on whether I was or was not to be accepted at Rockefeller. After some discussion, and an admonition by Rivers that he preferred unmarried young doctors-an admonition which I have followed to this day-Rivers finally turned to Mac and said "McCarty, do you want him'?" Mac replied yes he did, and Rivers said "Well then you can have him' '-as if I were a sack of potatoes. And so began my association with Mac-one which included joint authorship of five papers on the nature of streptococcal polysaccharides. In a recent review article Dr. McCarty acknowledges at the onset that Bull. N.Y. Acad. Med.
ACADEMY MEDAL
-~~~~~~~CDM
903 U
our efforts on streptococcal microbiology have not yet defined a mechanism for the pathogenesis of rheumatic fever. And he goes on to say that it is instructive to explore the reasons for this failure. I agree with him on that but a survey of the failure does not reflect his generally optimistic curiosity. Nor does it reflect the new and unanticipated opportunities that arose from his research on streptococci and the streptococcal polysaccharides. Let me cite one such example. These versatile carbohydrate antigens are now widely employed to examine the processes that regulate and modulate the immune response and the genetic influences that amplify it. Not so long ago, one of our former colleagues, Klaus Eichmann, who, among many others, is engaged in this work, dallied for a short while with the use of artificial antigens such as DNP and NIP. But, if I may say so, that diversion was soon nipped in the bud! And with that pun-of low quality I 'm afraid-I come to my comments on Mac McCarty, for so many years my friend, as well as a friend to those of you who are here-a wise man and a fine physician, but one of rare good humor. How many times we laughed at those puns which just seemed to tumble out spontaneously and without contrivance. In the laboratory we all knew we were expected to work hard but somehow there was an unwritten rule that talking about that was a matter of poor taste. Science was fun and talk about hard work was out of place. I recall Mac's remark when several senior scientists, at a national meeting, were complaining about their technicians not working hard enough and not arriving at work on time. Mac cut that kind of conversation off in a hurry with the remark "All I ask is that they arrive in time for the morning coffee break. 'In short, he was not one to be occupied with trivial matters. Always thrifty in his lifestyle, he was equally thrifty in his use of words. He realized that a sparse use of words resulted in the clearest expression of any concept. His precise use of words grows out of his fascination with language, with its structure and texture, as illustrated by his mastery of at least the rudimentary elements of Farsi, the native language of Iran. He was the only one of a group of us who did so during a visit there. All of us who have worked with Mac were appalled at first by his fussiness over the construction of the written language. His own lean, almost hungry prose was hard for some of us to achieve. But out of the grueling process of drafting and redrafting a manuscript, which seemed to take forever, there emerged a document in which we can still take pride in Vol. 55, No. 10, November 1979
904
90
R. M. KRAUSE
authorship. In this connection let me mention here his vigorous editorial leadership of the Journal of Experimental Medicine for more than a decade. Dr. McCarty has been honored many times before and I am sure such honors will come to him again and again in the future. But now is the happy moment for a prize from his colleagues here in New York. The Academy Medal is bestowed upon him for his outstanding contributions to science and for his dedication to medicine and to a disease which remains a major cause of heart disease in the world today. Congratulations. I am proud to be a part of this ceremony.
Bull. N.Y. Acad. Med.
PRESENTATION OF THE ACADEMY MEDAL TO MACLYN McCARTY, M.D.* RICHARD M. KRAUSE, M.D. Director National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, Maryland is a personal joy to have been asked to pay tribute tonight to Maclyn McCarty, the 1979 recipient of the Academy Medal. I am one of a privileged group who has worked closely with Mac, and my purpose this evening is to describe briefly the man and his work. Mac is a son of the midwest, but it was first at Stanford University and later at Johns Hopkins University that he received the academic preparation on which his whole research career has been based. It is probably safe to say that his early schooling in the midwest had less influence, because at least one of his high school years was spent at Culver Military Academy, not especially noted as a campus where ideas flourish. But I suspect, Mac, that just enough of the military spit and polish you learned there was admired much later by Tom Rivers, then in the United States Navy as a commodore of the Rockefeller Institute Navy unit, a unit which you joined as a lieutenant, later rising to lieutenant commander. I have always wondered if your promotion to lieutenant commander was due in part, at least, to your early training at Culver! At Stanford Dr. McCarty was introduced to biochemistry. Later, at Hopkins, his preparation in this science extended beyond the usual medical curriculum. Throughout his career biochemistry has been on the cutting edge of his research. Yet, it must be added, his approach has never been just biochemical. It has always been tempered with a search for biological principles that in the end may have medical significance. He acquired this appreciation for the intricate nature of medical problems during three years of pediatric training at Harriet Lane. Then, after a year with Dr. Tillet at New York University, he arrived at Dr. O.T. Avery's laboratory at The Rockefeller Institute for Medical Research in 1941. There he rapidly rose through the ranks and was appointed member and physician in 1950. In
IT
*Presented at the Stated Meeting of the New York Academy of Medicine held April 19, 1979.
Vol. 55, No. 10, November 1979
900
KRAUSE R. M. KRAUSE
R. M.
900
NI .\(.I.)
I
N
M )
.
%. 1. 1).
,
Bull. N.Y. Acad. Med.
ACADEMY MEDAL
l~ ~~~~~~CDM
901 0
1960 he accepted responsibility for the leadership of the Hospital as physician-in-chief and later as vice-president, serving as an advisor and counselor to both Dr. Bronk and Dr. Seitz. It had been my initial intention to mention only in passing Dr. McCarty's research with Avery on the transformation of the pneumococcus. The story has been widely told recently-by Rene Dubos in his book on The Professor, the Institute and DNA and now most recently in The Ninth Day of Creation, by Horace Freeland Judson. And while I have, for personal reasons, a desire to focus especially on Dr. McCarty's work on streptococcal disease, the more I thought about the matter the more I realized that I could not do that without first dealing with transformation. Because, of course, it was Avery, MacLeod, and McCarty who published in 1944 the now classical and landmark paper which described the first demonstration that deoxyribonucleic acid, a major component of the chromosome, is the substance that transmits hereditary information. This observation was made in experiments which employed pneumococci that were transformed in the test tube from one type into another by a highly refined substance consisting of DNA. Avery and his associates had been working on transformation for nearly 10 years when McCarty joined the group, replacing Colin MacLeod. As Dubos has recently noted, "In some ways McCarty's role in the identification of the transforming substance can be compared to that played by Michael Heidelburger 20 years before in the demonstration that the specific soluble substances of pneumococcal capsules are complex polysaccharides. " Under the guidance of Avery, McCarty applied his chemical skills to the identification of the active principle. The outcome was the demonstration that the transforming activity resided in the fraction that consisted of DNA. This result was initially greeted with skepticism, as in fact was Avery's earlier report that polysaccharides were antigens. But in each case the work was on solid ground, and the chemistry was flawless. Avery, as always, had selected his associates with care. Now let me turn briefly to the next phase of Dr. McCarty's career. In 1948 he was given the responsibility for the Laboratory of Streptococcal Diseases. Mac himself must tell us some time why the switch from the pneumococcus to the streptococcus, but the reasons were probably of two sorts. First, and most important, the significance of transformation as a general biological phenomenon required additional evidence that this process occurred in other bacterial species. What better species to turn to than Vol. 55, No. 10, November 1979
902
R. M. KRAUSE~~~~~ KRAUSE
the streptococcus, possessing as it did antigens that had been so elegantly characterized by Rebecca Lancefield? And yet, I suspect the persistent mystery surrounding the pathogenesis of rheumatic fever was a second and perhaps in some ways the overriding reason to switch from pneumococci to streptococci. During much of his time since then he has ranged broadly over the streptococcal cell wall and prospected the surface topography and the geological formations that lie beneath. And while doing that he has kept an alert and quizzical eye for a clue that might bridge the gap between streptococcal biology and the pathogenesis of rheumatic fever. Mac brought to research on streptococci the same biochemical skill that he had employed on transformation. Soon we knew the chemical and immunological nature of several major cell-wall antigens as well as their arrangement. There was at that time no more elegant research in immunochemistry than his studies on the nature of the streptococcal polysaccharides. I first learned of Dr. McCarty's early success on the chemical dissection of the streptococcus from Al Stetson, who also had been one of Mac's young associates. At the time, Rammelkamp, Stetson, and I were studying an outbreak of nephritis at Bainbridge Naval Training Medical Center. One weekend Stetson returned to his old haunts in New York and came back full of enthusiasm. I remember his excitement even today. He reported "Mac is going great guns. And so he was. I think my desire to work with Mac took form on that day and was kindled by Al's enthusiasm. Mac at a later date rather thought he would like to have me join his group, but of course neither of us in the end really had much say about the matter. The final decision was made by Tom Rivers. I remember very well the day that Mac led me into River's office-both of us hat in hand to receive the verdict on whether I was or was not to be accepted at Rockefeller. After some discussion, and an admonition by Rivers that he preferred unmarried young doctors-an admonition which I have followed to this day-Rivers finally turned to Mac and said "McCarty, do you want him'?" Mac replied yes he did, and Rivers said "Well then you can have him' '-as if I were a sack of potatoes. And so began my association with Mac-one which included joint authorship of five papers on the nature of streptococcal polysaccharides. In a recent review article Dr. McCarty acknowledges at the onset that Bull. N.Y. Acad. Med.
ACADEMY MEDAL
-~~~~~~~CDM
903 U
our efforts on streptococcal microbiology have not yet defined a mechanism for the pathogenesis of rheumatic fever. And he goes on to say that it is instructive to explore the reasons for this failure. I agree with him on that but a survey of the failure does not reflect his generally optimistic curiosity. Nor does it reflect the new and unanticipated opportunities that arose from his research on streptococci and the streptococcal polysaccharides. Let me cite one such example. These versatile carbohydrate antigens are now widely employed to examine the processes that regulate and modulate the immune response and the genetic influences that amplify it. Not so long ago, one of our former colleagues, Klaus Eichmann, who, among many others, is engaged in this work, dallied for a short while with the use of artificial antigens such as DNP and NIP. But, if I may say so, that diversion was soon nipped in the bud! And with that pun-of low quality I 'm afraid-I come to my comments on Mac McCarty, for so many years my friend, as well as a friend to those of you who are here-a wise man and a fine physician, but one of rare good humor. How many times we laughed at those puns which just seemed to tumble out spontaneously and without contrivance. In the laboratory we all knew we were expected to work hard but somehow there was an unwritten rule that talking about that was a matter of poor taste. Science was fun and talk about hard work was out of place. I recall Mac's remark when several senior scientists, at a national meeting, were complaining about their technicians not working hard enough and not arriving at work on time. Mac cut that kind of conversation off in a hurry with the remark "All I ask is that they arrive in time for the morning coffee break. 'In short, he was not one to be occupied with trivial matters. Always thrifty in his lifestyle, he was equally thrifty in his use of words. He realized that a sparse use of words resulted in the clearest expression of any concept. His precise use of words grows out of his fascination with language, with its structure and texture, as illustrated by his mastery of at least the rudimentary elements of Farsi, the native language of Iran. He was the only one of a group of us who did so during a visit there. All of us who have worked with Mac were appalled at first by his fussiness over the construction of the written language. His own lean, almost hungry prose was hard for some of us to achieve. But out of the grueling process of drafting and redrafting a manuscript, which seemed to take forever, there emerged a document in which we can still take pride in Vol. 55, No. 10, November 1979
904
90
R. M. KRAUSE
authorship. In this connection let me mention here his vigorous editorial leadership of the Journal of Experimental Medicine for more than a decade. Dr. McCarty has been honored many times before and I am sure such honors will come to him again and again in the future. But now is the happy moment for a prize from his colleagues here in New York. The Academy Medal is bestowed upon him for his outstanding contributions to science and for his dedication to medicine and to a disease which remains a major cause of heart disease in the world today. Congratulations. I am proud to be a part of this ceremony.
Bull. N.Y. Acad. Med.
