Am J Hum Genet 27:135-139, 1975
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THE WILLIAM ALLAN MEMORIAL AWARD Presented to Curt Stern at the annual meeting of the American Society of Human Genetics Portland, Oregon October 17, 1974 CITATION
The presentation of the Allan Award of this Society and the presidential address are the formal high spots of our meeting. But whereas the presidential address has been from the first what presidential addresses have to be, the Allan Award has gone in many directions-sometimes a recognition of distinguished human geneticists from abroad, and sometimes a recognition of mature members of this Society. Today our award is directed towards a very special example of the latter. Professor Curt Stern was born in Hamburg, Germany, on August 30, 1902. Twenty-one years later he received his Ph.D. from the University of Berlin-in protozoology, a student of Hartmann. In his presidential address to the 8th International Congress of Genetics in 1973, Dr. Stern gave such a charming account of how he entered the field of genetics that at the risk of boring those of you who heard him, I repeat it here. The year is now 1924. News of the excitement in the fly room at Columbia University, spreading throughout the scientific world, had reached the Kaiser Wilhelm Institute fur Biologie, where Stern was now a very, very new "assistent." One day Richard Goldschmidt, then director, recently armed with funding from the International Education Board, called Stern in. He came to the point quickly, for he was a busy Herr Doktor Geheimrat Professor: "Herr Stern, would you like a fellowship to study genetics with Morgan?" As Stern tells the story, he stood there for what seemed ages before he could think of a single word: "Jaaaaa." All of us struggling with the administrative complexities of modern science can but contemplate bemusedly this simpler era, when a director with insight could, without applying for funds, appointing a search committee, or passing out applications, simply tap the right man for an opportunity. Although Stern by this time had developed a keen interest in genetics, I wonder if any committee today would dare award such a fellowship to an individual apparently so poorly qualified. It is a frustrating challenge to attempt in these brief remarks to summarize the many facets in the career that exploded forthwith some 50 years ago. Let us begin with Stern the experimental geneticist. With all due respect to the out© 1975 by the American Society of Human Genetics. All rights reserved.
135
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THE WILLIAM ALLAN MEMORIAL AWARD
standing laboratories from whence the discoveries of the postwar years have issued, I wonder if there has ever been a more charged intellectual atmosphere than the fly room at Columbia in the 1920s. In 1924 our little star moved right in. At that time the precise relationship of genes to chromosomes was still being debated. The recognition of X-linked inheritance in Drosophila by Morgan in 1910 was a major step in establishing the chromosomal theory of inheritance, in that certain genes were inherited in a fashion which found its most logical explanation if they were located on the X chromosome. However, there was one well known inherited trait in Drosophila-bobbed bristles-which, although clearly related to sex, did not follow the rules of X linkage. Stern's first major contribution to genetics was the demonstration that the puzzling behavior of this trait could best be explained if the responsible gene resided on the Y chromosome [1]. The fact that the unusual transmission of bobbed in certain stocks, from male to male, exactly paralleled the transmission of the Y chromosome was powerful evidence in support of the still controversial chromosomal theory of inheritance. Although this was not the first demonstration of Y-linked inheritance (reviewed in Stern [2]), it was certainly the most elegant. One of Stern's then puzzling observations was that by adding supernumerary Y chromosomes carrying the bobbed allele to the genome, one could obtain a normal phenotype. Some 40 years later, with the hypothesis that the bobbed series of alleles is responsible for varying deficiencies in the production of ribosomal RNA, this seminal observation on the additivity of action of these "deficiency" genes was again in the forefront, but now in the world of molecular genetics. We can skip over a series of solid but lesser contributions until 1931, when he struck another mighty blow for the chromosomal theory of inheritance. By an ingenious combination of cytology and genetics, he demonstrated that the genetic phenomenon of crossing over was accompanied by a physical exchange of segments between chromosomes [3], a demonstration still in every rigorous textbook dealing with classical genetics, even though, as he has reminded me, the "copy-
choice" (as opposed to "breakage-fusion") interpretation was not considered at that time. These early contributions played a major role in establishing the chromosomal theory of inheritance. We obviously cannot tarry for a complete review of Stern's Drosophila days, but three other studies are still required reading for students of the contributions of Drosophila to genetic theory: (1) the monumental paper in 1936 on somatic cell crossing over in Drosophila [4]; (2) his ingenious studies on the mechanism of gene action through the production of aneuploids carrying various combinations of a fourth chromosome mutant and its normal allele, with the concept of isoalleles [5]; and (3) his extensive use of genetic mosaics to dissect the genetic control of development in Drosophila (summary in Stern [6]). During World War II, as one aspect of a large biomedical research program on radiation effects at the University of Rochester in connection with the development of atomic weapons, Stern directed a research program which extended studies of the genetic effects of radiation on Drosophila down to much lower levels than
THE WILLIAM ALLAN MEMORIAL AWARD
137
previous studies-doses of 25 R and 50 R. And when the results of later experiments did not appear to agree in important respects with those conducted earlier, he stuck with the laborious study until he was able to write with assurance: "Viewing all experiments together, it appears that radiation at low dosages, administered at low intensity, induces mutation in Drosophila sperm. There is no threshold below which radiation fails to induce mutations" [7]. This statement is a cornerstone of radiation genetics. He put this background in radiation genetics to very good use as a member of the advisory committee to the Division of Biology and Medicine of the Atomic Energy Commission from 1950 to 1955, when important research policies were being developed. We turn now to Stern the human geneticist. His first contribution to human genetics was a paper coauthored with Don Charles in 1945 [8], pointing out how diseases due to maternal-fetal antigenic incompatibility, such as Rh disease, should be less frequent in consanguineous marriages-to my knowledge the first kind thing any geneticist ever said about consanguineous marriage-and a phenomenon whose importance is still unassessed. Since then, two of his chief interests in human genetics have been the inheritance of skin color in Negro-Caucasian crosses and aspects of sex-linked inheritance. With respect to the former, his is the demonstration that the optimum fit to the data is provided by the hypothesis that three or four pairs of segregating alleles with additive effects are involved [9, 10]. With respect to the latter, I refer you to his presidential address to this Society in 1957 entitled "On Porcupine Skin and Hairy Ears; or, The Alleged Sins of the Y Chromosome" [2]. With characteristic modesty, in that address he passes over his own classical work on bobbed bristles-which may have conditioned his life-long interest in this topic-in a single sentence. We come next to Stern the teacher. In this capacity we know him best for The Principles of Human Genetics, first published in 1949 and now in its third edition. Twenty-five years and 56,665 copies later, no other text has had a comparable impact on the field. It was my incredible privilege to be present at the conception if not the gestation and birth of the book, the former as usual undoubtedly a more lighthearted affair than the latter. The year was 1939, the place the University of Rochester, and Stern, who six years earlier had left Germany, undertook to lead a small group of graduate students in a seminar on human genetics at the University of Rochester. He spent a month assembling the literature he felt appropriate to review. I have brought here tonight the slim result -our bibliography for that seminar, some 110 titles, the germ of the text-to-be. Some of you might like to examine this later, and then ponder the changes 35 years have wrought. Incidentally, considering the times and the circumstances under which Stern left Germany, it would have been understandable if we had spent some time dissecting the monstrous perversion of genetic concepts then current in Germany. It is a measure of the man that not only did he consider this inappropriate in a seminar devoted to science, but although I recall some discussion of events in Nazi Germany, I cannot recall a single bitter diatribe concerning these events.
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THE WILLIAM ALLAN MEMORIAL AWARD
The clarity of exposition which made that book so outstanding has throughout his life been exceeded only by his oral presentations. Those of you who never heard Stern speak need not take my word for it-we have the evidence. You all know the book, but how many of you are familiar with his 12 half-hour films on genetics made in 1961 in connection with a major venture in film education sponsored by the American Institute of Biological Sciences and distributed all over the world. Herewith a 5-min excerpt from the film "Inheritance in Man." (Film clip) For those of you who still struggle, as I do, with the best way to present Rh disease to students, how about that? There have been at least three major "retirement parties" for Dr. Stern in recent years, in the course of which it has been established that there are some 50 persons proud to call themselves his students, either in the more formal sense or because of postdoctoral associations of one kind or another. We his students have had very different scientific experiences with Stern, depending on the nature of his work as we passed through his laboratory. But one experience we have all shared has been the exposure to a gentle but uncompromising perceptiveness which, even when drawing attention to some less than brilliant act on our part, somehow left us reassured there was still hope we would make it someday. During my first year of graduate work with Stern I did some incredibly stupid thing. I do not remember what it was, but it would be impossible to forget how Stern handled it. Having straightened me out, he paused a minute. I was waiting for the next blow to fall when he smiled and said, "You know, Jim, in Germany we have a proverb-great men make great mistakes." The application of this amazing quality was not restricted to his graduate students-how many nervous young scientists delivering an almost-first paper have had their day made by the right comment from Stern. And this is the appropriate place to mention Mrs. Stern-ever ready to extend the gracious hospitality of their home to occasions we remember as well as the classroom, interested and even apparently fascinated through thousands and thousands of conversations about genetics. Tucked away among the scientific papers are several essays on the nature of man and science, some directed essentially at lay audiences, which present the issues of scientific life with charm and feeling, and permit us to talk about Stern the philosopher of science. Someday go back and read "The Journey, Not the Goal" [11], published in 1944, with the thoughtful plea for a "wider and deeper realization of the value of science as an expression of a detached essence of human existence." Or read again "Thoughts on Research" [12], published in 1965, which I interpret as a Stern rebuke to little minds so obsessed by their own discoveries they fail utterly to appreciate the patient efforts of those who keep the system going-like chancellors. Read "Genes and People" [13], delivered in 1966 as a special lecture for laymen, in connection with the 3d International Congress of Human Genetics. It is pure delight to see the most recent developments in human genetics presented with a complete absence of scientific gobbledegook. And if you still have a little time, consult "Genetic Mosaics and Other Essays" [14] based on the Prather Lectures delivered in 1965 at Harvard.
THE WILLIAM ALLAN MEMORIAL AWARD
139
Finally, Stern the involved scientist and recognized leader. He is a past president of the Genetics Society of America, the American Society of Naturalists, and, of course, our own Society. He served as president of the 8th International Congress of Genetics last year. He has been elected to the American Philosophical Society, the American Academy of Arts and Sciences, and the National Academy of Sciences, from which he received the Kimber Genetics Medal in 1963. He has served as editor of the journal Genetics. A full list of his honors and of the important committees to which he has given so generously of his time would require several pages-enough has been said. Dr. Stern, in accepting the Allan Award for 1974 you honor the American Society of Human Genetics. (James V. Neel) REFERENCES 1. STERN C: Vererbung im Y-Chromosom von Drosophila melanogaster. Biol Zentralbl 46:344-348, 1926 2. STERN C: The problem of complete Y-linkage in man. Am J Hum Genet 9:147-166, 1957 3. STERN C: Zytologisch-genetische Untersuchungen als Beweise fur die Morgansche Theorie des Faktorenaustauschs. Biol Zentralbl 51:547-587, 1931 4. STERN C: Somatic crossing over and segregation in Drosophila melanogaster. Genetics 21:625-730, 1936 5. STERN C: Genic action as studied by means of the effects of different doses and combinations of alleles. Genetics 28:441-475, 1943 6. STERN C: Gene expression in genetic mosaics. Genetics 61, suppl.: 199-212, 1969 7. UPHOFF D, STERN C: The genetic effects of low intensity irradiation. Science 109:609-610, 1949 8. STERN C, CHARLES DR: The Rhesus gene and the effect of consanguinity. Science 101:305-307, 1945 9. STERN C: Model estimates of the frequency of white and near-white segregants in the American Negro. Acta Genet Statist Med (Basel) 4:281-298, 1953 10. STERN C: Model estimates of the number of gene pairs involved in pigmentation variability of the Negro-American. Hum Hered 20:165-168, 1970 11. STERN C: The journey, not the goal. Sci Mon 58:96-100, 1944 12. STERN C: Thoughts on research. Science 148:772-773, 1965 13. STERN C: Genes and people, in Proceedings 3d International Congress of Human Genetics, edited by CROW JE, NEEL JV, Baltimore, Johns Hopkins Press, 1967, pp 507-520 14. STERN C: Genetic Mosaics and Other Essays. Cambridge, Mass., Harvard Univ. Press, 1968
Xo
O: V.i
L.
-
;
THE WILLIAM ALLAN MEMORIAL AWARD Presented to Curt Stern at the annual meeting of the American Society of Human Genetics Portland, Oregon October 17, 1974 CITATION
The presentation of the Allan Award of this Society and the presidential address are the formal high spots of our meeting. But whereas the presidential address has been from the first what presidential addresses have to be, the Allan Award has gone in many directions-sometimes a recognition of distinguished human geneticists from abroad, and sometimes a recognition of mature members of this Society. Today our award is directed towards a very special example of the latter. Professor Curt Stern was born in Hamburg, Germany, on August 30, 1902. Twenty-one years later he received his Ph.D. from the University of Berlin-in protozoology, a student of Hartmann. In his presidential address to the 8th International Congress of Genetics in 1973, Dr. Stern gave such a charming account of how he entered the field of genetics that at the risk of boring those of you who heard him, I repeat it here. The year is now 1924. News of the excitement in the fly room at Columbia University, spreading throughout the scientific world, had reached the Kaiser Wilhelm Institute fur Biologie, where Stern was now a very, very new "assistent." One day Richard Goldschmidt, then director, recently armed with funding from the International Education Board, called Stern in. He came to the point quickly, for he was a busy Herr Doktor Geheimrat Professor: "Herr Stern, would you like a fellowship to study genetics with Morgan?" As Stern tells the story, he stood there for what seemed ages before he could think of a single word: "Jaaaaa." All of us struggling with the administrative complexities of modern science can but contemplate bemusedly this simpler era, when a director with insight could, without applying for funds, appointing a search committee, or passing out applications, simply tap the right man for an opportunity. Although Stern by this time had developed a keen interest in genetics, I wonder if any committee today would dare award such a fellowship to an individual apparently so poorly qualified. It is a frustrating challenge to attempt in these brief remarks to summarize the many facets in the career that exploded forthwith some 50 years ago. Let us begin with Stern the experimental geneticist. With all due respect to the out© 1975 by the American Society of Human Genetics. All rights reserved.
135
136
THE WILLIAM ALLAN MEMORIAL AWARD
standing laboratories from whence the discoveries of the postwar years have issued, I wonder if there has ever been a more charged intellectual atmosphere than the fly room at Columbia in the 1920s. In 1924 our little star moved right in. At that time the precise relationship of genes to chromosomes was still being debated. The recognition of X-linked inheritance in Drosophila by Morgan in 1910 was a major step in establishing the chromosomal theory of inheritance, in that certain genes were inherited in a fashion which found its most logical explanation if they were located on the X chromosome. However, there was one well known inherited trait in Drosophila-bobbed bristles-which, although clearly related to sex, did not follow the rules of X linkage. Stern's first major contribution to genetics was the demonstration that the puzzling behavior of this trait could best be explained if the responsible gene resided on the Y chromosome [1]. The fact that the unusual transmission of bobbed in certain stocks, from male to male, exactly paralleled the transmission of the Y chromosome was powerful evidence in support of the still controversial chromosomal theory of inheritance. Although this was not the first demonstration of Y-linked inheritance (reviewed in Stern [2]), it was certainly the most elegant. One of Stern's then puzzling observations was that by adding supernumerary Y chromosomes carrying the bobbed allele to the genome, one could obtain a normal phenotype. Some 40 years later, with the hypothesis that the bobbed series of alleles is responsible for varying deficiencies in the production of ribosomal RNA, this seminal observation on the additivity of action of these "deficiency" genes was again in the forefront, but now in the world of molecular genetics. We can skip over a series of solid but lesser contributions until 1931, when he struck another mighty blow for the chromosomal theory of inheritance. By an ingenious combination of cytology and genetics, he demonstrated that the genetic phenomenon of crossing over was accompanied by a physical exchange of segments between chromosomes [3], a demonstration still in every rigorous textbook dealing with classical genetics, even though, as he has reminded me, the "copy-
choice" (as opposed to "breakage-fusion") interpretation was not considered at that time. These early contributions played a major role in establishing the chromosomal theory of inheritance. We obviously cannot tarry for a complete review of Stern's Drosophila days, but three other studies are still required reading for students of the contributions of Drosophila to genetic theory: (1) the monumental paper in 1936 on somatic cell crossing over in Drosophila [4]; (2) his ingenious studies on the mechanism of gene action through the production of aneuploids carrying various combinations of a fourth chromosome mutant and its normal allele, with the concept of isoalleles [5]; and (3) his extensive use of genetic mosaics to dissect the genetic control of development in Drosophila (summary in Stern [6]). During World War II, as one aspect of a large biomedical research program on radiation effects at the University of Rochester in connection with the development of atomic weapons, Stern directed a research program which extended studies of the genetic effects of radiation on Drosophila down to much lower levels than
THE WILLIAM ALLAN MEMORIAL AWARD
137
previous studies-doses of 25 R and 50 R. And when the results of later experiments did not appear to agree in important respects with those conducted earlier, he stuck with the laborious study until he was able to write with assurance: "Viewing all experiments together, it appears that radiation at low dosages, administered at low intensity, induces mutation in Drosophila sperm. There is no threshold below which radiation fails to induce mutations" [7]. This statement is a cornerstone of radiation genetics. He put this background in radiation genetics to very good use as a member of the advisory committee to the Division of Biology and Medicine of the Atomic Energy Commission from 1950 to 1955, when important research policies were being developed. We turn now to Stern the human geneticist. His first contribution to human genetics was a paper coauthored with Don Charles in 1945 [8], pointing out how diseases due to maternal-fetal antigenic incompatibility, such as Rh disease, should be less frequent in consanguineous marriages-to my knowledge the first kind thing any geneticist ever said about consanguineous marriage-and a phenomenon whose importance is still unassessed. Since then, two of his chief interests in human genetics have been the inheritance of skin color in Negro-Caucasian crosses and aspects of sex-linked inheritance. With respect to the former, his is the demonstration that the optimum fit to the data is provided by the hypothesis that three or four pairs of segregating alleles with additive effects are involved [9, 10]. With respect to the latter, I refer you to his presidential address to this Society in 1957 entitled "On Porcupine Skin and Hairy Ears; or, The Alleged Sins of the Y Chromosome" [2]. With characteristic modesty, in that address he passes over his own classical work on bobbed bristles-which may have conditioned his life-long interest in this topic-in a single sentence. We come next to Stern the teacher. In this capacity we know him best for The Principles of Human Genetics, first published in 1949 and now in its third edition. Twenty-five years and 56,665 copies later, no other text has had a comparable impact on the field. It was my incredible privilege to be present at the conception if not the gestation and birth of the book, the former as usual undoubtedly a more lighthearted affair than the latter. The year was 1939, the place the University of Rochester, and Stern, who six years earlier had left Germany, undertook to lead a small group of graduate students in a seminar on human genetics at the University of Rochester. He spent a month assembling the literature he felt appropriate to review. I have brought here tonight the slim result -our bibliography for that seminar, some 110 titles, the germ of the text-to-be. Some of you might like to examine this later, and then ponder the changes 35 years have wrought. Incidentally, considering the times and the circumstances under which Stern left Germany, it would have been understandable if we had spent some time dissecting the monstrous perversion of genetic concepts then current in Germany. It is a measure of the man that not only did he consider this inappropriate in a seminar devoted to science, but although I recall some discussion of events in Nazi Germany, I cannot recall a single bitter diatribe concerning these events.
138
THE WILLIAM ALLAN MEMORIAL AWARD
The clarity of exposition which made that book so outstanding has throughout his life been exceeded only by his oral presentations. Those of you who never heard Stern speak need not take my word for it-we have the evidence. You all know the book, but how many of you are familiar with his 12 half-hour films on genetics made in 1961 in connection with a major venture in film education sponsored by the American Institute of Biological Sciences and distributed all over the world. Herewith a 5-min excerpt from the film "Inheritance in Man." (Film clip) For those of you who still struggle, as I do, with the best way to present Rh disease to students, how about that? There have been at least three major "retirement parties" for Dr. Stern in recent years, in the course of which it has been established that there are some 50 persons proud to call themselves his students, either in the more formal sense or because of postdoctoral associations of one kind or another. We his students have had very different scientific experiences with Stern, depending on the nature of his work as we passed through his laboratory. But one experience we have all shared has been the exposure to a gentle but uncompromising perceptiveness which, even when drawing attention to some less than brilliant act on our part, somehow left us reassured there was still hope we would make it someday. During my first year of graduate work with Stern I did some incredibly stupid thing. I do not remember what it was, but it would be impossible to forget how Stern handled it. Having straightened me out, he paused a minute. I was waiting for the next blow to fall when he smiled and said, "You know, Jim, in Germany we have a proverb-great men make great mistakes." The application of this amazing quality was not restricted to his graduate students-how many nervous young scientists delivering an almost-first paper have had their day made by the right comment from Stern. And this is the appropriate place to mention Mrs. Stern-ever ready to extend the gracious hospitality of their home to occasions we remember as well as the classroom, interested and even apparently fascinated through thousands and thousands of conversations about genetics. Tucked away among the scientific papers are several essays on the nature of man and science, some directed essentially at lay audiences, which present the issues of scientific life with charm and feeling, and permit us to talk about Stern the philosopher of science. Someday go back and read "The Journey, Not the Goal" [11], published in 1944, with the thoughtful plea for a "wider and deeper realization of the value of science as an expression of a detached essence of human existence." Or read again "Thoughts on Research" [12], published in 1965, which I interpret as a Stern rebuke to little minds so obsessed by their own discoveries they fail utterly to appreciate the patient efforts of those who keep the system going-like chancellors. Read "Genes and People" [13], delivered in 1966 as a special lecture for laymen, in connection with the 3d International Congress of Human Genetics. It is pure delight to see the most recent developments in human genetics presented with a complete absence of scientific gobbledegook. And if you still have a little time, consult "Genetic Mosaics and Other Essays" [14] based on the Prather Lectures delivered in 1965 at Harvard.
THE WILLIAM ALLAN MEMORIAL AWARD
139
Finally, Stern the involved scientist and recognized leader. He is a past president of the Genetics Society of America, the American Society of Naturalists, and, of course, our own Society. He served as president of the 8th International Congress of Genetics last year. He has been elected to the American Philosophical Society, the American Academy of Arts and Sciences, and the National Academy of Sciences, from which he received the Kimber Genetics Medal in 1963. He has served as editor of the journal Genetics. A full list of his honors and of the important committees to which he has given so generously of his time would require several pages-enough has been said. Dr. Stern, in accepting the Allan Award for 1974 you honor the American Society of Human Genetics. (James V. Neel) REFERENCES 1. STERN C: Vererbung im Y-Chromosom von Drosophila melanogaster. Biol Zentralbl 46:344-348, 1926 2. STERN C: The problem of complete Y-linkage in man. Am J Hum Genet 9:147-166, 1957 3. STERN C: Zytologisch-genetische Untersuchungen als Beweise fur die Morgansche Theorie des Faktorenaustauschs. Biol Zentralbl 51:547-587, 1931 4. STERN C: Somatic crossing over and segregation in Drosophila melanogaster. Genetics 21:625-730, 1936 5. STERN C: Genic action as studied by means of the effects of different doses and combinations of alleles. Genetics 28:441-475, 1943 6. STERN C: Gene expression in genetic mosaics. Genetics 61, suppl.: 199-212, 1969 7. UPHOFF D, STERN C: The genetic effects of low intensity irradiation. Science 109:609-610, 1949 8. STERN C, CHARLES DR: The Rhesus gene and the effect of consanguinity. Science 101:305-307, 1945 9. STERN C: Model estimates of the frequency of white and near-white segregants in the American Negro. Acta Genet Statist Med (Basel) 4:281-298, 1953 10. STERN C: Model estimates of the number of gene pairs involved in pigmentation variability of the Negro-American. Hum Hered 20:165-168, 1970 11. STERN C: The journey, not the goal. Sci Mon 58:96-100, 1944 12. STERN C: Thoughts on research. Science 148:772-773, 1965 13. STERN C: Genes and people, in Proceedings 3d International Congress of Human Genetics, edited by CROW JE, NEEL JV, Baltimore, Johns Hopkins Press, 1967, pp 507-520 14. STERN C: Genetic Mosaics and Other Essays. Cambridge, Mass., Harvard Univ. Press, 1968
