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Am J Hum Genet 28:101-106, 1976
E
THE WILLIAM ALLAN MEMORIAL AWARD Presented to Philip Levine and Alexander S. Wiener at the annual meeting of the American Society of Human Genetics Baltimore, Maryland October 10, 1975 CITATION
Philip Levine and Alexander S. Wiener have each accumulated an amazingly long and distinguished record of research achievement; their many fundamental contributions to our knowledge of human erythrocytic allotypes have had far-reaching effects in the advancement not only of human genetics but of immunohematology, physical anthropology, and forensic medicine. It is an honor to'be responsible for this citation of their illustrious careers on the occasion of their receiving the Allan Award of the American Society of Human Genetics. I have known both men for 28 years and have been a scientific collaborator with both, on separate occasions of course. In fact, only one other person ever published with both Levine and Wiener, and that was their beloved mentor, Karl Landsteiner. Although Levine and Wiener have been honored separately on numerous occasions, presentation of the Allan Award marks the seventh occasion that they have been honored jointly. I do not believe that any other independent scientists have been honored together so many times. Levine and Wiener received the Lasker Award in 1946, the Ward Burdick Award in 1946, the Passano Award in 1951, the Landsteiner Memorial Award in 1956, the Kennedy Award in 1966, and Fellowships in the Royal College of Physicians. Only the last were presented separately (Levine in 1973 and Wiener in 1974) perhaps because the English were fearful of direct confrontation between two strong personalities known to differ with one another. I have a photograph of Levine and Wiener on the wall of my office; the caption reads, "Dr. Levine chats with Dr. Wiener. They still dispute which one discovered the Rh factor." I could have better pictures of both men, but I like this caption because it neatly summarizes why Levine and Wiener have been jointly honored on so many occasions. Although Rh has linked the names of Levine and Wiener in the minds of both the scientific and lay communities, these two gentlemen are far from linked, either physically or intellectually. Only portions of their respective careers are similar. Neither Levine nor Wiener requires Rh priority to claim fame; their other research accomplishments are certainly more than sufficient. Levine was born in Russia in 1900 and at 8 years of age emigrated to the United States. Wiener, on the other hand, was born in 1907 in Brooklyn, New York. o 1976 by the American Society of Human Genetics. All rights reserved.
101
102
THE WILLIAM ALLAN MEMORIAL AWARD
Levine lost no time learning English and securing an education; although both men enjoyed equally rapid education and early research success, Levine was a world-famous scientist before Wiener graduated from medical school. Levine, coming from a very poor family, matriculated at City College of New York which was, and still is, tuition-free. He saw himself through Cornell Medical College by working every summer. He received a Soldiers and Sailors Memorial Scholarship after his second year which not only eased the financial burden for his last 2 years but allowed him to spend 2 postdoctoral years earning an M.A. degree in 1925. Although Levine received no academic honors, he was ultimately elected to the National Academy of Sciences. Wiener came from a middle class family; his father was an attorney. He graduated Phi Beta Kappa from Cornell in 1926, and Long Island College Hospital in 1930. When this medical school became Downstate Division of State University of New York, he was promptly elected to Alpha Omega Alpha. Both Levine and Wiener published scientifically before they graduated from medical school. Levine reported on a potentially dangerous type 0 universal donor [1]. This was the co-author, Jennie Mabee, a girl sitting next to him; her serum contained lysins for type A which were unusually potent. Indeed they must have
been, because Levine is subtype A2. Wiener published three reports: (1) a masterful study of 500 mother-baby pairs in which he showed that anti-A and anti-B in cord blood was dependent both on the mother having such antibodies and on the baby being ABO compatible with the mother [2]; and (2) a study on ABO typing, which he attributed to the ancient Chinese [3]. This, of course, was a dreadful mistake, but a very fortunate one for him. Karl Landsteiner saw this report and, through Levine, invited Wiener to Rockefeller Institute to discuss the matter. The result was a third report, a retraction [4], and the beginning of Wiener's long association with Landsteiner. The professional careers of Levine and Wiener are markedly different. Levine took his M.A. work under Arthur F. Coca, a pioneer in allergy research in America, and then joined Landsteiner at Rockefeller Institute where he worked from 1925 to 1932. During this period he became internationally known for the description of both the MN and the P blood types in 1927 [5, 6]. He spent 1932 to 1935 at the University of Wisconsin publishing over 20 reports on the effect of Salmonella serotypes on phage binding and action [7]. He returned to his family in New York in 1935 to work as transfusionist at the Beth Israel Hospital of Newark, New Jersey. In 1944 he joined the Ortho Pharmaceutical Company and established the Division of Immunohematology at the new Ortho Research Foundation. In my view, this division is the finest human red cell reference laboratory in existence. Wiener, lacking any options after medical school, began private practice in 1932. Although he is still a practicing physician in Brooklyn, his interests in blood typing, coupled with a lawyer-father, led him into forensic medicine. In 1938, he became serologist for the Chief Medical Examiner of the City of New York. He also joined New York University School of Medicine where he has been full pro-
THE WILLIAM ALLAN MEMORIAL AWARD
103
fessor since 1968. His forensic medicine laboratory is universally recognized as the most reliable in the entire world. Looking at Levine's accomplishments, we see not only M and N [5, 6] but the discovery of three other allelic blood types, Hr for Rh [8], k for K [9], and s for S [10]. Levine also discovered P (now P1) [6], Mia (Miltenberger) of the MN system [11], and Tja [12]; he defined LW [13] and did early definitive work on Dia (Diego) [14]. Tja is particularly interesting: T stands for tumor and j for the patient's name. This patient was Tj(a-), her serum contained anti-Tja, but her breast cancer tissue was actually Tj(a+) because it could adsorb her serum antibodies. This was the first "tumor antigen." Levine later suggested that Tj(a-) women had a strong tendency for repeated abortions [15], and showed Tja to be the common specificity for the cold-warm lysins of paroxysmal cold hemoglobinuria [16]. LW was Levine's efficient explanation of the rhesus-human crossreaction, a human red cell antigen inherited independently of Rh but which interacted with Rh to support the agglutination (and Rh polymorphism) described by Landsteiner and Wiener [13]. Levine described a new human allohemagglutinin in 1939 [17] which he found in the serum of a woman who, after delivering an erythroblastotic stillbirth, suffered a violent hemolytic reaction when she was given ABO compatible blood from her husband. These agglutinins were later seen to have the same specificity for human blood samples as the rabbit anti-rhesus agglutinins of Landsteiner and Wiener. Levine was able to connect the variables of this picture and, in 1941, published his pathogenesis of erythroblastosis [8], a monumental intellectual tour de force that greatly stimulated contemporary hematology. But Levine was not through with this problem, or with his capacity for synthesis; 2 years later he discerned the protective effect of parental ABO incompatibility on the occurrence of maternal Rh immunization [18]. Levine's work in 1932-1935 on Salmonella phage was also remarkable though unappreciated because the world was unprepared for such sophisticated analysis. He not only related phage binding to Salmonella serotypes, but showed that selected capsular polysaccharides effectively blocked such binding [7]. Levine's description of the polygenic basis for expression of the Bombay (Oh) blood type [19] played an important role in the interpretation of emerging data from analysis of human oligosaccharides carrying specific A, B, H, and Lewis antigen activity. He also described type A lacking H [20]. Levine only once described a complication in human blood typing, 87%o Rh (Rh'0 or CD) [8]. He did, however, describe three very rare Rh phenotypes, r'r' immunized to both D and c [21], ryrs [22], and rGrG [23]. The achievements of Wiener are totally different. Not once did he encounter an original allelic relationship between two antigens until he began his studies of simian allotypes in 1964. On the contrary, he began working with Landsteiner in the hope of developing more reliable tests for the MN types. It was while looking at rabbit anti-rhesus for M that he found human Rh polymorphism in 1937. These agglutination reactions, however, were too weak for Landsteiner's liking, and it
THE WILLIAM ALLAN MEMORIAL AWARD was not until H. R. Peters of Johns Hopkins sent blood specimens from three cases of hemolytic transfusion reaction that Landsteiner agreed to the importance of Rh. Thus, not only was Rh published in 1940 [24], but so was transfusion reaction due to Rh [25]. Wiener established 85%o Rh (Rho) in 1940 [24], but in 1941 he found 70%o Rh (rh') [26], and in 1943, 30%o Rh (rh") [27]. It is little wonder that the latter report was also his first on complex Rh alleles. And this was just in time because, in 1944 he described [28] weak Rh (later called W ho and DU). In 1957 Wiener described RhA [29], and 2 years later RhB [30], RhV [31], and RhD [32]. In 1960, I teased him by saying that he would have a hard time establishing RhE if it ever came along. But nothing new has come along, and Wiener may in fact have found all of the Rho-associated antigens. It is not surprising, therefore, *that Wiener has been such a strong proponent of multiple complex alleles. How could he be otherwise, considering what he personally found? Wiener described blocking Rh antibodies in 1944 [33], the first test for antibodies incapable of agglutinating red cells in saline. He showed the role of plasma proteins in support of Rh agglutination by IgG antibodies in 1945 [34], adding that these antibodies, rather than saline agglutinins, crossed the placenta. Wiener also discovered U of the MN system [35], I as the specificity of most cold agglutinins [36], and Me as a crossreaction between M and Henshaw [37]. He described Rh in nonhuman primates in 1953 [38] and, in more recent years, he has been responsible for exceptionally fine work on simian allotypes [39], a problem on which he is still actively engaged. Wiener's two other discoveries are remarkable examples of his virtuosity in serology. In 1951 [40], he measured the survival of maternal Rh antibodies in Rh-negative babies, and stated that the half-life was 30 days; we have no better value for IgG survival to this day. In 1953 [41], he estimated the relative antigen site densities of Rh, Kell, and Duffy; his ratio for Rh: Kell = 4.5 is in agreement with recent radioimmunoassay data. We have no independent measure of Duffy sites as yet. Clearly, Levine and Wiener are extraordinarily successful research workers. Although their individual accomplishments differ considerably, both must be considered outstanding products of Karl Landsteiner. Each, by his numerous discoveries concerning the inheritance of erythrocytic allotypes, contributed enormously to the advancement of human genetics. They are now honored accordingly with the Allan Award of the American Society of Human Genetics. I am delighted to have this opportunity to profess my sincere personal affection and admiration to both Philip Levine and Al Wiener, and to offer both the warm gratitude of the membership of the American Society of Human Genetics for their many years of productive research. (Richard E. Rosenfield) 104
REFERENCES 1. LEVINE P, MABEE J: A dangerous "universal donor" detected by direct matching of bloods. J Immunol 8:425-431, 1923 2. PoiAYEs SH, LEDERER M, WIENER AS: Studies on isohemagglutination. II. The Landsteiner blood groups in mothers and infants. J Immunol 17:545-554, 1929
THE WILLIAM ALLAN MEMORIAL AWARD
105
3. WIENER AS, LEDERER M, POLAYES SH: Studies in isohemagglutination. I. Theoretical considerations. J Immunol 16:469-482, 1929 4. WIENER AS, LEDERER M, POLAYES SH: A note on the paper, "Studies in isoagglutination." J Immunol 17:357-360, 1929 5. LANDSTEINER K, LEVINE P: A new agglutinable factor differentiating individual human bloods. Proc Soc Exp Biol Med 24:600-602, 1927 6. LANDSTEINER K, LEVINE P: Further observations on individual differences of human
blood. Proc Soc Exp Biol Med 24:941-942, 1927 7. LEVINE P, FRISCH AW: Specific inhibition of bacteriophage by bacterial extracts. Proc Soc Exp Biol Med 30:993-996, 1933 8. LEVINE P, BURNHAM L, KATZIN EM, VOGEL P: The role of isoimmunization in the pathogenesis of erythroblastosis fetalis. Am J Obstet Gynecol 42 :925-937, 1941 9. LEVINE P, BACKER M, WIGOD M, PONDER R: A new human hereditary blood property (Cellano) present in 99.8% of all bloods. Science 109:464-466, 1949 10. LEVINE P, KUHMICHEL AB, WIGOD M, KOCH E: A new blood factor, s, allelic to S. Proc Soc Exp Biol Med 78:218-220, 1951 11. LEVINE P, STOCK AH, KUHMICHEL AB, BRONIKOVSKY N: A new human blood factor of rare incidence in the general population. Proc Soc Exp Biol Med 77:402-403, 1951 12. LEVINE P, BOBBITT OB, WALLER RK, KUHMICHEL AB: Isoimmunization by a new blood factor in tumor cells. Proc Soc Exp Biol Med 77:403-405, 1951 13. LEVINE P, CELANO MJ, WALLACE J, SANGER R: A human "D-like" antibody. Nature 198:596-597, 1963 14. LEVINE P, ROBINSON EA, LAYRISSE M, ARENDS T, DOMINGUEZ SR: The Diego blood factor. Nature 177:40-41, 1956 15. LEVINE P, KOCH EA: The rare human isoagglutinin anti-Tja and habitual abortion. Science 120:239-241, 1954 16. LEVINE P, CELANO MJ, FALKOWSKI F: The specificity of the antibody in paroxysmal cold hemoglobinuria (P.C.H.). Transfusion 3:278-280, 1963 17. LEVINE P, STETSON RE: An unusual case of intra-group agglutination. J. Am Med Assoc 113:126-127, 1939 18. LEVINE P: Serological factors as possible causes in spontaneous abortion. J Hered 34:71-80, 1943 19. LEVINE P, ROBINSON EA, CELANO MJ, BRIGGS 0, FALKINBURG L: Gene interaction resulting in suppression of blood group substance B. Blood 10:1100-1108, 1955 20. LEVINE P, UHLIR M, WHITE J: Ah, incomplete suppression of A resembling Oh* VOX Sang 6:561-567, 1961 21. LEVINE P, COOPER MB, KOCH EA: A serologic and genetic analysis of an rYr' (dCe/dCe) patient producing anti-D and anti-c. Blood 9:817-823,1954 22. MCGEE R, LEVINE P, CELANO MJ: First example of genotype ryry: a family study. Science 125:1043, 1957 23. LEVINE P, ROSENFIELD RE, WHITE J: The first example of the Rh phenotype, rGrG. Am J Hum Genet 13 :299-305, 1961 24. LANDSTEINER K, WIENER AS: An agglutinable factor in human blood recognizable by immune sera for rhesus blood. Proc Soc Exp Biol Med 43 :223, 1940 25. WIENER AS, PETERS HR: Hemolytic reactions following transfusions of blood of the homologous group with three cases in which same agglutinogen was responsible. Ann Intern Med 13:2306-2322, 1940 26. WIENER AS: Hemolytic reactions following transfusions of blood of the homologous group. II. Further observations on the role of property Rh, particularly in cases without demonstrable isoantibodies. Arch Pathol 32:227-250, 1941 27. WIENER AS: Distribution and heredity of variants of the Rh type. Science 98:182184, 1943 28. WIENER AS: The Rh series of allelic genes. Science 100:595-597, 1944
106
THE WILLIAM ALLAN MEMORIAL AWARD
29. WIENER AS, GEIGER J, GORDON EB: Mosaic nature of the Rho factor of human blood. Exp Med Surg 15:75-82, 1957 30. UNGER LJ, WIENER AS, WEINER L: New antibody (anti-RhB) resulting from blood transfusion in an Rh-positive patient. J Am Med Assoc 170:1380-1383, 1959 31. UNGER LJ, WIENER AS: A "new" antibody, anti-Rhc, resulting from isosensitization by pregnancy with special reference to the heredity of a new Rh-Hr agglutinogen N h2e. J Lab Clin Med 54:835-842, 1959 32. SACKS MS, WIENER AS, JAHN EF, SPURLING CL, UNGER LJ: Isosensitization to a new blood factor, RhD, with special reference to its clinical importance. Ann Intern Med 51:740-747, 1959 33. WIENER AS: A new test (blocking test) for Rh sensitization. Proc Soc Exp Biol Med 56:173-176, 1944 34. WIENER AS: Conglutination test for Rh sensitization. .J Lab Clin Med 30:662-667, 1945. 35. WIENER AS, UNGER LJ, COHEN L: Distribution and heredity of blood factor U. Science 119:734-735, 1954 36. WIENER AS, UNGER LJ, COHEN L, FELDMAN J: Type-specific cold autoantibodies as a cause of acquired hemolytic anemia and transfusion reactions; biologic test with bovine red cells. Ann Intern Med 44:221-240, 1956 37. WIENER AS, ROSENFIELD RE: Me, a blood factor common to the antigenic properties M and He. J Immunol 87:376-378, 1961 38. WIENER AS: Blood group factors in anthropoid apes and monkeys. I. Studies on a chimpanzee, "Pan." Am J Phys Anthropol 10:372-375, 1952 39. MOOR-JANKOWSKI J, WIENER AS, ROGERS C: Blood groups of chimpanzees demonstrated with isoimmune serums. Science 145:1441-1443, 1964 40. WIENER AS: The half-life of passively acquired antibody globulin molecules in infants. J Exp Med 94:213-221, 1951 41. WIENER AS, GORDON EB: Quantitative test for antibody-globulin coating of human blood cells and its practical importance. Am J Clin Pathol 23 :429-446, 1953
First International Symposium on HLA and Disease The First International Symposium on HLA and Disease will be held on June 23-25, 1976 at Palais des Congres, Paris, France. Chairmen: J. Dausset and A. Svejgaard. For information contact Congres-Services, 1, rue Jules Lefebvre, 75009 Paris, France.
Am J Hum Genet 28:101-106, 1976
E
THE WILLIAM ALLAN MEMORIAL AWARD Presented to Philip Levine and Alexander S. Wiener at the annual meeting of the American Society of Human Genetics Baltimore, Maryland October 10, 1975 CITATION
Philip Levine and Alexander S. Wiener have each accumulated an amazingly long and distinguished record of research achievement; their many fundamental contributions to our knowledge of human erythrocytic allotypes have had far-reaching effects in the advancement not only of human genetics but of immunohematology, physical anthropology, and forensic medicine. It is an honor to'be responsible for this citation of their illustrious careers on the occasion of their receiving the Allan Award of the American Society of Human Genetics. I have known both men for 28 years and have been a scientific collaborator with both, on separate occasions of course. In fact, only one other person ever published with both Levine and Wiener, and that was their beloved mentor, Karl Landsteiner. Although Levine and Wiener have been honored separately on numerous occasions, presentation of the Allan Award marks the seventh occasion that they have been honored jointly. I do not believe that any other independent scientists have been honored together so many times. Levine and Wiener received the Lasker Award in 1946, the Ward Burdick Award in 1946, the Passano Award in 1951, the Landsteiner Memorial Award in 1956, the Kennedy Award in 1966, and Fellowships in the Royal College of Physicians. Only the last were presented separately (Levine in 1973 and Wiener in 1974) perhaps because the English were fearful of direct confrontation between two strong personalities known to differ with one another. I have a photograph of Levine and Wiener on the wall of my office; the caption reads, "Dr. Levine chats with Dr. Wiener. They still dispute which one discovered the Rh factor." I could have better pictures of both men, but I like this caption because it neatly summarizes why Levine and Wiener have been jointly honored on so many occasions. Although Rh has linked the names of Levine and Wiener in the minds of both the scientific and lay communities, these two gentlemen are far from linked, either physically or intellectually. Only portions of their respective careers are similar. Neither Levine nor Wiener requires Rh priority to claim fame; their other research accomplishments are certainly more than sufficient. Levine was born in Russia in 1900 and at 8 years of age emigrated to the United States. Wiener, on the other hand, was born in 1907 in Brooklyn, New York. o 1976 by the American Society of Human Genetics. All rights reserved.
101
102
THE WILLIAM ALLAN MEMORIAL AWARD
Levine lost no time learning English and securing an education; although both men enjoyed equally rapid education and early research success, Levine was a world-famous scientist before Wiener graduated from medical school. Levine, coming from a very poor family, matriculated at City College of New York which was, and still is, tuition-free. He saw himself through Cornell Medical College by working every summer. He received a Soldiers and Sailors Memorial Scholarship after his second year which not only eased the financial burden for his last 2 years but allowed him to spend 2 postdoctoral years earning an M.A. degree in 1925. Although Levine received no academic honors, he was ultimately elected to the National Academy of Sciences. Wiener came from a middle class family; his father was an attorney. He graduated Phi Beta Kappa from Cornell in 1926, and Long Island College Hospital in 1930. When this medical school became Downstate Division of State University of New York, he was promptly elected to Alpha Omega Alpha. Both Levine and Wiener published scientifically before they graduated from medical school. Levine reported on a potentially dangerous type 0 universal donor [1]. This was the co-author, Jennie Mabee, a girl sitting next to him; her serum contained lysins for type A which were unusually potent. Indeed they must have
been, because Levine is subtype A2. Wiener published three reports: (1) a masterful study of 500 mother-baby pairs in which he showed that anti-A and anti-B in cord blood was dependent both on the mother having such antibodies and on the baby being ABO compatible with the mother [2]; and (2) a study on ABO typing, which he attributed to the ancient Chinese [3]. This, of course, was a dreadful mistake, but a very fortunate one for him. Karl Landsteiner saw this report and, through Levine, invited Wiener to Rockefeller Institute to discuss the matter. The result was a third report, a retraction [4], and the beginning of Wiener's long association with Landsteiner. The professional careers of Levine and Wiener are markedly different. Levine took his M.A. work under Arthur F. Coca, a pioneer in allergy research in America, and then joined Landsteiner at Rockefeller Institute where he worked from 1925 to 1932. During this period he became internationally known for the description of both the MN and the P blood types in 1927 [5, 6]. He spent 1932 to 1935 at the University of Wisconsin publishing over 20 reports on the effect of Salmonella serotypes on phage binding and action [7]. He returned to his family in New York in 1935 to work as transfusionist at the Beth Israel Hospital of Newark, New Jersey. In 1944 he joined the Ortho Pharmaceutical Company and established the Division of Immunohematology at the new Ortho Research Foundation. In my view, this division is the finest human red cell reference laboratory in existence. Wiener, lacking any options after medical school, began private practice in 1932. Although he is still a practicing physician in Brooklyn, his interests in blood typing, coupled with a lawyer-father, led him into forensic medicine. In 1938, he became serologist for the Chief Medical Examiner of the City of New York. He also joined New York University School of Medicine where he has been full pro-
THE WILLIAM ALLAN MEMORIAL AWARD
103
fessor since 1968. His forensic medicine laboratory is universally recognized as the most reliable in the entire world. Looking at Levine's accomplishments, we see not only M and N [5, 6] but the discovery of three other allelic blood types, Hr for Rh [8], k for K [9], and s for S [10]. Levine also discovered P (now P1) [6], Mia (Miltenberger) of the MN system [11], and Tja [12]; he defined LW [13] and did early definitive work on Dia (Diego) [14]. Tja is particularly interesting: T stands for tumor and j for the patient's name. This patient was Tj(a-), her serum contained anti-Tja, but her breast cancer tissue was actually Tj(a+) because it could adsorb her serum antibodies. This was the first "tumor antigen." Levine later suggested that Tj(a-) women had a strong tendency for repeated abortions [15], and showed Tja to be the common specificity for the cold-warm lysins of paroxysmal cold hemoglobinuria [16]. LW was Levine's efficient explanation of the rhesus-human crossreaction, a human red cell antigen inherited independently of Rh but which interacted with Rh to support the agglutination (and Rh polymorphism) described by Landsteiner and Wiener [13]. Levine described a new human allohemagglutinin in 1939 [17] which he found in the serum of a woman who, after delivering an erythroblastotic stillbirth, suffered a violent hemolytic reaction when she was given ABO compatible blood from her husband. These agglutinins were later seen to have the same specificity for human blood samples as the rabbit anti-rhesus agglutinins of Landsteiner and Wiener. Levine was able to connect the variables of this picture and, in 1941, published his pathogenesis of erythroblastosis [8], a monumental intellectual tour de force that greatly stimulated contemporary hematology. But Levine was not through with this problem, or with his capacity for synthesis; 2 years later he discerned the protective effect of parental ABO incompatibility on the occurrence of maternal Rh immunization [18]. Levine's work in 1932-1935 on Salmonella phage was also remarkable though unappreciated because the world was unprepared for such sophisticated analysis. He not only related phage binding to Salmonella serotypes, but showed that selected capsular polysaccharides effectively blocked such binding [7]. Levine's description of the polygenic basis for expression of the Bombay (Oh) blood type [19] played an important role in the interpretation of emerging data from analysis of human oligosaccharides carrying specific A, B, H, and Lewis antigen activity. He also described type A lacking H [20]. Levine only once described a complication in human blood typing, 87%o Rh (Rh'0 or CD) [8]. He did, however, describe three very rare Rh phenotypes, r'r' immunized to both D and c [21], ryrs [22], and rGrG [23]. The achievements of Wiener are totally different. Not once did he encounter an original allelic relationship between two antigens until he began his studies of simian allotypes in 1964. On the contrary, he began working with Landsteiner in the hope of developing more reliable tests for the MN types. It was while looking at rabbit anti-rhesus for M that he found human Rh polymorphism in 1937. These agglutination reactions, however, were too weak for Landsteiner's liking, and it
THE WILLIAM ALLAN MEMORIAL AWARD was not until H. R. Peters of Johns Hopkins sent blood specimens from three cases of hemolytic transfusion reaction that Landsteiner agreed to the importance of Rh. Thus, not only was Rh published in 1940 [24], but so was transfusion reaction due to Rh [25]. Wiener established 85%o Rh (Rho) in 1940 [24], but in 1941 he found 70%o Rh (rh') [26], and in 1943, 30%o Rh (rh") [27]. It is little wonder that the latter report was also his first on complex Rh alleles. And this was just in time because, in 1944 he described [28] weak Rh (later called W ho and DU). In 1957 Wiener described RhA [29], and 2 years later RhB [30], RhV [31], and RhD [32]. In 1960, I teased him by saying that he would have a hard time establishing RhE if it ever came along. But nothing new has come along, and Wiener may in fact have found all of the Rho-associated antigens. It is not surprising, therefore, *that Wiener has been such a strong proponent of multiple complex alleles. How could he be otherwise, considering what he personally found? Wiener described blocking Rh antibodies in 1944 [33], the first test for antibodies incapable of agglutinating red cells in saline. He showed the role of plasma proteins in support of Rh agglutination by IgG antibodies in 1945 [34], adding that these antibodies, rather than saline agglutinins, crossed the placenta. Wiener also discovered U of the MN system [35], I as the specificity of most cold agglutinins [36], and Me as a crossreaction between M and Henshaw [37]. He described Rh in nonhuman primates in 1953 [38] and, in more recent years, he has been responsible for exceptionally fine work on simian allotypes [39], a problem on which he is still actively engaged. Wiener's two other discoveries are remarkable examples of his virtuosity in serology. In 1951 [40], he measured the survival of maternal Rh antibodies in Rh-negative babies, and stated that the half-life was 30 days; we have no better value for IgG survival to this day. In 1953 [41], he estimated the relative antigen site densities of Rh, Kell, and Duffy; his ratio for Rh: Kell = 4.5 is in agreement with recent radioimmunoassay data. We have no independent measure of Duffy sites as yet. Clearly, Levine and Wiener are extraordinarily successful research workers. Although their individual accomplishments differ considerably, both must be considered outstanding products of Karl Landsteiner. Each, by his numerous discoveries concerning the inheritance of erythrocytic allotypes, contributed enormously to the advancement of human genetics. They are now honored accordingly with the Allan Award of the American Society of Human Genetics. I am delighted to have this opportunity to profess my sincere personal affection and admiration to both Philip Levine and Al Wiener, and to offer both the warm gratitude of the membership of the American Society of Human Genetics for their many years of productive research. (Richard E. Rosenfield) 104
REFERENCES 1. LEVINE P, MABEE J: A dangerous "universal donor" detected by direct matching of bloods. J Immunol 8:425-431, 1923 2. PoiAYEs SH, LEDERER M, WIENER AS: Studies on isohemagglutination. II. The Landsteiner blood groups in mothers and infants. J Immunol 17:545-554, 1929
THE WILLIAM ALLAN MEMORIAL AWARD
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3. WIENER AS, LEDERER M, POLAYES SH: Studies in isohemagglutination. I. Theoretical considerations. J Immunol 16:469-482, 1929 4. WIENER AS, LEDERER M, POLAYES SH: A note on the paper, "Studies in isoagglutination." J Immunol 17:357-360, 1929 5. LANDSTEINER K, LEVINE P: A new agglutinable factor differentiating individual human bloods. Proc Soc Exp Biol Med 24:600-602, 1927 6. LANDSTEINER K, LEVINE P: Further observations on individual differences of human
blood. Proc Soc Exp Biol Med 24:941-942, 1927 7. LEVINE P, FRISCH AW: Specific inhibition of bacteriophage by bacterial extracts. Proc Soc Exp Biol Med 30:993-996, 1933 8. LEVINE P, BURNHAM L, KATZIN EM, VOGEL P: The role of isoimmunization in the pathogenesis of erythroblastosis fetalis. Am J Obstet Gynecol 42 :925-937, 1941 9. LEVINE P, BACKER M, WIGOD M, PONDER R: A new human hereditary blood property (Cellano) present in 99.8% of all bloods. Science 109:464-466, 1949 10. LEVINE P, KUHMICHEL AB, WIGOD M, KOCH E: A new blood factor, s, allelic to S. Proc Soc Exp Biol Med 78:218-220, 1951 11. LEVINE P, STOCK AH, KUHMICHEL AB, BRONIKOVSKY N: A new human blood factor of rare incidence in the general population. Proc Soc Exp Biol Med 77:402-403, 1951 12. LEVINE P, BOBBITT OB, WALLER RK, KUHMICHEL AB: Isoimmunization by a new blood factor in tumor cells. Proc Soc Exp Biol Med 77:403-405, 1951 13. LEVINE P, CELANO MJ, WALLACE J, SANGER R: A human "D-like" antibody. Nature 198:596-597, 1963 14. LEVINE P, ROBINSON EA, LAYRISSE M, ARENDS T, DOMINGUEZ SR: The Diego blood factor. Nature 177:40-41, 1956 15. LEVINE P, KOCH EA: The rare human isoagglutinin anti-Tja and habitual abortion. Science 120:239-241, 1954 16. LEVINE P, CELANO MJ, FALKOWSKI F: The specificity of the antibody in paroxysmal cold hemoglobinuria (P.C.H.). Transfusion 3:278-280, 1963 17. LEVINE P, STETSON RE: An unusual case of intra-group agglutination. J. Am Med Assoc 113:126-127, 1939 18. LEVINE P: Serological factors as possible causes in spontaneous abortion. J Hered 34:71-80, 1943 19. LEVINE P, ROBINSON EA, CELANO MJ, BRIGGS 0, FALKINBURG L: Gene interaction resulting in suppression of blood group substance B. Blood 10:1100-1108, 1955 20. LEVINE P, UHLIR M, WHITE J: Ah, incomplete suppression of A resembling Oh* VOX Sang 6:561-567, 1961 21. LEVINE P, COOPER MB, KOCH EA: A serologic and genetic analysis of an rYr' (dCe/dCe) patient producing anti-D and anti-c. Blood 9:817-823,1954 22. MCGEE R, LEVINE P, CELANO MJ: First example of genotype ryry: a family study. Science 125:1043, 1957 23. LEVINE P, ROSENFIELD RE, WHITE J: The first example of the Rh phenotype, rGrG. Am J Hum Genet 13 :299-305, 1961 24. LANDSTEINER K, WIENER AS: An agglutinable factor in human blood recognizable by immune sera for rhesus blood. Proc Soc Exp Biol Med 43 :223, 1940 25. WIENER AS, PETERS HR: Hemolytic reactions following transfusions of blood of the homologous group with three cases in which same agglutinogen was responsible. Ann Intern Med 13:2306-2322, 1940 26. WIENER AS: Hemolytic reactions following transfusions of blood of the homologous group. II. Further observations on the role of property Rh, particularly in cases without demonstrable isoantibodies. Arch Pathol 32:227-250, 1941 27. WIENER AS: Distribution and heredity of variants of the Rh type. Science 98:182184, 1943 28. WIENER AS: The Rh series of allelic genes. Science 100:595-597, 1944
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29. WIENER AS, GEIGER J, GORDON EB: Mosaic nature of the Rho factor of human blood. Exp Med Surg 15:75-82, 1957 30. UNGER LJ, WIENER AS, WEINER L: New antibody (anti-RhB) resulting from blood transfusion in an Rh-positive patient. J Am Med Assoc 170:1380-1383, 1959 31. UNGER LJ, WIENER AS: A "new" antibody, anti-Rhc, resulting from isosensitization by pregnancy with special reference to the heredity of a new Rh-Hr agglutinogen N h2e. J Lab Clin Med 54:835-842, 1959 32. SACKS MS, WIENER AS, JAHN EF, SPURLING CL, UNGER LJ: Isosensitization to a new blood factor, RhD, with special reference to its clinical importance. Ann Intern Med 51:740-747, 1959 33. WIENER AS: A new test (blocking test) for Rh sensitization. Proc Soc Exp Biol Med 56:173-176, 1944 34. WIENER AS: Conglutination test for Rh sensitization. .J Lab Clin Med 30:662-667, 1945. 35. WIENER AS, UNGER LJ, COHEN L: Distribution and heredity of blood factor U. Science 119:734-735, 1954 36. WIENER AS, UNGER LJ, COHEN L, FELDMAN J: Type-specific cold autoantibodies as a cause of acquired hemolytic anemia and transfusion reactions; biologic test with bovine red cells. Ann Intern Med 44:221-240, 1956 37. WIENER AS, ROSENFIELD RE: Me, a blood factor common to the antigenic properties M and He. J Immunol 87:376-378, 1961 38. WIENER AS: Blood group factors in anthropoid apes and monkeys. I. Studies on a chimpanzee, "Pan." Am J Phys Anthropol 10:372-375, 1952 39. MOOR-JANKOWSKI J, WIENER AS, ROGERS C: Blood groups of chimpanzees demonstrated with isoimmune serums. Science 145:1441-1443, 1964 40. WIENER AS: The half-life of passively acquired antibody globulin molecules in infants. J Exp Med 94:213-221, 1951 41. WIENER AS, GORDON EB: Quantitative test for antibody-globulin coating of human blood cells and its practical importance. Am J Clin Pathol 23 :429-446, 1953
First International Symposium on HLA and Disease The First International Symposium on HLA and Disease will be held on June 23-25, 1976 at Palais des Congres, Paris, France. Chairmen: J. Dausset and A. Svejgaard. For information contact Congres-Services, 1, rue Jules Lefebvre, 75009 Paris, France.
