- Email: [email protected]
Paul Emanuel Polani
Mary Seller
Obituary
Paul Emanuel Polani Genetics researcher and paediatrician who first described chromosomal abnormalities in Turner’s, Klinefelter’s, and Down’s syndromes and helped develop prenatal diagnostic testing. Born Jan 1, 1914, in Trieste, Italy; he died of leukaemia on Feb 18, 2006, in Guildford, Surrey, UK, aged 92 years. In the 1950s, when Paul Polani and Maurice Campbell were investigating congenital heart disease, Polani noticed that while coarctation of the aorta usually occurred only in men, women with Turner’s syndrome also frequently had coarctation. That suggested to him “that these females might be sex-reversed males”, he would later write, because he had found that their nuclei tested negative for chromatin, an indicator of the presence of a Y chromosome. In 1956, a paper on the frequency of red/green colour blindness had reported that men had only one X chromosome, suggesting that XO was the male phenotype. “But now I thought that Turner syndrome patients might be XO (45,X) females, rather than XY sex-reversed males, which suggested that, if XO, sex determination in Man (and perhaps in mammals generally) could not be as in Drosophila (where XOs are male)”, Polani would write. The idea that the Y chromosome was involved in sex determination was “very new in those days and almost heretical because Drosophila was considered the model for all mammals, and humans in particular”, said Francesco Giannelli, who worked with Polani from 1960 onward at the Paediatric Research Unit at Guy’s Hospital (now the Department of Medical and Molecular Genetics) in London, UK. Polani and Charles Ford, a cytogeneticist, would together 1138
confirm the hypothesis by studying the chromosomes of patients with Turner’s syndrome. Once the results were published, “He immediately became well known because of this kind of work”, said Matteo Adinolfi, who worked with him for many years at the unit. Polani and Ford would go on to show that patients with Klinefelter’s syndrome had an XXY genotype, and thus prove that the Y chromosome had a role in sex determination. They also worked on Down’s syndrome, and were able to show that trisomy 21 that caused the condition was the result of a translocation. The work on Down’s syndrome encouraged Polani to develop techniques for prenatal diagnosis, Giannelli said, and the unit was “one of the first places where genetic counselling and testing was done on a large basis not only in cytogenetics but on bone marrow”. “He had the foresight to see how important genetics and cytogenetics in particular was going to be in paediatrics and in the diagnosis of disease”, said Caroline Mackie Ogilvie, who now works at the unit. Polani’s report on Klinefelter’s syndrome with Ford included the finding that affected patients had two types of cells—one with a normal chromosome complement and one with the Klinefelter chromosome complement. “That was the first case of mosaicism reported in man”, Giannelli said, and because such mosaics sometimes had a milder phenotype in Down’s syndrome and Klinefelter’s syndrome, it led Polani to suggest that people in the laboratory try to create mosaics or chimeras in mice. Mary Seller, for example, went on to investigate congenital anaemia in mice in studies that would lay the groundwork for bone marrow transplants. Working with Polani was “very stimulating because obviously he thought very laterally”, Seller said. Later, Polani would become intensely interested in how defects in meiosis led to infertility. Polani graduated in medicine from the University of Pisa in 1938, and went to London in 1939 to pursue his studies. When World War II began that year, however, he became the doctor of a naval auxiliary ship that travelled to the Far East. By the time he returned to the UK, Italy was allied with Germany, so he was interned. But doctors were needed in London, so he was appointed to the Evelina Hospital for Sick Children where he would stay until 1948, when he was granted a paediatric research fellowship at Guy’s Hospital to work on clinical kernicterus after rhesus isoimmunisation. Polani’s work on genetics began in earnest in 1950 when he started frequenting L S Penrose’s laboratory, the Galton, at University College London. In 1958, Polani became director of the National Spastic Society’s Medical Research Unit. Funding from the Society made the founding of the Paediatric Research Unit at Guy’s possible in 1960, and Polani would lead the unit until his retirement in 1983. “He would always infuse you with enthusiasm” and had a sense of fun in terms of doing research, Giannelli said. Polani’s wife, Nina, died in 1999.
Ivan Oransky [email protected]
www.thelancet.com Vol 367 April 8, 2006
Obituary
Paul Emanuel Polani Genetics researcher and paediatrician who first described chromosomal abnormalities in Turner’s, Klinefelter’s, and Down’s syndromes and helped develop prenatal diagnostic testing. Born Jan 1, 1914, in Trieste, Italy; he died of leukaemia on Feb 18, 2006, in Guildford, Surrey, UK, aged 92 years. In the 1950s, when Paul Polani and Maurice Campbell were investigating congenital heart disease, Polani noticed that while coarctation of the aorta usually occurred only in men, women with Turner’s syndrome also frequently had coarctation. That suggested to him “that these females might be sex-reversed males”, he would later write, because he had found that their nuclei tested negative for chromatin, an indicator of the presence of a Y chromosome. In 1956, a paper on the frequency of red/green colour blindness had reported that men had only one X chromosome, suggesting that XO was the male phenotype. “But now I thought that Turner syndrome patients might be XO (45,X) females, rather than XY sex-reversed males, which suggested that, if XO, sex determination in Man (and perhaps in mammals generally) could not be as in Drosophila (where XOs are male)”, Polani would write. The idea that the Y chromosome was involved in sex determination was “very new in those days and almost heretical because Drosophila was considered the model for all mammals, and humans in particular”, said Francesco Giannelli, who worked with Polani from 1960 onward at the Paediatric Research Unit at Guy’s Hospital (now the Department of Medical and Molecular Genetics) in London, UK. Polani and Charles Ford, a cytogeneticist, would together 1138
confirm the hypothesis by studying the chromosomes of patients with Turner’s syndrome. Once the results were published, “He immediately became well known because of this kind of work”, said Matteo Adinolfi, who worked with him for many years at the unit. Polani and Ford would go on to show that patients with Klinefelter’s syndrome had an XXY genotype, and thus prove that the Y chromosome had a role in sex determination. They also worked on Down’s syndrome, and were able to show that trisomy 21 that caused the condition was the result of a translocation. The work on Down’s syndrome encouraged Polani to develop techniques for prenatal diagnosis, Giannelli said, and the unit was “one of the first places where genetic counselling and testing was done on a large basis not only in cytogenetics but on bone marrow”. “He had the foresight to see how important genetics and cytogenetics in particular was going to be in paediatrics and in the diagnosis of disease”, said Caroline Mackie Ogilvie, who now works at the unit. Polani’s report on Klinefelter’s syndrome with Ford included the finding that affected patients had two types of cells—one with a normal chromosome complement and one with the Klinefelter chromosome complement. “That was the first case of mosaicism reported in man”, Giannelli said, and because such mosaics sometimes had a milder phenotype in Down’s syndrome and Klinefelter’s syndrome, it led Polani to suggest that people in the laboratory try to create mosaics or chimeras in mice. Mary Seller, for example, went on to investigate congenital anaemia in mice in studies that would lay the groundwork for bone marrow transplants. Working with Polani was “very stimulating because obviously he thought very laterally”, Seller said. Later, Polani would become intensely interested in how defects in meiosis led to infertility. Polani graduated in medicine from the University of Pisa in 1938, and went to London in 1939 to pursue his studies. When World War II began that year, however, he became the doctor of a naval auxiliary ship that travelled to the Far East. By the time he returned to the UK, Italy was allied with Germany, so he was interned. But doctors were needed in London, so he was appointed to the Evelina Hospital for Sick Children where he would stay until 1948, when he was granted a paediatric research fellowship at Guy’s Hospital to work on clinical kernicterus after rhesus isoimmunisation. Polani’s work on genetics began in earnest in 1950 when he started frequenting L S Penrose’s laboratory, the Galton, at University College London. In 1958, Polani became director of the National Spastic Society’s Medical Research Unit. Funding from the Society made the founding of the Paediatric Research Unit at Guy’s possible in 1960, and Polani would lead the unit until his retirement in 1983. “He would always infuse you with enthusiasm” and had a sense of fun in terms of doing research, Giannelli said. Polani’s wife, Nina, died in 1999.
Ivan Oransky [email protected]
www.thelancet.com Vol 367 April 8, 2006