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Janet Davison Rowley
Jason Smith, courtesy of the University of Chicago
Obituary
Janet Davison Rowley Cytogeneticist who established that cancer is a genetic disease. Born in New York, NY, USA, on April 5, 1925, she died from complications of ovarian cancer in Chicago, IL, USA, on Dec 17, 2013, aged 88 years. In 1990 Janet Rowley described how 30 years previously, as a cytogeneticist working on leukaemia, she had “shared the frustration of my colleagues over our inability to define the chromosome changes in malignant cells with any certainty”. Were these changes a mere reflection of something more fundamental that was responsible for the malignancy? Or were they, as she suspected, its cause? Early in 1972 she found two patients with acute myeloid leukaemia who had the same reciprocal translocation in chromosomes 8 and 21. She might have disregarded the finding as no more than random, but she didn’t. Speculating that the translocation might be the cause of their disease she wrote a short report for The New England Journal of Medicine. It was rejected. “When I phoned to ask why”, she recalled, “I was told that in their judgement my paper was unimportant.” She resubmitted it to the French journal Annales de Génétique, which published it in 1973. But Rowley’s view of cancer as a genetic disease continued to be debated for the best part of another decade. In the end, of course, it prevailed. “Her work was the foundation for the genetic basis of cancer”, says Professor Michelle Le Beau, Director of the University of Chicago’s Cancer Cytogenetics Laboratory. Rowley had not anticipated a career in research. She had done a degree in philosophy before enrolling to study medicine at the University of Chicago—one of only three women in a class of 65. She graduated in 1948, married a 406
fellow student, and spent the next 20 years raising a family and working part time. One Chicago clinic at which she worked was for children with developmental disorders, says Professor Richard Larson, Director of the University of Chicago’s Hematologic Malignancies Clinical Research Program. “Some of them had Down’s syndrome and, as I understand, that started her thinking there might be a genetic basis not only for this but for other disorders.” Two even more seminal developments were the periods Rowley spent in Oxford with her immunologist husband Donald who was there on sabbatical. Rather than play the tourist she used the first stint, in 1961–62, to learn more of the new discipline of cytogenetics. On her return to the University of Chicago she became an assistant professor and set about studying the karyotypes of patients with leukaemia. In 1970, during her second visit to Oxford, she learned how to use new staining methods that revealed the characteristic banded appearance of chromosomes. “The development of banding techniques allowed Dr Rowley to recognise translocations”, says Larson. “With these techniques you could not only identify each chromosome but also the regions of each chromosome.” In a 1973 letter to Nature Rowley reported her observations on chromosomes 22 and 9 in nine patients with chronic myelogenous leukaemia (CML). A decade previously David Hungerford and Peter Nowell had shown that a loss of material from chromosome 22, the Philadelphia (Ph) chromosome as it had become known, was associated with CML. What Rowley had noticed was a length of extra material in chromosome 9 of each of these patients. “The amount of additional material”, she wrote, “is approximately equal to the amount missing from the Ph chromosome suggesting there may be a hitherto undetected translocation between the long arm of 22 and the long arm of 9.” So it proved. And as more evidence accumulated that patients with the same forms of leukaemia tended to have the same chromosomal abnormalities, so the case for cancer as a genetic disorder grew increasingly persuasive. “I think the discovery in 1973 of the translocations was really key”, says Le Beau, “because they formed probably the major class of genetic changes in leukaemia”. Rowley’s work paved the way for later developments including new drugs such as imatinib. As Blum-Riese Distinguished Service Professor of Medicine Rowley continued working at Chicago University almost until the end of her life. “She was very humble, particularly later in her career”, says Larson. With a Lasker Award and many other awards her reputation was established. “She was quick to recognise other people’s work, especially her trainees.” Much in demand as a mentor, “she had a passion for science that she passed on to all her trainees”, says Le Beau. Rowley’s husband died in 2013 and she is survived by three of their four sons.
Geoff Watts www.thelancet.com Vol 383 February 1, 2014
Obituary
Janet Davison Rowley Cytogeneticist who established that cancer is a genetic disease. Born in New York, NY, USA, on April 5, 1925, she died from complications of ovarian cancer in Chicago, IL, USA, on Dec 17, 2013, aged 88 years. In 1990 Janet Rowley described how 30 years previously, as a cytogeneticist working on leukaemia, she had “shared the frustration of my colleagues over our inability to define the chromosome changes in malignant cells with any certainty”. Were these changes a mere reflection of something more fundamental that was responsible for the malignancy? Or were they, as she suspected, its cause? Early in 1972 she found two patients with acute myeloid leukaemia who had the same reciprocal translocation in chromosomes 8 and 21. She might have disregarded the finding as no more than random, but she didn’t. Speculating that the translocation might be the cause of their disease she wrote a short report for The New England Journal of Medicine. It was rejected. “When I phoned to ask why”, she recalled, “I was told that in their judgement my paper was unimportant.” She resubmitted it to the French journal Annales de Génétique, which published it in 1973. But Rowley’s view of cancer as a genetic disease continued to be debated for the best part of another decade. In the end, of course, it prevailed. “Her work was the foundation for the genetic basis of cancer”, says Professor Michelle Le Beau, Director of the University of Chicago’s Cancer Cytogenetics Laboratory. Rowley had not anticipated a career in research. She had done a degree in philosophy before enrolling to study medicine at the University of Chicago—one of only three women in a class of 65. She graduated in 1948, married a 406
fellow student, and spent the next 20 years raising a family and working part time. One Chicago clinic at which she worked was for children with developmental disorders, says Professor Richard Larson, Director of the University of Chicago’s Hematologic Malignancies Clinical Research Program. “Some of them had Down’s syndrome and, as I understand, that started her thinking there might be a genetic basis not only for this but for other disorders.” Two even more seminal developments were the periods Rowley spent in Oxford with her immunologist husband Donald who was there on sabbatical. Rather than play the tourist she used the first stint, in 1961–62, to learn more of the new discipline of cytogenetics. On her return to the University of Chicago she became an assistant professor and set about studying the karyotypes of patients with leukaemia. In 1970, during her second visit to Oxford, she learned how to use new staining methods that revealed the characteristic banded appearance of chromosomes. “The development of banding techniques allowed Dr Rowley to recognise translocations”, says Larson. “With these techniques you could not only identify each chromosome but also the regions of each chromosome.” In a 1973 letter to Nature Rowley reported her observations on chromosomes 22 and 9 in nine patients with chronic myelogenous leukaemia (CML). A decade previously David Hungerford and Peter Nowell had shown that a loss of material from chromosome 22, the Philadelphia (Ph) chromosome as it had become known, was associated with CML. What Rowley had noticed was a length of extra material in chromosome 9 of each of these patients. “The amount of additional material”, she wrote, “is approximately equal to the amount missing from the Ph chromosome suggesting there may be a hitherto undetected translocation between the long arm of 22 and the long arm of 9.” So it proved. And as more evidence accumulated that patients with the same forms of leukaemia tended to have the same chromosomal abnormalities, so the case for cancer as a genetic disorder grew increasingly persuasive. “I think the discovery in 1973 of the translocations was really key”, says Le Beau, “because they formed probably the major class of genetic changes in leukaemia”. Rowley’s work paved the way for later developments including new drugs such as imatinib. As Blum-Riese Distinguished Service Professor of Medicine Rowley continued working at Chicago University almost until the end of her life. “She was very humble, particularly later in her career”, says Larson. With a Lasker Award and many other awards her reputation was established. “She was quick to recognise other people’s work, especially her trainees.” Much in demand as a mentor, “she had a passion for science that she passed on to all her trainees”, says Le Beau. Rowley’s husband died in 2013 and she is survived by three of their four sons.
Geoff Watts www.thelancet.com Vol 383 February 1, 2014