Janet Rowley (1925–2013) Geneticist Who Discovered That Broken Chromosomes Cause Cancer

COMMENT OBITUARY Janet Rowley (1925–2013) Geneticist who discovered that broken chromosomes cause cancer.

anet Rowley, the ‘matriarch of modern that she identified between chromosomes 8 the mechanism behind an effective drug: cancer genetics’, transformed our and 21 is now known to account for up to retinoic acid. A derivative of vitamin A, the Junderstanding of cancer. In the 1960s 12% of cases of acute myeloid leukaemia. drug restores normal function to its dis- she would cut out ‘paper dolls’ at the dining She published the work in a singly authored rupted protein receptor. room table — but not for her children to paper in June 1973 (J. D. Rowley Ann. Genet. For chronic myeloid leukaemia, a disease play with. These photographs of human 16, 109–112; 1973). The same month, she that was once a death sentence, Rowley’s dis- chromosomes eventually yielded discov- published a paper in Nature (J. D. Rowley covery enabled work that led to new, effec- eries that established the genetic basis of Nature 243, 290–293; 1973) that character- tive treatments including imatinib, approved cancer and led to targeted in the United States in 2001. cancer therapies. She received numerous pres- Janet Davison was born in tigious prizes for her research. New York City on 5 April 1925 I first met Janet in 2000, and spent most of her life in when the efficacy of imatinib Chicago, Illinois. Encour- was well known. Aged 75, aged by her mother, a high- instead of dwelling on her UNIV. CHICAGO MEDICINE CHICAGO UNIV. school teacher and librarian, seminal work on chronic Janet received her bachelor’s myeloid leukaemia, she told degree from the University me about new pathogenetic of Chicago at the age of 19. mechanisms of acute myeloid Accepted subsequently to the leukaemia that she was work- university’s medical school, ing on, and that she swam she had to wait nine months to regularly in Lake Michigan enrol because the school had and cycled to and from work. already reached its quota of Janet was also outspoken women: three in a class of 65. about her beliefs. Despite The day after her graduation serving on former US Presi- in 1948, she married a class- dent George W. Bush’s Coun- mate, Donald Rowley, who cil on Bioethics, she was highly later became a distinguished critical of the administration’s pathologist. policy that barred federal fund- In 1955, Janet began work- ing of embyronic stem-cell ing part-time in a local clinic, research. In 2009, she stood where she treated children with Down’s ized a genetic abnormality found in people next to President Barack Obama when he syndrome. The developmental disorder was with chronic myeloid leukaemia. lifted the ban. linked in 1959 to an extra copy of chromo- Rowley showed that the ‘Philadelphia In 2012, Janet, Nicholas Lydon and I some 21, and Rowley became fascinated with chromosome’, an aberrant version of chro- were awarded the Japan Prize for work that inherited genetic diseases. When her hus- mosome 22 (named after the city where led to imatinib. By the last evening of the band took a sabbatical in England in 1961, researchers identified the abnormality) week-long events surrounding the prize, she arranged to study with Laszlo Lajtha, a was a genetic swap: the truncated chromo- I was spent. Janet, 30 years my senior and haematologist at the Churchill Hospital in some 22 was accompanied by an elongated recovering from chemotherapy for ovarian Oxford. There, she began to examine chro- chromosome 9. Previously, a large genetic cancer, was still going strong. I asked her mosomes in the laboratory. deletion had been thought to be involved. In how she managed. With a twinkle in her Returning to the United States in 1962, 1977, she identified a third translocation, in eye, she replied that I had had to chase my she secured a job with Leon Jacobson, a people with acute promyelocytic leukaemia. three children around while she had been haematologist at the University of Chicago. Her work was met with a chorus of able to rest. Rowley asked for a darkroom, a microscope scepticism and wonder that anyone would That summed up Janet. She had incred- and a salary sufficient to pay a babysitter. bother to study chromosome abnormali- ible energy and curiosity and was gracious Over the next decade, she scoured cells ties, which were then considered to be an and humble, with the ability to make others from people with leukaemia, looking for effect of disease rather than a cause. By the around her feel good about themselves. ■ chromosomal abnormalities. 1980s, however, each of the abnormali- During a second sabbatical in Oxford, she ties had been molecularly characterized, Brian J. Druker is director of the Knight perfected techniques to stain chromosomes, revealing that translocations create ‘fusion’ Cancer Institute at Oregon Health & Science making it easier to identify them. She was proteins that drive cell growth. Since then, University, Portland, Oregon, and a Howard the first to realize that bits of chromosomes dozens of translocations have been found Hughes Medical Institute investigator. He in some human cancer cells had broken in other cancers. shared the 2012 Japan Prize with off and swapped places — a phenomenon For acute promyelocytic leukaemia, Janet Rowley and Nicholas Lydon. known as translocation. The translocation Rowley’s discovery helped to uncover e-mail: [email protected]