Janet Rowley: Ground-breaking researcher who established that genetic mutations are the cause of cancer and not the result of it

Janet Rowley was a medical researcher whose innovative study of chromosomes led to a revolutionary understanding that certain forms of cancer are caused by genetic abnormalities.

Rowley, who was awarded the US’s highest civilian honour, the Presidential Medal of Freedom, in 2009, was a part-time researcher who often worked at her dining room table in the early years of her career. She made her first landmark discoveries in 1972, when she became the first scientist to find evidence that alterations in chromosomes could lead to forms of leukaemia and other former of cancer.

Some scientists were sceptical of her findings, and the New England Journal of Medicine refused to publish a paper of hers. But she was repeatedly able to demonstrate a link between genetic markers, or repeated chromosomal patterns, and particular diseases. Before her ground-breaking studies, most scientists believed that genetic mutations occurred after cancer invaded the body. Rowley established that the opposite was true: that genetic abnormalities were the cause of cancer, not the result of it. “Few would have thought this was possible,” the Director of the US National Institutes of Health, Francis Collins, said. “She was way ahead of the field on this.”

Before turning to lab work, Rowley had treated children with Downs syndrome and other developmental difficulties. In 1959 Downs syndrome was one of the first conditions associated with a chromosomal aberration. Rowley began her study of chromosomes in 1960 in England, where her husband, also a noted researcher, was on sabbatical. When she returned to Chicago in 1961 she persuaded a former teacher to let her work in his laboratory; she had just enough space for a microscope. She became adept at analysing chromosomes, photographing the chromosomes in her laboratory then arranging the images on her dining room table for further study. She warned her four sons not to move them out of sequence.

During a second tour of study in England in the early 1970s, Rowley learned a new technique called “banding,” the use of stains to observe and identify chromosomes with greater precision. This led to her first major discovery. In examining the chromosomes of a patient with acute myeloid leukemia, she noticed that part of chromosome 8 had broken off and swapped places with part of chromosome 21. She was the first to identify the phenomenon that became known as translocation.

Soon after, she solved the mystery of the “Philadelphia chromosome”, which had been an enigma in the field of genetics. In the early 1960s, two researchers in Philadelphia had identified a structural anomaly in chromosome 22 that seemed to be correlated with chronic myelogenous leukemia. But no one understood the full significance of the Philadelphia chromosome until Rowley realised that a portion had broken away and attached itself to chromosome 9. Through the process of translocation, part of chromosome 9 had, in turn, migrated to chromosome 22. “It was a very striking finding,” Harold Varmus, a Nobel laureate and the director of the National Cancer Institute, said. “Virtually every case of [myelogenous] leukemia had a Philadelphia chromosome.”

By the 1980s other scientists were using Rowley’s findings to analyse the components of cancer cells produced by abnormal genes. In 2001 the US Food and Drug Administration approved a drug, commercially known as Gleevec, that has proved effective in treating chronic myelogenous leukemia.

The incremental process – from initial observation to Rowley’s moment of discovery to the experiments that led to a form of therapy – has been cited as an example of the scientific method at its best. “You can draw a line from Janet’s research to the development of a drug to treat a specific leukemia,” said Collins, who has also directed the Human Genome Project. “The development of Gleevec is a remarkable advance toward making what had been a fatal disease something that can be treated more as a chronic condition. We’re all standing on the shoulders of Janet Rowley and others like her who proved that the paradigm worked.”

She was born in 1925 in New York and grew up mainly in Chicago. Her father worked in stores and later taught retail management while her mother was a primary school teacher.

Rowley was 15 when she entered an advanced programme at the University of Chicago; in 1944 she was accepted into the university’s medical school, but because of a quota that limited the number of women – only three in a class of 65 – she had to wait a year. She graduated from medical school in 1948, and a day later married Donald Rowley, a fellow medical student who later made important discoveries about the immune system and invented the gel electrode, a widely used tool to measure cardiac activity.

Since Rowley’s first discoveries, more than 70 diseases and disorders have been linked to genetic anomalies. Her laboratory, which focuses on leukaemia and lymphoma, has found more than a dozen of those connections. “I was 47 years old before I did anything that people would really look at twice,” she said. “Patience is an important aspect ... and good luck.”

After being forced to wait a year to enter medical school, Rowley became one of the first women to make major discoveries in a field dominated by men. “She probably mentored over 100 women in her career,” said Michelle Le Beau, who began working in Rowley’s laboratory in 1981 and is now director of the University of Chicago’s Comprehensive Cancer Center and its Cancer Cytognenetics Laboratory. “She showed women that you could have a professional life, you could have a personal life and you could have a family. I think, in that respect, she was a remarkable role model.”

Rowley continued to work at her laboratory until shortly before her death, riding her bicycle to work each day. Her colleagues expressed dismay that the biggest prize of all, the Nobel, never came her way.

Janet Davison, scientist: born New York 5 April 1925; married 1948 Donald Rowley (died 2013; three sons, and one son deceased); died Chicago 17 December 2017.

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