samedi 21 décembre 2013
Janet D. Rowley, Who Discovered Cancer Can Be Genetic, Dies at 88 – The New York Times on Friday, December 20th 2013 by By MARGALIT FOX
Dr. Janet D. Rowley, a physician who four decades ago became the first person to show a conclusive link between certain genetic abnormalities and certain cancers, died on Tuesday at her home in Chicago. She was 88.
The death, from complications of ovarian cancer, was announced by theUniversity of Chicago, where Dr. Rowley was the Blum-Riese distinguished service professor of medicine, molecular genetics and cell biology, and human genetics.
Dr. Rowley, described by The New York Times in 2011 as “the matriarch of modern cancer genetics,” made her pathbreaking discovery in 1972, when she found that a particular type of leukemia could result when two chromosomes abnormally exchanged genetic material.
Her findings helped establish cancer as a genetic disease. They also made possible the development of targeted drug therapies for specific cancers.
For her work, Dr. Rowley received the Lasker Award, given for distinguished contributions to medical science; the National Medal of Science from President Bill Clinton; and the Presidential Medal of Freedom from President Obama, among many other honors.
Janet Davison was born in New York City on April 5, 1925, and at 2 moved with her family to Chicago. At 15, she entered Hutchins College of the University of Chicago, which let gifted high school students start college.
After receiving her bachelor’s degree at 19, she was accepted to the university’s medical school but was told she would have to wait nine months to enroll: the school had already accepted its quota of women for the year — three in a class of 65.
She earned her M.D. from Chicago in 1948 and that year married a classmate, Dr. Donald Rowley. The mother of four young sons before long, she worked part time at a local clinic for children with Down syndrome.
The prospect of a research career, Dr. Rowley later said, did not occur to her.
“I actually thought I had it made working three days a week,” she said in a 2009 interview. “I could take care of my children, garden, weave and go to museums.”
Then, in 1961, Dr. Rowley joined her husband on a sabbatical year at Oxford University. Because Down syndrome was known to be caused by a chromosomal abnormality, she chose to spend her year there studying new methods of chromosome analysis.
Returning to Chicago, she begged the university for a room, a microscope and sufficient salary to pay a babysitter. The director of the laboratory that offered her space was an authority on leukemia, and Dr. Rowley began hunting for chromosomal anomalies in genetic samples from his patients.
While genetic abnormalities had long been known to cause other diseases, Dr. Rowley would be the first to show that they were also a cause — and not merely a consequence, as had been supposed — of cancer.
Her discovery took 10 years of peering through the microscope: at the time it was hard to tell chromosomes apart, even under magnification.
“This was less than a decade after Watson and Crick’s discovery,” Dr. Rowley told The Times in 2011, referring to James D. Watson and Francis Crick, the biologists who discovered the structure of DNA in 1953. “We were only beginning to have a notion of what DNA was like. There weren’t the right tools yet to stain it, cut it apart, examine and manipulate it.”
Dr. Rowley’s first significant advance came in 1970, on another sabbatical at Oxford. There she was introduced to a chemical staining technique, newly developed in Sweden, that made chromosomes appear striated and, as a result, easier to differentiate.
She stained and studied an array of chromosomes from patients with blood cancers, photographing the resulting images. Back in Chicago, she cut the photos into tiny fragments, with each fragment showing a chromosome in isolation — “paper dolls,” her children called them.
One day in 1972, Dr. Rowley cut up a sheaf of photos from a patient with acute myeloid leukemia, known as A.M.L. She laid the fragments out, chromosome by chromosome, on her dining table and ordered the children not to sneeze.
Aligned, the photos told a story of mutation. As Dr. Rowley noticed, two chromosomes had inappropriately swapped genetic material: a piece of chromosome 8 was now on chromosome 21, and vice versa. Examining photos from other A.M.L. patients, she saw that nearly every set showed the identical genetic swap.
Surely, she thought, other researchers had observed this before. She rushed to the library.
“They hadn’t,” Dr. Rowley told The Associated Press in 1988. “It was one of the greatest moments of my life.”
She soon identified another swap, between chromosomes 9 and 22, which resulted inchronic myelogenous leukemia, or C.M.L.
It was then so unorthodox to regard cancer as a genetic disease that “I got sort of amused tolerance at the beginning,” Dr. Rowley later said.
In 1977, she and her colleagues uncovered a third swap — between chromosomes 15 and 17 — which caused acute promyelocytic leukemia.
“That showed what we’d observed with the other two wasn’t an anomaly,” Dr. Rowley told The Times in 2011. “The third finding made me a believer.”
In chromosomes that had undergone the swaps — known in medical parlance as translocations — genes regulating processes like cell growth and cell division were no longer where they ought to be. As a result, cancer could arise.
Over the years, researchers have identified hundreds more translocations linked to specific cancers. The discoveries have given rise to drugs that target the genetic defects underpinning the cancers while sparing healthy cells.
Among the most successful of these drugs is Gleevec, used to treat C.M.L. Before its development, C.M.L. patients typically lived three to five years after diagnosis. Today, 90 percent are considered cured and have a normal life span.
Dr. Rowley’s husband, a noted pathologist at the University of Chicago, died this year; their eldest son, Donald, died in 1983. Survivors include three sons, David, Robert and Roger, and five grandchildren.
Her other awards include the Japan Prize and a lifetime achievement award from the American Association for Cancer Research. From 2002 to 2009, she served on President George W. Bush’s Council on Bioethics.
Despite her laurels, Dr. Rowley by all accounts remained almost preternaturally modest.
“People accuse me of being too humble,” she told The Times in 2011. “But looking down a microscope at banded chromosomes is not rocket science.”