This article was previously published in the 1998 Annual Report for the University of Chicago Medical Center.
“She was always after my blood,” recalls Claire Wright. “And she was welcome to it, but at that time it was the one thing I didn’t have much of to give.”
A nursery school teacher, Wright first realized she was short of blood on December 4, 1984. For several weeks she had felt sluggish: “Not just a little lethargic but tired, really tired. No amount of sleep would help.” Plus, she seemed to have bruises all over her legs and arms. “It’s normal for a nursery teacher to bump into things,” she said. Sometimes you have to move pretty fast and everything -- desks, chairs, tables, toys -- is at knee level. But it seemed like “all of a sudden I had a lot of bruises, more than usual, big ones that didn’t go away.”
That morning she felt worse than ever. The five-block walk from her home on Harper to the school on Woodlawn was a struggle. Then around 10 o’clock she started bleeding from a small cut that wouldn’t stop oozing. She went home and called her husband, Ben, a professor in the education department. He drove her to the hospital, where she was seen immediately by Dr. Thomas Jones, head of the general medicine clinic and a neighbor. He lived a few houses down on Harper.
Diagnosis took Jones less than five minutes. The exhaustion, the bruises, now the bleeding: “Claire,” he said, after checking her vital signs, “you have no blood.” Pathologists quickly confirmed his suspicion that she had leukemia and Wright was wheeled straight from the clinic to the sixth floor of the newly opened Mitchell Hospital. Still tired, profoundly anemic and now worried that at 57 she had a disease that to the best of her knowledge was generally fatal, she latched onto the only positive thing she could think of. “At least,” she remembers thinking as she was helped into her hospital bed, finally allowed to doze off, “at least, I don’t have to buy anybody a Christmas present.” Before long, a nurse came by to draw more precious blood.
No other hospital would have requested so much. Some of her blood went to the clinical laboratories for routine testing. But a little extra went to a chromosome research lab run by Dr. Janet Rowley, who was refining and testing an unusual theory. Scientists had long been aware of the extensive chromosomal abnormalities generally found in cancer cells. Sometimes these cells had double, even triple the number of chromosomes expected in normal cells. Somehow, they suspected, the uncontrolled division of cancer cells had disrupted the mechanisms that ordinarily regulate chromosome copying, resulting in profound disruption of this usually precise process.
But Rowley had a different theory. She suspected that tiny, quite subtle alterations of the chromosomes were driving the early stages of the disease, rather than the disease causing mounting but irrelevant chromosome damage. She had been looking for these subtle early signs since 1972, about a decade after her mentor, hematologist Leon Jacobson, had offered her a little lab space and a microscope. He and colleague Clifford Gurney had suggested that she look at chromosomes in cells from patients with leukemia and preleukemia. By 1984, when Claire got sick, Rowley had gathered considerable evidence that these early genetic changes were very specific -- that each type of leukemia, for instance, often had its own specific chromosomal abnormality. If she could figure out the connections between the chromosomes and the diseases, and convince her peers, it would radically change the way scientists thought about, and treated cancer.
Rowley and Wright were connected by more than a few test tubes of blood, however. They were nearly the same age. Rowley was born in 1925 and Wright two years later, in 1927, the year the University of Chicago Hospital opened. Both women got married in 1948 to men who earned advanced degrees from the University of Chicago and eventually won faculty appointments. Both had four children, settled in Hyde Park and devoted their lives to their families. They had even met occasionally, at faculty events or their children’s school.
By the late 1960s, with all eight children in school, both women were eager to take on new responsibilities. Wright became an assistant teacher at the Laboratory Schools, then returned to school to get an early childhood education degree and became a head nursery school teacher. Thirty years later -- after launching the educations of more than 300 three and four year olds -- she’s still teaching.
Rowley, meanwhile, had never entirely quit working. A whiz kid, who entered the University through the “Four-Year College in 1940 at the age of 15, she graduated from medical school -- one of six women in her class -- on December 17, 1948, at the age of 23. She married fellow medical student Donald Rowley (MD ‘50) the next day. They completed their internships by 1951. Although Janet received her medical license in 1951, she chose to spend the next 24 years working only two or three days a week, devoting most of her time to her children.
So it was only fitting that she made her first big discovery at home. After a sabbatical in Oxford in 1970-71 spent learning the latest staining techniques for illuminating the different stripes or “bands” on chromosomes, Rowley began to photograph the chromosomes of leukemia patients using the fluorescence microscope and she would take the pictures home to ponder. Her children often teased her about her jigsaw puzzles as she sat at their dining-room table, cutting each chromosome out of the photographs and carefully arranging them in pairs. A decade earlier, using standard techniques, two Philadelphia scientists had discovered that in patients with one particular type of leukemia, known as chronic myelogenous leukemia (CML), part of chromosome 22 seemed to be missing -- a phenomenon that quickly became known as the “Philadelphia chromosome.”
But late one afternoon in early 1972, while sorting out her photos of chromosomes, Rowley noticed something else. The chromosomes of a patient with acute myelogenous leukemia (AML) had two abnormalities. Instead of losing a piece, chromosomes 8 and 21 appeared to have made a trade; part of 21 had broken off and moved to chromosome 8, and part of 8 had moved to chromosome 21 -- an exchange that was called a “translocation.” When she looked again at other patients with this same kind of AML, she often saw the same process, sometimes with chromosomes 8 and 21 and sometimes involving two other chromosomes.
When Rowley began to look at the chromosomes of patients with CML, she found a slightly different version. The end of chromosome 22 wasn’t missing; it had been exchanged for a piece of chromosome 9. Lost in Philadelphia, this cancer-causing chromosome piece had finally been found in Chicago. Because of this transfer from one chromosome to another, important genes that regulated cell growth and division were no longer located in their normal position. The result was the uncontrolled cell growth of cancer.
Rowley and her colleagues subsequently identified several other chromosome translocations that were characteristic of specific malignancies, including a gene involved in most infant leukemias. Other scientists, from around the world, have used the translocations as road maps to narrow the search for different genes that were disrupted by chromosome damage, thus beginning the current era of cancer genetics -- an approach that promises to dominate the field for the coming decades.
Back in 1984, however, when Claire Wright got so sick, most scientists had only recently been convinced of the importance of translocations. The cancer clinicians were just beginning to investigate how this new information could improve treatment. “We’re still figuring out the clinical applications that have flowed from Janet’s discoveries,” said Richard Larson, MD, Rowley’s colleague and Wright’s doctor, “but one of the first things we learned was the importance of looking for certain chromosomal markers, like the 8;21 translocation that Claire had, as a guide to therapy. She was part of a clinical trial at the time, but we now know we did the right thing. More than 70 percent of patients with her disease and that particular chromosomal abnormality, which is found only five percent of the time, will respond well to the type of chemotherapy she received.”
In fact, Wright went into a lasting remission after her first course of induction chemotherapy. Because no one expected that to last, she had four more treatments. None was easy. Each time she spent weeks in the hospital recovering. Her husband moved into her room, a constant companion and vigilant guardian. “Larson was really on the ball and took care of my cancer,” recalls Wright. His colleague, Stephanie Williams, “was a pal,” said Wright. “She took care of me.” And John Ultmann, director of the Cancer Research Center at the time, “took care of Ben, always dropping by with articles for him to read, keeping him posted on the latest information.”
After six month of treatment, usually a couple weeks in the hospital followed by a few more weeks at home to recover -- a process that involved numerous crises, loads of discomfort and more than 100 blood transfusions -- therapy was finally over. In that six months “Ben’s hair had turned white,” laughs Wright, but that summer hers grew back in dark and curly. Oddly enough, she recalls, “I’ve been much healthier since I had chemotherapy. I had felt funny for a long time before I got really sick. Even in pictures taken a year or more before my diagnosis, I always looked a little off. I’ve felt much better ever since.”
“Nevertheless”, she adds, “I wouldn’t recommend it.”
The years have also been good to Rowley, bringing growing recognition for the importance of her ongoing discoveries. She has won most of the major prizes and honors in her field, including two big ones last fall: the coveted Lasker Award in September, often referred to as “America’s Nobels,” and in December the National Medal of Science, the nation's highest scientific honor. "Although I try not to take most of these things too seriously," she noted, "this is quite exciting. I couldn't sleep the night after I was told of the award.”
The White House cited Rowley “for revolutionizing cancer research, diagnosis and treatment through her discovery of chromosomal translocations in cancer, and in her pioneering work on the relationship of prior treatment to recurring chromosome abnormalities, for epitomizing the 'bench to bedside' philosophy in her application of basic discoveries to clinical medicine, and for her leadership nationally and internationally in the oncology and biomedical communities.”
That kind of talk only embarrasses Rowley. Perennially humble, she doggedly insists that her discoveries depended heavily on the help of many others -- scientific colleagues in her laboratory, the oncologists taking care of the patients, the pathologists who helped to establish a precise diagnosis, and most of all the unfortunate few, like Claire, who happened to cross her path and were willing to share a little bit of their mixed-up blood.
