From chromosomes to cancer cures: the lifesaving work of Dr. Janet Rowley

The magic of meeting Janet Rowley

A few years back on an early spring day I was heading to the University of Chicago Cancer Research Center with the idea of launching a non-profit committed to curing lymphoma, leukemia, and myeloma fresh on my mind. As I approached the building, I noticed a distinguished, graceful lady peddling up in a red bicycle. I waited a couple of moments by the elevator in the hope of having the opportunity to meet her. As we rode up the elevator, I introduced myself and told her about our modest new venture. She seemed pleased with our mission and introduced herself. I told her that, for a blood cancer survivor like me, meeting her was like meeting Frank Sinatra or a rock star.

Of course, that distinguished lady was none other than Dr. Janet Rowley – the matriarch of cancer genetics, the researcher who has received all of the prestigious scientific awards – who had recently received the Presidential Medal of Freedom. It did not take long for me to learn that this authentic, modest lady was focused on the science, not on the accolades. As I started singing her praises Dr. Rowley disarmed me with her good natured laugh and said “just call me Janet.”

For a moment, I forgot that I was at the University of Chicago Cancer Research Center to interview its director, Dr. Michelle Le Beau. Dr. Le Beau, a renowned, award-winning researcher in her own right, is a protégé of Dr. Rowley. In the interview, Dr. Le Beau touched on how she was influenced by Dr. Rowley and how Dr. Rowley’s work changed the face of cancer research.

Before leaving, I stopped over to talk with Dr. Rowley. She introduced me to her young colleague with whom she was discussing their current lymphoma research project. Dr. Rowley was asking her young colleague questions and was genuinely interested in his responses. Too many of the august scientists that I have met over the years were more inclined to lecture young scientists than to listen to them. But it made sense that the greatest cancer researcher of our time would be curious, passionate, focused on the current project, and eager to be working with young colleagues. Dr. Rowley was both teaching and learning at the same time.

At that moment, I realized that Dr. Rowley’s true legacy extends well beyond her own groundbreaking work to the work already done and the work to be done by so many of the other researchers that she has trained and inspired. She says that science is tough and researchers must have perseverance to sustain them when their well-planned studies do not turn out as expected or hoped and they must be committed to looking for the answers. My wife, Charlene, and I had the pleasure of dining with Dr. Rowley and her husband, another important reasearcher, a couple of years ago and raised the idea of interviewing her.

Riding her bike to work every day, making her own photocopies, finding joy in working with young researchers, and growing giant green beans in her Hyde Park garden are all part of the magic of Dr. Rowley.

Before the legendary work

Dr. Rowley may not have been born with a silver microscope in her hand, but she was blessed with a potent combination of brilliance, ingenuity, curiosity, pragmatism, keen observational powers, patience, and perseverance. She earned her bachelor of philosophy degree, her bachelor of science degree, and her doctor of medicine degree (at age 23) all from the University of Chicago. She worked part-time until the youngest of her four sons was 12 years old. Dr. Rowley worked as a physician at the Infant and Prenatal Clinics in the Department of Public Health, Montgomery County, Maryland. In 1955, she took a research post at a clinic and helped children with developmental disabilities. It is somewhat ironic that Dr. Rowley later would do more to the save lives of children and adults as a result of her work in the laboratory, than any physician could do treating patients in a clinic.

In 1962, after a year in England as an NIH trainee studying the pattern DNA replication in normal and abnormal human chromosomes, Dr. Rowley returned to the University of Chicago. Dr. Leon Jacobson asked Dr. Rowley to apply the methods of quinacrine fluorescence and Giemsa staining that she refined for the study of chromosomes to patients with leukemia. As Dr. Rowley explains, all of her conditions were met, she could continue the research that she was working on and she would get paid for doing it!

University of Chicago and Hyde Park have remained Dr. Rowley’s home. Since 1984, Dr. Rowley has been the Blum-Riese Distinguished Service Professor at the University of Chicago.

From chromosomes to cancer cures

Dr. Rowley’s landmark discoveries date back to the 1970s. Her first big discovery came in 1972. She found that the chromosomes of a patient with acute myeloid leukemia (AML) appeared to have “translocated.” A portion of chromosome 21 broke off and moved to chromosome 8 and a portion of chromosome 8 had moved to chromosome 21. She later observed this translocation in other patients with AML.

Dr. Rowley next discovered that patients with chronic myeloid leukemia (CML) had a different translocation. One end of chromosome 22 was exchanged for a piece of chromosome 9. Because of this transfer, important genes that regulated cell growth and division were no longer located in their normal position. The altered 22 chromosome, known as the Philadelphia chromosome, gives the CML patient’s body new instructions that result in both the over production of white blood cells and development of other immature blood cells that are incapable of full development. Left unchecked, these actions will result in the person’s death. This “translocation” of chromosome 9 and chromosome 22 is found only in the CML cells and in a portion of patients with acute lymphoblastic leukemia. In 1977, Rowley identified the translocation of chromosomes 15 and 17 as being responsible for a rare form of leukemia called acute promyelocytic leukemia.

Importantly, Dr. Rowley’s work established that cancer is a genetic disease. She proved that mutations in critical genes lead to specific forms of leukemia and lymphoma and she demonstrated that one can determine the form of cancer present in a patient directly from the cancer’s genes. Dr. Rowley turned the traditional thinking that chromosomal abnormalities were the result of the disease on its head. To be sure, there were some doubting scientists at first, but her work has proven to be very influential and has resulted in scores of translocations being identified for a wide-range of cancers.

Dr. Rowley’s work changed the way cancer was understood, opened the door to development of drugs directed at the cancer-specific genetic abnormalities, and created a paradigm that continues to drive cancer research today. In short, Dr. Rowley ushered in the age of targeted cancer treatment.

Dr. Rowley’s work led to life-saving treatments for patients with CML. The National CML Society tells us that, prior to 2001, traditional therapies such as chemotherapy were used, and the average life expectancy after diagnosis was three to five years. Now, according to the National CML Society, most patients today can expect to live a normal lifespan as long as they have access to treatment and adhere to the prescribed treatment. The reason for this huge reversal in survival fortune for CML patients is a new form of targeted drug therapy that has been available to patients since 2001. This category of drugs, known as tyrosine kinase inhibitors, interferes with the signal activity that results in the proliferation of cancer cells. More specifically, these drugs target the BCR-ABL protein associated with the Philadelphia chromosome and, like many of today’s targeted therapies, leave healthy cells alone. These treatments have transformed this previously fatal leukemia into a manageable chronic disease for most patients.

The oldest of these treatments is imatinib mesylate (Gleevec), which has been the standard initial therapy for chronic phase CML since 2001. Most but not all patients succeed with this drug. Some CML patients experience side effects of Gleevec that are significant enough to require them to discontinue the drug. In some patients the disease becomes resistant to Gleevec. In 2010, two additional oral drug therapies – dasatinib (Sprycel) and nilotinib (Tasigna) – were approved for newly diagnosed chronic phase CML patients. Neither Sprycel nor Tasigna has been shown to result in longer survival at this point. Some findings suggest that these drugs may produce faster complete cytogenetic and molecular response that might prove to be associated with better long-term outcomes. Additionally, these drugs provide options for some patients who cannot take Gleevec. Two additional tyrosine kinase inhibitors, bosutinib and ponatinib, are now being used in clinical trials and are expected to become available for CML patients in the future.

Dr. Rowley’s work has been transformative. It has led to the development of lifesaving treatments. It also has led to the identification of other translocations responsible for other forms of cancer. Last month, the United States Food and Drug Administration approved Gleevec for children with AML.

America should not sequester Dr. Rowley’s work or cancer research

The reality is that government funding of cancer research is decreasing at a time when it should be increasing. Last year, we reported that the National Institutes of Health (NIH) lost approximately 13% of its purchasing power over the last 8 years. For years, America’s investment in cancer research has been declining in real dollars. What’s worse, federal funding of research now also is declining in nominal dollars. The $320 million in cuts to NIH for 2011 translate into $45 million in cuts to the National Cancer Institute (NCI). As a result, existing grants have been cut by 3%, the number of grants awarded will fall by 10%, and cancer centers will be cut by as much as 5%. Only 7% of NIH grants have guaranteed funding. The real and now net decreases in cancer research have a significant, long-term negative impact because less bright and talented people enter the field and cutting edge research designs – the type that lead to major breakthroughs – are proposed and approved less often because researchers are more conservative in their proposals. http://www.examiner.com/article/let-s-be-americans-not-american-ts-when-it-comes-to-cancer-research

The American Association for Cancer Research recently recommended that Congress provide the NCI with annual budget increases of at least 5% above the biomedical inflation rate. It believes that this level of sustained support will enable the future scientific advances needed to seize today’s scientific momentum, capitalize on prior investments in cancer research, save countless lives, and spur innovation.

Dr. Rowley points out that the impending sequester will take a further toll on cancer research. Investment in cancer research is one of the best investments made by America. JAMA reports “investments in cancer R&D have been quite worthwhile – producing a value to society far in excess of costs – we estimated a consumer surplus of $1.9 trillion. Thus, even when increases in cancer costs are taken into account, cancer survival gains were of tremendous value to patients.” jama.ama-assn.org/content/303/11/1084.short. Few areas of government spending can match the fabulous return on investment realized from cancer research. http://www.examiner.com/cancer-in-chicago/it-is-time-to-win-the-war-against-cancer-not-to-cut-cancer-research-funding.

It is beyond cavil that there are many areas in which spending cuts are necessary and appropriate, but one area that should be exempt from cuts is cancer research. Cancer research saves lives.

It is incumbent upon us to support and fund cancer research

Currently, our government’s commitment to curing cancer – as contrasted with the tremendous commitment demonstrated by so many dedicated patients, family members, advocates, physicians, and researchers – is underwhelming.

Dr. Rowley hopes that private philanthropy will help fill the void of decreasing federal dollars for research. Indeed, private fundraising always has played a critical role in cancer research and the private sector is responsible for more cancer research dollars than the government. But now more than ever is the time for all of us to get together and support the lifesaving research of Dr. Rowley and other great researchers.

At age 87, Dr. Rowley continues her work from her laboratories at University of Chicago in earnest. As a result of the human genome project and the brilliant work of Dr. Rowley and many other scientists, future research will have even a greater impact and will save more lives. Dr. Rowley is not only a Chicago treasure, but a national and international treasure as well.

Hopefully watching the accompanying video of Dr. Rowley will inspire you to become involved in donating or raising money for cancer research. Our thanks to University of Chicago’s Nina Restruccia for helping to arrange our interview of Dr. Rowley.

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, Cancer Examiner

Scott Seaman is a partner and commercial trial lawyer at Meckler Bulger Tilson Marick & Pearson LLP. He is a member of the Board of Selectors of the Jefferson Awards for Public Service (Nobel Prize for public service). Scott is a prolific author/speaker on legal, business, insurance, and...

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