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PROFILE: Mary Lois Murphy

Medical researcher pioneered use of chemotherapy for children and advanced the field of pediatrics

Copyright © 2008 by E. A. Kral

Among the early pioneers in cancer research and the field of pediatrics in the mid-20th century was Dr. Mary Lois Murphy, a native of Sioux County, Nebraska. For almost five decades, she worked not only to discover the use of chemical treatments for children's cancer but also to raise the status of her profession.

After earning her bachelor's degree from the University of Nebraska-Lincoln in 1939, the petite, 5-foot-tall Murphy embarked on graduate studies in chemistry, at the time the only woman to do so. While taking a course in physiological chemistry, she decided to pursue a career in medicine. And from 1941 to 1944, she was one of only two women in a class of 100 medical students to study in a war-time accelerated program at the University of Nebraska Medical Center (UNMC) in Omaha.

Upon graduation, Dr. Murphy could not practice her internship in the state of Nebraska because its hospitals at the time did not have living quarters for women interns. So Dr. C.W. Poynter, Dean of the UNMC, helped her obtain an internship at Women's Medical College at Pennsylvania which had been founded in 1850 by a group of male Quaker reformers to educate women as doctors and was at first called Women's Medical Hospital. The institution closed in 2003.

At this college, she decided to pursue a career in pediatrics (the medical science concerned with the hygiene and diseases of children), and applied for residency at children's hospitals in Boston and Philadelphia. But the open positions were reserved for men returning from World War II.

After reading American Medical Association want-ads, she noticed a pathology residency was available at Children's Hospital in Washington, DC, applied for the position, and was resident there for a year.

On one occasion, the distinguished Harvard Medical School pediatric pathologist Dr. Sidney Farber gave a lecture, and upon her speaking with him afterwards, he said, "Dr. Murphy, there's no pediatrician who has your interest in cancer. Keep it up!" This inspired her to begin work in the field of pathology (the science of studying the causes of disease) at Washington, DC.

Farber was to become nationally known for founding in 1947 what eventually became the Dana-Farber Cancer Institute, and for his pioneering work in using drugs for treating malignancies in children, he was presented with the prestigious Albert Lasker Award in 1966.

This was still the era before society seriously addressed inequality and sex discrimination issues, according to Margaret W. Rossiter, author of Women Scientists in America: Struggles and Strategies to 1940 (Johns Hopkins University Press, 1982).

In a recent interview, Dr. Murphy recalled she did not realize at the time that these particular discriminatory obstacles had existed, partly because of her early background in Nebraska and partly because of intensely pursuing her interests in finding solutions. And she worked in an environment where possibilities for professional advancement developed with outstanding, innovative male researchers.

From 1947 to 1951, she continued her residency at the Children's Hospital in Philadelphia, under Dr. T. F. McNair Scott. On occasion, she also assisted C. Everett Koop, who later became Surgeon General of the United States from 1982 to 1989, and gained fame for promoting awareness of such issues as tobacco danger, AIDS, organ transplantation, and the rights of the disabled.

During the late 1940s, interest in malignant tumors rested in the field of surgical pathology, and the use of chemotherapy was virtually unknown. Moreover, pediatricians--who had no cancer treatments available--were inclined to refer patients to surgeons or radiation therapists.

Aside from Murphy's affiliation with Children's Hospital in Philadelphia for one year, she was chief resident at the nearby Camden, New Jersey, Municipal Hospital for Contagious Diseases, where she cared for many patients with polio and other infectious diseases, and participated in clinical trials of several new antibiotics and adrenal hormones.

After she had to treat members of a high school football team that had contracted polio, she found the work too burdensome for her physical stature. At that point, Dr. Scott recommended her to Dr. Joe Burchenal at Memorial Sloan-Kettering Cancer Center in New York City.

This became a turning point in her career. It was during World War II that Dr. David A. Karnofsky worked in chemical warfare, conducting secret experiments. On one occasion, an accident occurred where a tank of mustard gas dropped on the floor, and spilled on the workers. The doctors noticed the nitrogen-based chemical decreased the lymph nodes on the affected workers.

In 1947, Karnofsky was allowed to publish a research article about this discovery, but no one paid much attention until Murphy read it in the early 1950s.

By 1952, she began pioneering work at Memorial Sloan-Kettering Cancer Center (MSKCC) in clinical trials of cancer chemotherapy in children, a newly developing field at the time when leukemia was a 99 percent fatal disease. (The disease causes derangement of the blood-making organs, resulting in excess formation of white blood corpuscles.)

Under the direction of Burchenal, Karnofsky, and others, she soon took a leading role in tests of several new drugs for childhood leukemias. One of her responsibilities was to gain permission from parents to give their children drugs not previously administered to humans.

In 1953, she treated the three-year-old daughter of George H. W. Bush (later the 41st U. S. President) for leukemia. "Despite the best treatment, she lived only five or six months. Nobody lived any longer than that until the mid-1960s," Murphy stated in an interview for a profile published in the UNMC Alumni News, Fall 2006.

Aside from procedures established for patient/parent informed consent, Murphy discussed with MSKCC researchers appropriate and necessary changes in doses. Many test drugs were used in mice growing transplanted cancer cells to learn if drugs would suppress cancer cell growth. After toxicity studies in many animals, "if the drug was working, we would select one of the drugs to be tried in humans."

In 1956, she and Burchenal initiated the organization of a nationwide cooperative effort against childhood cancer. At first, this multi-institutional group was called Acute Leukemia Group A, and after Murphy succeeded Burchenal as its chairperson from 1958 to 1965, it expanded its scope to include the spread of solid tumors in children. Ultimately, it became known as the Children's Cancer Study Group, considered decades later as a highly productive advancement in medicine and pediatric care.

Aside from her interest in soft-tissue cancers, she also became a pioneer in teratology, the study of birth abnormalities. Researchers under the direction of Karnofsky had injected experimental chemicals into chicken eggs. After administering various drugs and doses, Karnofsky found some chicken eggs had embryos with abnormal feet and wings.

So Murphy established a rat laboratory with Karnofsky to test varying doses of chemicals on pregnant rat fetuses. After showing that single doses of chemical agents in the rats could pass through the placenta, causing birth defects, she developed cancer-inhibiting chemicals on the embryonic tissue in the pregnant rats.

As a result, the genetics laboratory at Bar Harbor, Maine invited her to be a summer investigator because she had the chemicals to conduct the experiments. She became known worldwide as an expert in teratology, and organized and hosted with her MSKCC colleagues the first meeting of the Teratology Society in New York City in 1961.

From 1965 to 1976, she served as chairperson of the Department of Pediatrics at MSKCC, where she initiated a revolution in the field of pediatric oncology (the study of tumors). Not only did she recruit a staff of pediatricians and specialists in surgery, diagnostic radiology, neurology, cardiology, anesthesiology, and nursing, but she also raised the status of pediatricians.

Murphy also created and implemented in 1968 the first pediatric day hospital at MSKCC, and helped develop treatment guidelines that increasingly allowed children with cancer to play, to learn, and to lead normal lives. Visits to the day hospital doubled in five years, and the cure rate of most solid tumors reached 70 to 80 percent.

The multidisciplinary rules established under her direction to treat all solid tumors in children as well as leukemia became a model for other departments of pediatric oncology nationally and internationally, and correlated with treatment of cancers in adults.

After 1976, she served as professor of pediatrics in Therapeutic Research at MSKCC and at Cornell University Medical College. Upon her retirement in 1992 from Memorial Sloan-Kettering Cancer Center, Dr. Murphy was honored with a one-day symposium in which speakers credited her with providing the groundwork for the present-day high cure rates for children with cancer. She was with MSKCC for 41 years.

During her career, she was invited to lecture in many countries of the world, and was author or co-author of 125 published research articles, 25 book chapters, and 105 abstracts.

Also significant was her work with research colleagues in the 1950s and 1960s who became recognized nationally for their achievements.

Dr. David A. Karnofsky, who died in September 1969 at the age of 55, was called by Time as "one of the world's outstanding researchers in the discovery and development of drugs for the treatment of cancer," and was posthumously honored by the American Society of Clinical Oncology in 1970 by establishment of its annual Karnofsky Memorial Award and Lecture.

And Dr. Joseph A. Burchenal, who died in March 2006 at the age of 93, was considered a pioneer in the field of chemotherapy, and became co-recipient of the Albert Lasker Award in 1972.

Murphy's notable recognition was inclusion of her profile/photo in an article titled "American Women: The Doers," published in the May 1967 Vogue Magazine. She was among 100 women of distinction so honored, with her photograph taken by the distinguished New York City photographer Horst P. Horst.

In 1973, she was recipient of an honorary doctor of science degree from the University of Nebraska Medical Center.

Murphy was also one of the doctors featured in the article "Good News! Meet The First Generation of Kids Who Beat Cancer," published in the March 1990 issue of Good Housekeeping.

One of her former patients was Michelle Merklinghaus Natali, who as a high school junior in 1981 received treatments from Dr. Murphy for two years at MSK, followed by complete recovery. As a child before becoming ill, Michelle performed under the stage name Shelley Bruce in the starring role of the Broadway musical Annie from 1977 to 1979.

In January 1981, George and Barbara Bush made special arrangements for Dr. Murphy to attend the inauguration of Ronald Reagan, the 40th U.S. President. After seeing Reagan riding a horse down the street on the way to the Nation's Capitol for the ceremony, Murphy realized she could for the first time discuss her early years on a western Nebraska cattle ranch with her medical colleagues without diminishing her accomplishments in the medical sciences.

Born in 1916 on a ranch three miles west of Curly, Sheep Creek Township in Sioux County, the northwest corner of Nebraska, one of five children (three daughters and two sons) of John C. and Mattie Bocock Murphy, the petite Mary Lois rode horseback to the nearby rural school through the 3rd grade.

Of those early years, she also recalled that "neither of my parents had gone to any school of significance. They had established my father's ranch and his two brothers' adjoining ranches. They dug their own well--100 or 200 feet--and it had a pump and a windmill. We got water for ourselves out of an elevated metal container (the tanks were for cattle). They also built their own sod house, and they never saw a doctor, to my knowledge."

After her family moved to Alliance, she attended St. Agnes Academy boarding school as a day pupil, then in the ninth grade, the Murphys moved to Lincoln. While attending Lincoln High School, the city's largest public high school with an enrollment of 1,500, she took numerous courses, including history, mathematics, chemistry, and physics. She recalled, "While I was in high school, I filled myself with as much as I could. It was the greatest experience. There were athletics and after-school clubs like photography and art. I was really lucky."

She was the financial manager for the student newspaper, and her homeroom teacher was Elsie Cather, who not only helped her with developing friendships but was also the sister of renowned author Willa Cather, who had earned the 1923 Pulitzer Prize for fiction, and later was inducted into the National Women's Hall of Fame at Seneca Falls, New York.

After graduating from Lincoln High in 1935, she tried to get a job to help her parents, for her father was a carver of tombstones and her mother sewed items for neighbors and others. After applying for several jobs "by walking around and going in to apply, I didn't get any. Finally, I just decided that because I was too little to get a job, I might as well go to college." And, of course, she earned her bachelor's degree from UNL in 1939.

When Murphy wanted to pursue graduate courses in chemistry at UNL, she was accepted but could not receive any of the money that came from oil companies, she recalled, so "the head of chemistry at Lincoln High, Mariel C. Gere, gave me a job once or twice a week to supervise the students who were taking chemistry there. That's how I paid my college chemistry laboratory fees."

Gere, who retired in 1941 after teaching more than 40 years, was a daughter of pioneer Lincoln business and cultural leader Charles H. Gere, who was posthumously honored in 1969 by the Lincoln City Libraries with a branch library named after him.

Profiles of Mary Lois Murphy's career may be found in the American Journal of Pediatric Hematology / Oncology, Vol 8 (Spring 1986) 58-62 and in the UNMC Alumni News, Vol 139 (Fall 2006) 12, 14. There is also an entry in American Men and Women of Science, Vol 5 (2005) 571, and an obituary was published in the April 27, 2008 New York Times.

Dr. Murphy died at age 91 on April 8, 2008 in New York City, her home since 1952. Though retired from active practice since 1992, she continued to attend weekly meetings at MSK, and at the age of 89 applauded the improved training pediatricians now receive that helps them make an early diagnosis of cancer so that children can be referred sooner to an established treatment center. She also remained in communication with the UNMC and relatives in Nebraska.

For more information, consult "900 Famous Nebraskans" on the Internet at www.nsea.org or www.byjake.com/gagecountymuseum or www.nebpress.com.