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Newly found records detail birth of chemotherapy at Yale

2/21/2011 — After years of detective work, physicians at Yale School of Medicine have recovered, and are now making public, long-lost medical records of the first patient to receive intravenous chemotherapy treatment for cancer, a seminal event that took place at Yale in 1942. Their paper, which appears online in the Journal of the American College of Surgeons, tells the story of a man with a terminal illness who became part of medical history. His courage, along with the skill of his doctors at Yale, paved the way for advances in cancer treatment that were inconceivable in his lifetime but which have since saved the lives of millions of people.

In telling the story of this patient, and the sleuthing that uncovered his medical records, the paper also corrects the historical record about this first patient in the world to receive I.V. cancer chemotherapy.

The patient, known only as "J.D." (even today, because of privacy laws, he can only be identified by his initials) was born in Poland in 1894. He immigrated to the United States at age 18. He had no known family around him, never married and lived alone in a rented four-room house in Meriden, Connecticut. He worked in a ball-bearing factory until his illness began in 1940.

His first admission to New Haven Hospital (later to become Yale New Haven Hospital) came in February 1941, for what had begun as enlarged tonsils and had grown to a full-blown lymphosarcoma, a malignant tumor of his lymph nodes. Throughout 1941, doctors tried to reduce his tumors with radiation, but the treatment provided no significant benefit.

During these early years of World War II, Yale School of Medicine researchers had been participating in a top-secret program of the U.S. government to develop antidotes to chemical warfare agents, which the government feared would be used by the Germans against Allied troops. Attention turned to nitrogen mustard, and studies of its lethal effects on mouse tumors suggested that it might also be effective against certain cancer cells, despite its toxicity. Although their research was heavily censored by the War Department, the Yale physicians began exploring nitrogen mustard for this purpose.

By the time J.D. was admitted on August 25, 1942, at age 47, his tumor mass was so large and hard that he could not move his head. Yale physicians had been looking for a cancer patient willing to undergo experimental treatment with nitrogen mustard. J.D., knowing he was dying, willingly agreed. Two days later, he received the first dose of intravenous chemotherapy, and was given daily injections in the days that followed.

By August 31, J.D. was improving. He was able to sleep comfortably in bed. Eating was easier, and he could move his head in a wider arc and cross his arms on his chest for the first time in weeks. By September 6 his condition had improved markedly, but his white blood count, which indicates levels of the immune system's disease-fighting white blood cells, was falling precipitously. A month into his treatment, his cancer was undetectable.

Unfortunately, whatever cells did remain had become resistant to the nitrogen mustard. J.D.'s lymphosarcoma made a relentless return. He went downhill quickly, suffering from bone marrow depression, bleeding and respiratory distress. On December 1, 1942, the 96th day of his hospital stay, J.D. died.

In the chaos of those war years, J.D.'s medical records were misplaced. An article appeared in a 1946 issue of the Journal of the American Medical Association about his case, but it was based on personal recollections rather than the facts that would have been contained in a medical file. As a result, there were many inaccuracies relating to the course of J.D.'s treatment, the pathology of his illness and even details about his life such as his occupation.

Two years ago, Yale physicians John Fenn and Robert Udelsman became fascinated by J.D.'s case and determined to try to locate his medical records. The problem was, they had no name, date of birth, medical record number or precise dates of treatment. They had his initials, but there were many "J.D.'s" in the files from the early 1940s. For months they sifted through the records, including pathology reports, of every "J.D." they could find. They finally found one with lymphosarcoma, but the medical record number contained errors. Thanks to a persistent archivist who sequenced the numbers and corrected the numbers, they narrowed the possibilities down to one patient. J.D.'s records were found.

Discovery of this first patient's file, nearly 70 years after his death, brought into sharp focus how new cancer therapy was in the early 1940s, but how aspects of chemotherapy were the same then as they are today: its effectiveness as a cancer treatment, and its toxicity and the risk of patient resistance.

"It was all there," said John E. Fenn, M.D., clinical professor of vascular surgery at Yale School of Medicine. "In one patient, there was the revelation that cancer would respond to chemical injections, and that chemotherapy also had potentially lethal implications in the depression of bone marrow."

J.D.'s willingness to undergo a new treatment led to decades of advances in cancer prevention and care, where the promise of chemotherapy was often fulfilled and sometimes crushed but was ceaselessly pursued. "That first proof of chemotherapy's efficacy as well as its side-effects paved the way for decades of improvement in these life-saving agents," said Robert Udelsman, M.D., M.B.A., professor and chair of surgery, Yale School of Medicine.

Fenn says, "J.D. gave us hope for the future. This one patient was responsible for the birth of medical oncology."

Yale Office of Public Affairs and Communications

Yale New Haven Hospital (YNHH), part of Yale New Haven Health, is a nationally recognized, 1,541-bed, not-for-profit hospital serving as the primary teaching hospital for the Yale School of Medicine (YSM). Founded as the fourth voluntary hospital in the U.S. in 1826, today, YNHH has two New Haven-based campuses, and also includes Yale New Haven Children's Hospital, Yale New Haven Psychiatric Hospital and Smilow Cancer Hospital. YNHH has received Magnet designation from the American Nurses Credentialing Center, the nation’s highest honor of nursing excellence. YNHH has a combined medical staff of about 4,500 university and community physicians practicing in more than 100 specialties.