Tuesday, October 29, 2013

How chemotherapy was discovered

Dr. Gustaf Lindskog was a leading thoracic surgeon and chair of the Yale Department of Surgery in 1942. It was a perilous time: The United States feared that Germany was about to unleash chemical weapons against Allied soldiers.

Yale School of Medicine researchers had been participating in a top-secret government program to develop antidotes to these agents. While focused on the lethal effects of nitrogen mustard, one of the most deadly chemical weapons of the time, they noticed that it appeared to also kill cancer cells in mice.

Drs. Louis Goodman and Alfred Gilman of pharmacology had treated a mouse with an advanced lymphosarcoma. After just two injections of nitrogen mustard, the tumor began to soften and shrink. It was an exciting discovery, but after another round of treatment, the tumor grew resistant, and after 84 days the mouse died.

Still, the physicians considered the extended lifespan remarkable, and they started wondering whether nitrogen mustard could be used to help humans with cancer. They turned to their colleague at Yale, Dr. Gustaf Lindskog.

Lindskog had a patient, known only as J.D., who was 47 years old and dying. By the time he was admitted to New Haven Hospital (later to become Yale-New Haven Hospital) on Aug. 25, 1942, J.D. had massive head and neck tumors that had cut off his ability to speak, eat, or move his head. Months of radiation had done little to no good.

Lindskog approached his patient about receiving this experimental treatment with nitrogen mustard. Knowing he had run out of other options, J.D. willingly agreed and two days later became the first human patient to receive intravenous chemotherapy for cancer. In administering the treatment, Gustaf Lindskog launched a protocol for cancer care that would save millions of lives over the next 70 years. ...

After his first chemotherapy treatment, J.D. received injections for several days, but because of the secrecy and censorship required, doctors couldn't even note on his record that he was receiving nitrogen mustard — they referred to the injected material as "a lymphocidal chemical," or "substance X."

By Aug. 31, six days after his first injection, 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 Sept. 6 his condition had improved markedly, and a month into his treatment, his cancer was undetectable.

Unfortunately, the cancer cells that lingered had become resistant to the nitrogen mustard. J.D.'s lymphosarcoma returned, and this time there was no treatment. He went downhill quickly, and on Dec. 1, 1942, the 96th day of his hospital stay, J.D. died. ...

Times were different then. Research could be conducted fairly easily. “It’s unimaginable, compared to today’s world,” [grandson and Yale orthopedic oncologist] Dieter Lindskog says. “He had a drug and a patient. He talked to him, told him it was experimental, and gave it to him. Today, that would be a nine-month process.”
--Helen Dodson, YaleNews, on a silver lining to World War II