The Register Citizen (Torrington, CT)
Yale research led to discovery of chemo
The year was 1942. The country was in the middle of World War II, and two Yale pharmacologists were hired by the Department of Defense to study the effects of nitrogen gas as a therapeutic agent.
The project was top secret, and pharmacologists Alfred Gilman, a faculty member at the Department of Pharmacology, and Dr. Louis S. Goodman, a faculty member at the Yale School of Medicine, were studying whether mustard agents could be used to stop the growth of rapidly dividing cells such as cancer cells.
While Gilman and Goodman were able to utilize nitrogen gas in a positive way, when it was unleashed on the battlefield in World War I, it was one of the deadliest chemical weapons available.
“Nitrogen mustard had a couple of uses,” said Dr. Roy Herbst, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital. “Not only for positive use, as we use it in cancer — it’s not used so much anymore — but it was used in wartime, as chemical warfare.”
It was this latter usage that necessitated the original scientists, Gilman and Goodman, to conduct their studies secretively. The results were not published until 1946.
“Goodman and Gilman, long before their time, in the ’40s, they
understood nitrogen mustard and they synthesized it,” said Herbst. “They were chemists and they synthesized these compounds that would kill dividing cells.”
“The Birth of Chemotherapy at Yale-New Haven Hospital” is the headline on a prominent exhibit at the hospital located in the “Octagon” in the West Pavilion. A copy of the original medical notes, along with an explanation of Gilman’s and Goodman’s work and photos of the pharmacologists and the hospital, are on display.
“This is what’s technically referred to, in the West Pavilion or Yale New Haven Children’s Hospital, as The Octagon,” said Mark D’Antonio, hospital media relations coordinator, standing at the location of this prized, wall-mounted exhibit.
“This was probably put here as one of the more prominent, ‘We’re proud of this accomplishment,’ moments in cancer care here at Smilow Cancer Hospital and Yale Cancer Center, so it’s probably one of those ... things that you look back on and say with pride, ‘This was the birth of chemotherapy,’ ” he said.
The entry in the “Progress Notes notebook No. C12629” pinpoints the exact time the initial injection was done on the patient. “8/27 10 am Intrav injectn 0.1 mgm/kg (8mgm in 50 cc physio saline) of synthetic lymphocidal chemical. L. Goodman,” was entered by Goodman in cursive writing with a fountain pen.
The explanation in the exhibit reads, “On August 25, 1942, a patient known only as J.D. was admitted to the then New Haven Hospital, dying of lymphosarcoma. His physician, Gustaf E. Lindskog, MD, believed that J.D. might benefit from the new tumor-reducing therapy his colleagues had developed and with the patient’s permission, administered 10 daily of ‘substance X,’ the wartime code name for nitrogen mustard.”
While the nitrogen mustard killed the dividing cells, it also killed healthy cells, as they discovered with J.D. While his cancer appeared to be getting better with the treatment, the nitrogen mustard also affected the good cells. He died two months after getting the first injection.
“They treated him with these drugs and his tumor shrank,” explained Herbst. “Now, he didn’t survive long because his tumor shrank but his normal cells were affected, too, so he developed infection and low blood counts and anemia, but it was the first demonstration that you could use something to kill some cells and attack cancer.
“So it really is a (beginning of a) modern-day era of treating cancer in ways other than just surgery,” he added.
“Marie Curie had done (studies), so we already had radiation, but cancer is a disease of cells that spread throughout the body, so it was the first demonstration of using drugs to systemically kill tumor cells in the body,” Herbst said.
Curie, with her husband, was “awarded half of the Nobel Prize for Physics in 1903, for their study into the spontaneous radiation discovered by Becquerel, who was awarded the other half of the Prize,” according to the site nobelprize.org. “In 1911 she received a second Nobel Prize, this time in Chemistry, in recognition of her work in radioactivity.
She also received, jointly with her husband, the Davy Medal of the Royal Society in 1903 and, in 1921, President Harding of the United States, on behalf of the women of America, presented her with one gram of radium in recognition of her service to science.”
Herbst said he is thankful for the work of Gilman and Goodman. He knows his career is directly related to the work these pharmacologists did more than 77 years ago. “It really is a historic event and it all happened at Yale,” he said.
Kathryn Southworth Gilman, of Texas, said her father-in-law was not one to boast about this accomplishment.
“He was a very modest and quiet man,” she said. “I don’t think I knew about it. I certainly never knew it through him. Through my husband, I guess, is probably the only reason that I knew about it.
“He was very soft spoken and a lovely man, but not one to discuss things like that, at least not with me,” she said. “He had quite a career in addition to that and that’s the only thing I remember very much about.”
Gilman’s career included work at Columbia’s College of Physicians and Surgeons and the Albert Einstein College of Medicine.
“He had a Yale connection at the end of his career, too,” she added. “He came back to live in New Haven and he had an office at the medical school and would go over there at least for a few years. He just kept his finger in it even though he was retired.”
Goodman went on to teach at the University of Vermont and the University of Utah.
They also left a lasting legacy with their authorship of “The Pharmacological Basis of Therapeutics” in 1941.
Yet, it was their work on the future of chemotherapy at Yale that shaped the future of Herbst’s career.
“It opened up the whole field. There would be no field,” Herbst said. “There would have been no oncology department. There would have been no American Society of Clinical Oncology. There would have been no development of chemotherapy.
“It might have come with another drug, but this opened up the whole field,” he added. “This got people working together. It really was the beginning of the field.”