Happy birthday: 75 years of chemotherapy is worth celebrating

A wartime mustard gas explosion led to the development of a life-saving treatment

One in three of us will develop cancer during our lives. When it happens we expect to be treated with a combination of surgery, radiotherapy and chemotherapy. Chemo is the “youngest” of these cancer treatments and is one of the reasons why the overall survival rates for cancer have doubled in the past 40 years.

This week, August 27th to be precise, marks the 75th anniversary of the first use of chemotherapy in a cancer patient. It’s an interesting story, juxtaposing military horror with medical advancement, and with an Irish angle of sorts.

Mustard gas, first produced during the first World War, was a deadly chemical that killed some 10,000 Allied troops at Ypres, Belgium, in 1917. But it took an accident during the second World War in the port of Bari, Italy, for the potential medical value of mustard gas to emerge from the mire of war.

During a German air raid in December 1943, some 1,000 people were exposed to the SS John Harvey's secret cargo composed of mustard gas bombs. Dr Stewart Francis Alexander, an expert in chemical warfare, investigated the tragic aftermath. Autopsies of the victims suggested that suppression of lymph and myeloid tissue had occurred after exposure to the gas, leading Alexander to speculate the agent could be used to stymie the growth of certain types of cancerous cells.

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Meanwhile, a year prior to the Bari accident, two pharmacologists from the Yale School of Medicine, Louis Goodman and Alfred Gilman, were recruited by the US department of defence to  investigate ways of protecting against mustard gas exposure.Their first step was to exchange a nitrogen molecule for a sulphur one in order to make mustard gas more stable.

Prof Susan Smith of the University of Alberta, in her recent book Toxic Exposures, explains how the pharmacologists were studying the effects of nitrogen mustard on rabbits when they spotted how it affected both lymph glands and bone marrow. Subsequent experiments on lymphoma – a cancer of the lymphatic system – in mic - showed how nitrogen mustard dramatically shrank the tumours.

They then approached thoracic surgeon Gustafson Lindskog to conduct a therapeutic experiment on a patient, JD. A Polish immigrant who worked in a local ball-bearing factory, he had developed enlarged tonsils and jaw pain some two years earlier. A biopsy of multiple enlarged lymph glands confirmed JD had a form of cancer called lymphosarcoma. Initially responsive to radiotherapy, in August 1942, he was admitted to hospital with headache, breathing problems and difficulty swallowing. His prognosis was grim.

JD’s mass of tumours were pressing on his trachea and gullet, causing him considerable discomfort. His treatment began on August 27th, 1942, when Dr Goodman gave him his first injection of nitrogen mustard. By August 30th he told nurses his throat felt better and less constricted. He received the last of the series of nitrogen mustard injections on September 6th; according to his medical notes, the tumour had reduced in size, his severe headaches had disappeared and he could finally eat and sleep more comfortably.

However the cancer remission was short lived and he required more chemotherapy in late October. But the tumour had become resistant to the nitrogen mustard and JD passed away on December 1st.

That the chemotherapy was a short-lived success is not the point. The demonstrable reduction in tumour size following treatment with nitrogen mustard was a landmark in the history of medicine.

What about the Irish connection? Records show that in the north Irish Sea, a deep-water trench called the Beaufort Dyke is a resting place for nitrogen gas and other chemical warfare weapons. During work on a gas pipe line in 1995, canisters of munitions were washed up on beaches in Co Donegal and Co Antrim.

For cancer patients globally, this week 75 years ago marked the birth of chemotherapy and the beginning of its vital role in the successful treatment of cancer. mhouston@irishtimes.com