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It probably goes without saying that throughout the years, cancer sufferers have been subjected to a great variety of experimental treatments that ranged from the simplest to the most bizarre. Every corner of the world has been searched, every twig, nut and berry examined, and every method tried in the quest to find a cure or at least some kind of alleviation.

 

The first half of the twentieth century was dominated by surgery and radiology when it came to cancer: small tumors were removed and X-ray irradiation was used to kill the cells that escaped the surgery. This was the “Slash and Burn” era of medical history, until a third member, namely “Poison”, came along in a curious way.

 

“The substance smelled and had the colour of mustard but was not a gas at all. It was actually an oily liquid that had the ability to finely disperse in the air and cause major damage to anyone that it could reach.”

 

The world was introduced to mustard gas and its effects in the First World War by the German Army. The substance smelled and had the colour of mustard but was not a gas at all. It was actually an oily liquid that had the ability to finely disperse in the air and cause major damage to anyone that it could reach. Mustard gas affected the respiratory system by practically burning the lining of its organs; it also harmed the eyes and when it got in contact with the skin, it produced horrible blisters. Around 91,000 soldiers died from exposure to the gas and many more remained with respiratory problems for life.

 

Although the Geneva Protocol on Gas Warfare banned the use of poisonous gases in 1925, during World War II, both sides kept secret stashes just in case one of them decided to ignore the decision. The United States government took an extra precaution and tried finding an antidote for the moving poison.

 

“Although the Geneva Protocol on Gas Warfare banned the use of poisonous gases in 1925, during World War II, both sides kept secret stashes just in case one of them decided to ignore the decision.”

 

In 1942, two pharmacologists, Louis Goodman and Alfred Gilman, from the Yale School of Medicine were assigned to study mustard gas and find an antidote. The task itself was very challenging as the so called gas had an oily nature, was sulfur-containing and wasn’t water-soluble. These aspects made it quite impossible to work with in the laboratory. Changes had to be made, so, the two brilliant researchers replaced the sulfur atom of the compound with a nitrogen one and obtained nitrogen mustard. The new substance had the same deadly properties as the original but was now easier to manage.

 

In order to produce an antidote, they began experimenting on animals, more exactly, they administered nitrogen mustard to rabbits. A fast decrease in the number of white blood cells was noticed, especially in the case of lymphocytes that seemed to be the most sensitive to the substance. This raised an extraordinary question in the pharmacologists’ minds: could nitrogen mustard work in the case of lymphoid cancers?

 

Their curiosity led them to Dr. Thomas Dougherty, from the Department of Anatomy. Although his focus was on leukemia, he agreed to test the compound on lymphoid tumors in mice. The experiment was carried out on one of his specimens that had an advanced tumor and was about to die. In the first phase, the mouse had been administered two injections of nitrogen mustard, followed by a few daily doses. The tumor regressed miraculously and couldn’t even be felt through the skin anymore. The treatment was stopped and the tumor kept regressing for a month. After this period it began growing again. A second phase of treatment commenced but showed a lessened effect upon the problem. At the third series, the tumor had become unresponsive and resistant to the substance. However, this was not registered as a negative result because in the end, the mouse lived 84 days more than it was possibly expected. The experiment was repeated on a group of mice that had lymphoid tumors and the results were confirmed, but the substance had no effect on mice with leukemia. About this chance order of things, Dougherty wrote: I have often thought that if we had by accident chosen one of the leukemic mice, in which there was absolutely no effect, we might have dropped the whole project.*

 

A new way of dealing with cancer had been discovered and it just had to be tried on a human subject. The candidate was a 48 year old man with advanced lymphoma (tumoral masses spreaded around the heart, neck and armpits). Doses were given following… intuition, as there was no precedent to go about and the result turned out to be the one they had hoped for. The patient’s tumors had the same response as in the case of the mice.

 

This method had its side-effects and was far from being a cure, but nevertheless, it was the starting point of chemotherapy and represented a way of giving cancer patients more days to live.  

 

 

R.F.I.

*Winters, Robert. Accidental Medical Discoveries: Tales of Tenacity, Sagacity, and Plain Dumb Luck, Denmark, 2013, pp. 165

1 comments on Nitrogen mustard: from ending lives to prolonging them
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    Giulietta Nero July 13th, 2016 at 7:53 pm
    This was so interesting to read. Medical history in the making. At least we know how chemo began.
    Reply