Mustard gas was first used as a weapon of terror bringing chemical weapons to the battlefield. However, the properties that made it an agonising killer also made it into the basis for a frontline cancer treatment.
Mustard Gas Arrives on the Battlefield
In July 1917, troops operating in the Ypres salient, Belgium, reported a shimmering cloud around their feet and a strange peppery smell in the air. Within 24 hours, they started to itch uncontrollably and developed horrific blisters and sores. Some even started coughing up blood.
They had been poisoned by mustard gas—one of the deadliest chemical weapons used in battle. Towards the end of the Great War, this gas killed and crippled thousands of soldiers. The first use in Ypres alone left up to 10,000 people dead, with many more injured.
Absorbed through the skin, gas masks offered no protection, and victims could take up to six weeks to die from mustard gas exposure.
Mustard Gas Beginnings
A chemist named Fritz Haber, a professor at the University of Karlsruhe, developed mustard gas. Although known for developing ammonia-based fertilizer and winning a Nobel Prize, his work had a dark side as he was instrumental in the research and development of chemical weapons.
Despite the devastating consequences of his work, Haber continued to promote the use of poison gas after the war. Along with others, he would go on to develop other deadly gases—hence, World War I is known in some quarters as the chemists’ war.
Fortunately, the story of mustard gas did not end there and has a brighter ending than might be thought.
A Search for a Cure
With the approach of World War II, the Allies feared a repeat of mustard gas attacks, so the race to find antidotes began. However, what researchers involved in this mission discovered led them into a very different battle.
Two Yale doctors studying medical records of soldiers exposed to mustard gas, Louis Goodman and Andrew Gilman, observed that many victims had a surprisingly low number of immune cells in their blood—cells that, if mutated, can develop into leukemia and lymphoma.
They theorized that if mustard gas could destroy normal white blood cells, it could likely destroy cancerous ones. From this theory, their research led to testing mustard gas on a patient with advanced lymphoma. Known only by his initials, J.D., this patient was considered a hopeless case, with tumours on his jaw preventing him from eating and swallowing. He was expected to die soon.
In 1942, Goodman and Gilman began injecting J.D. with a substance they called 'synthetic lymphocidal chemical,' which was, in fact, nitrogen mustard, referred to in official records only as 'substance X.'
Remarkably, the series of treatments began to work, and J.D.’s condition dramatically improved. This was a monumental moment in the history of medicine and marked the beginning of what we now know as chemotherapy.
Mustard Gas to Modern Medicine
After World War II, in the UK, chemist Professor Alexander Haddow, Director of the Chester Beatty Research Institute, worked on compounds able to block tumour growth and treat cancer. His research turned to mustard gas, and in 1948 he published ground breaking research showing exactly which parts of the nitrogen mustard molecule were needed to kill cancer cells. More importantly, he also discovered how to make the chemical less toxic but with increased potency in cancer-killing qualities.
Haddow began altering the components of the nitrogen mustard molecule, replacing or removing them. Significantly, his work on chlorine atoms, which rendered the molecule useless, showed that both chlorine atoms were needed to inhibit tumour growth. Haddow worked through the molecular puzzle, adapting the nitrogen mustard molecules to arrive at a chemical structure that would trigger the cancerous cell’s self-destruct mechanism—causing the cell to shut down and break apart, thereby destroying it. Further research identified the linked molecules as strands of DNA.
A New Era for Cancer
Haddow's work launched the start of a new era of cancer treatment—chemotherapy. All the drugs developed in the early days of research worked in the same basic way that Haddow described. Even in modern times, nitrogen mustard-derived chemotherapy is still used to treat some cancers.
Chemotherapy is not the last word in cancer treatment, and it is still, for many, a difficult and unpleasant experience. Research into improved targeted treatments continues, yet the story of its evolution remains a remarkable tale.
Mustard gas went from being a battlefield weapon of terror in the trenches to the frontline of cancer treatment. However, for J.D., the treatment came too late. Although his condition initially improved, he would die within a few months, unaware of the enormous contribution that his treatment would go on to have.
Featured image source: THE BATTLE OF THE SOMME, JULY-NOVEMBER 1916. By Brooke, John Warwick (Lieutenant) © IWM (Q 3995).
