December 2, 1943 The Surprising Origins of Chemotherapy

In the 12th century, Bernard of Chartres described a process of finding truth, in building on previous discoveries. The concept is best remembered in the words of Sir Isaac Newton, in 1675: “If I have seen further it is by standing on the shoulders of Giants”.


Ancient Greek mythology depicts Hercules, poisoning arrows with the venom of the Hydra. Both sides in the battle for Troy used poisoned arrows, according to the Iliad and the Odyssey of Homer.   Alexander the great encountered poison arrows and fire weapons in the Indus valley of India, in the fourth century, BC.  Chinese chronicles describe an arsenic laden soul-hunting fog produced by the burning of toxic vegetation, used to disperse a peasant revolt in AD178.

“Soul-hunting fog”.

Yikes

The French were the first to use poison weapons in the modern era in August 1914, firing tear gas grenades containing xylil bromide against German forces in the first month of the Great War.

Imperial Germany was first to give serious study to chemical weapons

of war, early experiments with irritants taking place at the battle of Neuve-Chapelle in October 1914, and with tear gas at Bolimów on January 31, 1915 and again at Nieuport, that March.

The first widespread use of poison gas, in this case chlorine, came on April 22, 1915, at the second battle of Ypres.

The story of gas warfare is inextricably linked with that of WW1.  124,000 tons of the stuff was produced by all sides by the end of the war, accounting for 1,240,853 casualties, including the agonizing death of 91,198.

WW1 gas attack in Flanders

Had the war continued into 1919, technological advances promised new and fresh hell, unimaginable to the modern reader.

Today we think of chemical agents in WW2 as being limited to the death camps of the Nazis, but such weapons were far more widespread.  The Imperial Japanese military frequently used vesicant (blister) agents such as Lewisite and mustard gas against Chinese military and civilians, and in the hideous “medical experiments” conducted on live prisoners at Unit 731 and Unit 516.  Emperor Hirohito personally authorized the use of toxic gas during the 1938 Battle of Wuhan, on no fewer than 375 occasions.

Japanese, Gas Artillery

The Italian military destroyed every living creature in its path during the 1936 Colonial war with Ethiopia, in what Emperor Haile Selassie called “a fine, death-dealing rain”.

Nazi Germany possessed some 45,000 tons of blister and nerve agents, though such weapons were rarely used against western adversaries.  The “Ostfront” – the battle on the eastern front – was a different story.  Russian resistance fighters and Red Army soldiers were attacked, most notably during the assault on the catacombs of Odessa in 1941, the 1942 siege of Sebastopol, and the nearby caves and tunnels of the Adzhimuskai quarry, where “poison gas was released into the tunnels, killing all but a few score of the (3,000+) Soviet defenders”.

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None of the western allies resorted to chemical warfare in WW2, despite having accumulated over twice the chemical stockpile as that of Nazi Germany.  The policy seems to have been one of “mutually assured destruction”, where no one wanted to be first to go there, but all sides reserved the option.  Great Britain possessed massive quantities of mustard, chlorine, Lewisite, Phosgene and Paris Green, awaiting the retaliatory strike should Nazi Germany resort to such weapons on the beaches of Normandy. 

General Alan Brooke, Commander-in-Chief of the Home Forces, said he “[H]ad every intention of using sprayed mustard gas on the beaches” in the event of a German landing on the British home islands.

The official American policy toward chemical weapons was enunciated by President Franklin Roosevelt, in 1937: “I am doing everything in my power to discourage the use of gases and other chemicals in any war between nations. While, unfortunately, the defensive necessities of the United States call for study of the use of chemicals in warfare, I do not want the Government of the United States to do anything to aggrandize or make permanent any special bureau of the Army or the Navy engaged in these studies. I hope the time will come when the Chemical Warfare Service can be entirely abolished”.

The Geneva Protocols of 1925 banned the use of chemical weapons, but not their manufacture, or transport.  By 1942, the U.S. Chemical Corps employed some 60,000 soldiers and civilians and controlled a $1 Billion budget.

In August 1943, Roosevelt authorized the delivery of chemical munitions containing mustard gas, to the Mediterranean theater. Italy surrendered in early September, changing sides with the signing of the armistice of Cassibile.

The liberty ship SS John Harvey arrived at the southern Italian port of Bari in November, carrying 2000 M47A1 mustard gas bombs, each containing 60 to 70-pounds of sulfur mustard.

Bari was packed at the time, with ships waiting to be unloaded.  It would be days before stevedores could get to her. Captain John Knowles wanted to inform port authorities of his deadly cargo and request that it be unloaded immediately, but secrecy prevented him from doing so. As it was, John Harvey was still waiting to be unloaded, on December 2.

For Luftwaffe Generalfeldmarschall Albert Kesselring, the traffic jam at Bari was an opportunity to slow the advance of the British 8th army on the Italian peninsula.

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Air raid on Bari, December 2, 1943

The “Little Pearl Harbor” began at 7:25PM when 105 Junkers JU-88 bombers came out of the East.   The tactical surprise was complete, and German pilots were able to bomb the harbor with great accuracy. Two ammunition ships were first to explode, shattering windows 7 miles away. A bulk gasoline pipeline was severed, as a sheet of burning fuel spread across the harbor, igniting those ships left undamaged.

43 ships were sunk, damaged or destroyed including John Harvey, which erupted in a massive explosion.  Liquid sulfur mustard spilled into the water, as a cloud of toxic vapor blew across the port and into the city.

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Mustard gas is a cytotoxic agent, capable of entering the system via skin, eyes and respiratory tract and attacking every cell type with which it comes into contact. First comes a garlic odor as the yellow-brown, heavier-than-air cloud creeps along the ground.  Contact results in redness and itching at first, resulting 12-24 hours later in excruciating, untreatable blisters on exposed areas of the skin.  Sufferers are literally burned inside and out as mucous membranes are stripped away from the eyes, nose and respiratory tract.

Death comes in days or weeks.  Survivors are likely to develop chronic respiratory disease and infections. DNA is permanently altered, often resulting in certain cancers and birth defects. To this day there is no antidote.

A thousand or more died outright in the bombing.  643 military service personnel were hospitalized for gas symptoms.  83 of those were dead, by the end of the month.  The number of civilian casualties is unknown.  The whole episode was shrouded in secrecy and remains to this day, one of the lesser-known chapters of World War 2.

At the time, the nature of the chemical disaster at Bari was uncertain.  Everyone with any knowledge of John Harvey’s secret cargo was killed in the explosion.  Lieutenant-Colonel Stewart Francis Alexander, an American physician from New Jersey, was sent by the Deputy Surgeon General of the US Army to find out what happened.

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It was Dr. Alexander who figured out the responsible agent was mustard, and where the stuff had come from.   In the process of testing, Dr. Alexander noticed the unknown agent first went after rapidly dividing cells, such as white blood cells.

Alexander wondered if it might be useful in going after other rapidly dividing cells. Like cancer.

Based on Dr. Alexander’s field work, Yale pharmacologists Louis Goodman and Alfred Gilman developed the first anti-cancer chemotherapy drug, in the treatment of lymphoma. 

In the 12th century, Bernard of Chartres described a process of finding truth, in building on previous discoveries. The concept is best remembered in the words of Sir Isaac Newton, in 1675: “If I have seen further it is by standing on the shoulders of Giants”.

Dr. Sidney Farber of Boston built on this earlier work, producing remission in children with acute Leukemia using Aminopterin, an early precursor to Methotrexate, a chemotherapy drug still in use, today.

Writers have labeled SS John Harvey a Savior of Millions, due to the vessel’s role in the pioneering era of modern chemotherapy drugs.

The claim may be a bit of an exaggeration, but not entirely so.  The American Cancer Society today estimates cancer survivors in the range of 16.9 million.