December 2, 1943 The Surprising Origins of Chemotherapy

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

In ancient Greek mythology, Hercules poisoned 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, when tear gas grenades containing xylil bromide were used 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 World War 1.  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”.

russian-soldier-in-a-rubber-gas-mask-on-the-eastern-front-russia-during-K07NJ9

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 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 in 1937, by President Franklin Roosevelt: “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 she 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.

gettyimages-3276829-612x612
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 some 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.

bari_burning-ships

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 cancer and birth defects. To this day there is no antidote.

A thousand or more died outright in the bombing of December 2, 1943.  643 military service personnel were hospitalized for gas symptoms.  83 of them 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 chemical disaster at Bari was of uncertain nature.  Everyone with any knowledge of John Harvey’s secret cargo had been 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.

800px-Sidney_Farber_nci-vol-1926-300

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 went most heavily after rapidly dividing cells, such as white blood cells.

Alexander wondered if it might be useful in going after other types of 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, based on previous discoveries. The concept is 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.

To some, the 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 much.  Once a virtual death sentence, the American Cancer Society today estimates that one in 30 alive today are currently undergoing treatment or have done so, in the past.

April 22, 1915 From Trench Warfare to Modern Chemotherapy

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 the garlic smell, as the yellow-brown, heavier-than-air cloud creeps along the ground. 

According to Greek mythology, the malevolent centaur Nessus attempted to force himself upon Deianeira, wife of Hercules (Herakles).  Seeing this from across a river, Hercules shot Nessus with an arrow, poisoned by the venom of the Hydra.  In a final act of malice, the dying centaur convinced Deianeira his blood would make her husband, faithful for life.  Deianeira foolishly believed him, coming to realize her error only as her husband lay dying by the tainted blood of his victim.

Bauer_-_Hercules_Nessus_DeianiraBoth 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”, used to disperse a peasant revolt, in AD178.

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

1D7Imperial 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.

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

Gas

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.

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”.

07515e35e2b3066520041e37646e8831

Nazi Germany possessed some 45,000 tons of blister and nerve agents, though such weapons were rarely used against western adversaries.  The “Ostfront” – the apocalyptic race war pitting the Teuton against the Slavic states of the Soviet Union – 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”.

Animals in World War1

The official American policy toward chemical weapons was enunciated by President Franklin Roosevelt, in 1937.  

“ 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”. – Franklin D Roosevelt, in a letter to the United States Senate

None of the western allies resorted to chemical warfare in WW2, despite having accumulated over twice the chemical stockpile as 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.

main-qimg-6cec6b7ffb5cac17681e9f4e14d99d61-cGreat Britain possessed massive quantities of mustard, chlorine, Lewisite, Phosgene and Paris Green, awaiting retaliation should Nazi Germany resort to such weapons on the beaches of Normandy.  General Alan Brooke, Commander-in-Chief of the Home Forces, “[H]ad every intention of using sprayed mustard gas on the beaches” in the event of a German landing on the British home islands.

dog_gas_masks_02The Geneva Protocols on 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.

gettyimages-3276829-612x612

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.

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.

bari_burning-ships

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.

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 the garlic smell, as the yellow-brown, heavier-than-air cloud creeps along the ground.  Contact first results in redness and itching, 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.

Mustard_Gas-_Sketch_to_Illustrate_the_Effect_of_Mustard_Gas_on_Horses_Art.IWMART4942.jpgDeath comes in days or weeks.  Survivors are likely to suffer chronic respiratory disease and infections. DNA is 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 remained shrouded in secrecy.

At the time, the chemical disaster at Bari was all but unknown.  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.

148652682-1024x537.jpg

Dr. Alexander identified mustard as the responsible agent.   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.

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

800px-Sidney_Farber_nci-vol-1926-300
Dr. Sidney Farber, regarded by many as the “Father of Modern Chemotherapy”

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 estimates that there were 7,377,100 male cancer survivors in the United States as of January 1, 2016 and another 8,156,120, females.

 

A Trivial Matter
German chemist Albert Niemann discovered cocaine in 1859, and went on to document the poison effects of sulphur mustard around the time of the American Civil War. In 1913, British and German civilian researchers were accidentally exposed to mustard and had to be hospitalized. The German military obtained notes about the incident and promptly went about weaponizing the stuff.
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