The Chemists’ Wars: The Origin Story of Chemistry, Episode 2

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<v SPEAKER_02>This is Chain Reaction, a podcast from the American Chemical Society, where we link chemistry's past to its future.

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<v SPEAKER_02>I'm your host, Margo Wall.

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<v SPEAKER_02>And I'm Sam Jones.

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<v SPEAKER_01>So, Margo, where we left off in the last episode, chemistry had transformed from more of an artisan practice to a quest to manipulate materials like transforming metals into gold, and finally into a more established field with laws explaining how chemicals act.

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<v SPEAKER_01>So, by the late 1800s, chemistry was now an industry, dominated by things like producing dyes.

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<v SPEAKER_01>There were societies and journals to share knowledge, and governments were interested in how chemistry could help them achieve their goals, particularly in the realm of furthering and protecting national interests.

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<v SPEAKER_01>And that is the theme of this episode: war.

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<v SPEAKER_01>Alright, Marco, take it away.

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<v SPEAKER_01>Okay, Sam.

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<v SPEAKER_02>So sometimes chemistry has the ability to change war.

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<v SPEAKER_02>Gunpowder was discovered in 9th century China, and weapons became speedier, more explosive, and deadlier.

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<v SPEAKER_02>But sometimes war changed chemistry, pushing chemists to create new ways to injure the enemy and protect the troops.

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<v SPEAKER_02>This was especially true during the two world wars.

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<v SPEAKER_03>This is chemical warfare.

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<v SPEAKER_03>It kills the unprotected and contaminates widespread areas so that no human being, unaided by protective devices, can move into it and remain unharmed.

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<v SPEAKER_02>The act of using chemistry, primarily that of toxic gases to do spooky damage at a distance, propelled a great expansion of the chemical industry.

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<v SPEAKER_02>While Germans could convert their impressive dye factories into suppliers of new weapons, places like the U.S.

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<v SPEAKER_02>would need to pool talent from academia and from government agencies, like, believe it or not, the Bureau of Mines.

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<v SPEAKER_02>Did not know the Bureau of Mines was a thing.

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<v SPEAKER_02>Yeah.

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<v SPEAKER_02>Alison McManus is an assistant professor in the Department of History of Science and Technology at Johns Hopkins University.

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<v SPEAKER_02>She's a historian of chemical warfare, and in today's episode, we talk about how chemists became arguably as important as soldiers in the wars of the 20th century.

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<v SPEAKER_06>It's an interesting question.

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<v SPEAKER_06>So if you were to ask me when did chemical warfare begin, there's three possible answers.

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<v SPEAKER_06>The first is chemical warfare has been going on as long as warfare has existed, right?

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<v SPEAKER_06>You can look at ancient precedents like poisoned arrows, slightly less ancient precedents like gunpowder, for instance.

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<v SPEAKER_06>So there's that argument to be made.

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<v SPEAKER_06>Second possibility is World War One.

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<v SPEAKER_06>So you could say chemical warfare began in the fall of 1914.

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<v SPEAKER_06>That's essentially in the first few months of World War One.

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<v SPEAKER_06>And that was when the French and the Germans experimented with using tear gases in battle.

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<v SPEAKER_06>But it wasn't particularly effective.

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<v SPEAKER_06>And in some cases, it was so ineffective that the other side didn't even know that this was going on.

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<v SPEAKER_06>So most of the time, historians would say that chemical warfare began on April 22nd, 1915, about 6 p.m.

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<v SPEAKER_06>European Central Time.

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<v SPEAKER_06>And that was when Fritz Haber and his staff released chlorine gas clouds over the battlefield near the Belgian town of Ypres.

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<v SPEAKER_06>So even though chemistry has been important for war since time immemorial, World War I is really a turning point in the relationship between chemistry and war.

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<v SPEAKER_02>Can you tell me more about Fritz Haber and the chlorine gas that he ended up releasing?

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<v SPEAKER_02>Yes, absolutely.

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<v SPEAKER_06>Fritz Haber is easily one of the most famous chemists in history, not always for good reason.

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<v SPEAKER_06>He first became famous because he solved the problem of nitrogen fixation, basically enabling Germany to produce nitrates for fertilizer.

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<v SPEAKER_06>However, relatively soon afterwards, he became interested in the problem of chemical warfare.

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<v SPEAKER_06>And he was actually on a committee that the German government set up during World War I to deal with this problem of using poison gas in battle.

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<v SPEAKER_06>And since they had experimented with tear gas, and that wasn't particularly effective, at least not initially, Haber had the idea of weaponizing chlorine gas.

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<v SPEAKER_06>And he chose chlorine gas for a couple of reasons.

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<v SPEAKER_06>One is that it was easily producible and very widely produced.

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<v SPEAKER_06>It can be used to generate quite a few different industrial chemicals.

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<v SPEAKER_06>So there's that.

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<v SPEAKER_06>And then in addition, chlorine gas is denser than air.

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<v SPEAKER_06>Why is that important?

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<v SPEAKER_06>They were trying to solve the stalemate of trench warfare, and they knew that an effective chemical weapon would need to be something that could get into the trenches which tended to be below the ground.

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<v SPEAKER_02>So at the time, I know that Germany wasn't the only one that was coming up with different chemical agents, that there was this race going on between different countries.

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<v SPEAKER_02>Can you give me a play-by-play of that?

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<v SPEAKER_06>So the very first chemical weapons that were used in World War I were tear gases, which were relatively ineffective.

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<v SPEAKER_06>The second, chlorine gas clouds.

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<v SPEAKER_06>And importantly, these were weapons released from cylinders.

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<v SPEAKER_06>They were not in artillery shells.

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<v SPEAKER_06>So those were the first two important developments.

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<v SPEAKER_06>But what the German army found is that the Entente powers were able to develop protective measures pretty quickly, gas masks primarily.

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<v SPEAKER_06>And so although the first chlorine gas attack was quite effective, they experienced diminishing returns over time.

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<v SPEAKER_06>So now what?

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<v SPEAKER_06>Well, the chemists went back to the drawing board.

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<v SPEAKER_06>And as with so many things, they often started with literature searches.

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<v SPEAKER_06>There being very, very specific requirements for a chemical weapon.

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<v SPEAKER_06>It's not sufficient that a compound be extremely poisonous.

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<v SPEAKER_06>It needs to check off a whole lot of boxes.

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<v SPEAKER_06>It needs to be easy to produce, cheap to produce.

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<v SPEAKER_06>It should have high vapor pressure.

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<v SPEAKER_06>It should be stable in storage, easy to aerosolize, and so on.

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<v SPEAKER_06>So fast forward to 1917, the Germans introduced sulfur mustard.

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<v SPEAKER_06>This was often referred to as the king of war gases.

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<v SPEAKER_06>It's extremely famous, extremely infamous, really.

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<v SPEAKER_06>It's a blister agent.

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<v SPEAKER_06>It affects the lungs.

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<v SPEAKER_06>It also affects the skin.

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<v SPEAKER_06>And this really changed chemical warfare because now soldiers had to worry about wearing gas masks as well as ensuring that every inch of their body was covered.

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<v SPEAKER_06>Now, interestingly enough, after the Germans introduced sulfur mustard, it took the British only about three days to analyze the sample and figure out what it was.

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<v SPEAKER_06>But it took them about another year to be able to produce it at scale.

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<v SPEAKER_06>And we see this happen quite a bit.

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<v SPEAKER_06>Again, it's the game of leapfrog, right?

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<v SPEAKER_06>One side introduces a novel agent, the other side captures a sample, analyzes it, and works to develop countermeasures, works to produce the agent in their country as well.

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<v SPEAKER_02>So during World War I, I'm guessing that there were a lot of changes to the industry of chemistry in that they were trying to make a lot of stuff really fast.

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<v SPEAKER_02>Yes.

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<v SPEAKER_02>Who was making all of these explosives and chemical agents, kind of all of the chemical stuff that was being used in the war?

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<v SPEAKER_06>It's absolutely right that World War I dramatically transformed the chemical industry.

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<v SPEAKER_06>And it dramatically transformed international competition in the chemical industry too.

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<v SPEAKER_06>Because at the beginning of the war, the Germans were clearly dominant in this field.

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<v SPEAKER_06>And as a result of World War I, other nations, chiefly the United States, caught up.

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<v SPEAKER_06>So in Germany, the chemical firms Bosf and Bayer were particularly involved in the development of chemical weapons.

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<v SPEAKER_06>In the United States, if you're talking about chemical weapons and explosives together, Dow and DuPont were both involved.

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<v SPEAKER_06>And we do know that Dow was producing mustard gas at one of its factories as well.

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<v SPEAKER_06>And there was one incident where unfortunately there was an explosion and three workers died there as a result.

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<v SPEAKER_06>A lot of chemical firms were in fact comparatively unwilling to undertake mass production of chemical weapons agents because they were more dangerous to manufacture even than explosives.

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<v SPEAKER_06>And so as it happened in the United States, even though the government relied on private industry, they also had their own factories, what later became Edgewood Arsenal, for instance.

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<v SPEAKER_02>Oh, that is like right by where I grew up.

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<v SPEAKER_02>Yeah.

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<v SPEAKER_02>Like really close.

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<v SPEAKER_02>That's kind of what Yeah was founded during World War I.

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<v SPEAKER_02>Right.

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<v SPEAKER_02>In Edwood, Maryland.

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<v SPEAKER_02>That's right.

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<v SPEAKER_02>Are there ever like descriptions from people who experienced these chemical agents, like what it felt like, how kind of torturous they were?

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<v SPEAKER_06>Yeah, absolutely.

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<v SPEAKER_06>And you see this very often in interwar poetry and visual arts.

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<v SPEAKER_06>There's a really, really famous painting by John Singer Sargent called Gast, where you can see a whole lot of British soldiers that have been exposed to mustard gas.

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<v SPEAKER_06>They have bandages over their eyes.

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<v SPEAKER_06>Mustard gas is very hard on the eyes.

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<v SPEAKER_06>It can cause temporary blindness.

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<v SPEAKER_06>And they're trying to lead each other back to safety.

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<v SPEAKER_06>So chemical warfare definitely had a strong impact on the soldiers that it affected.

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<v SPEAKER_06>And, you know, by extension, the publics that they returned home to.

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<v SPEAKER_02>Was there an argument that chemists or generals would make for chemical weapons versus guns or bombs or other means of warfare?

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<v SPEAKER_06>Yeah, absolutely.

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<v SPEAKER_06>So you see these arguments made on both sides of the war.

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<v SPEAKER_06>So those that were in charge of the American Chemical Warfare Service sometimes suggested that certain chemical weapons were more humane than conventional weapons because they were more liable to cause temporary injury and gave soldiers more of an opportunity to recover from their injuries.

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<v SPEAKER_06>These were not popular arguments, I have to say.

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<v SPEAKER_06>In general, the American public was not persuaded.

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<v SPEAKER_06>So the 1925 Geneva Protocol was a very important attempt to ban the use of chemical weapons in war.

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<v SPEAKER_06>It wasn't the first and it wasn't the last and it wasn't the most successful, but it was an important attempt.

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<v SPEAKER_06>Again, it banned the use in war of asphyxiating or deleterious gases.

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<v SPEAKER_06>Um it didn't ban stockpiling, didn't ban research, but nevertheless it was an important step forward.

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<v SPEAKER_06>There's a lot of optimism attached to this treaty at the time.

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<v SPEAKER_06>And then that gradually fell away in part because the United States, a very important potential party to the treaty, signed it but did not ratify it.

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<v SPEAKER_06>So there were a lot of veterans groups that were lobbying Congress not to ratify the treaty.

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<v SPEAKER_06>You also have to look at the American Chemical Society.

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<v SPEAKER_06>So the American Chemical Society was very involved in chemical warfare research.

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<v SPEAKER_06>I've read one statistic that about 500 members of the ACS had worked for the Chemical Warfare Service during World War I.

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<v SPEAKER_06>Not coincidentally, the ACS was also celebrating its 50th anniversary around the time of the debate on the ratification of the Geneva Protocol.

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<v SPEAKER_06>The organization was already primed to think about their role in American society.

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<v SPEAKER_06>And by and large, they thought that the treaty to ban the use of chemical weapons in war would be rather ineffective.

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<v SPEAKER_06>And theirs was also an argument based on preparedness.

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<v SPEAKER_06>They thought that it would be better for the United States to maintain a strong chemical industry and to maintain chemical weapons stockpiles.

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<v SPEAKER_06>So ACS members lobbied senators, and they were so effective that there was never even a vote.

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<v SPEAKER_06>The administration just took the ratification off the floor of the Senate.

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<v SPEAKER_06>And it was not until 50 years later that the United States finally ratified the Geneva Protocol.

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<v SPEAKER_02>There's quite a bit of time between, or not, depending on how you look at it, between World War I and World War II.

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<v SPEAKER_02>Yeah.

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<v SPEAKER_02>Were there still developments going on in the chemical warfare space, like perhaps preparing for a next war?

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<v SPEAKER_06>So the most important research development that happened in the interwar period, you know, unfortunately it happened in Nazi Germany.

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<v SPEAKER_06>In the 1930s, a German chemist by the name of Gerhard Schroeder, who was working for the chemical conglomerate, IG Farben, developed what we now call the G-series nerve agents, Tabin and Saren.

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<v SPEAKER_06>And these were kept a secret until the last few weeks of the European war.

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<v SPEAKER_06>And as the European war looked sort of ever more likely, you see nations that would be fighting on the side of the Allied powers putting more and more effort into chemical weapons and more effort into devising effective protective measures, passing out gas masks to all of their civilians.

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<v SPEAKER_06>I think it was the British government actually developed a Mickey Mouse gas mask for children to make them just a little bit less scared and more likely to have good gas discipline.

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<v SPEAKER_06>There's also efforts to develop gas masks for horses or protective equipment that would go over cribs and so on.

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<v SPEAKER_02>So then that brings us into World War II.

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<v SPEAKER_02>I think, you know, a lot of people, including myself, when we think of World War II, think of Blitzkrieg and naval warfare and the atomic bomb.

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<v SPEAKER_02>Was chemical warfare no longer a strategy?

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<v SPEAKER_06>So oftentimes you see World War I referred to as the Chemists' War, World War II referred to as the physicists' war.

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<v SPEAKER_06>One of the things that I want people to understand is just how many physicists that worked on World War I era problems would be troubled by that designation, and just how many chemists that worked on research problems relevant to World War II would also be troubled by that designation.

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<v SPEAKER_06>The first thing I'll say is that chemical warfare did occur in World War II, but it occurred in the Asian theater.

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<v SPEAKER_06>The Japanese Imperial Army used chemical weapons in China on many different occasions.

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<v SPEAKER_06>Even in the European theater, armies wanted to be prepared to meet chemical weapons attacks.

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<v SPEAKER_06>So the Germans, the British, and the Americans, the Russians, and the list goes on, all worked on chemical weapons RD in World War II.

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<v SPEAKER_06>This is where you get Agent Orange jointly developed by the US and the UK.

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<v SPEAKER_06>It was originally developed for use against German crops and Japanese crops, not deployed in that conflict.

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<v SPEAKER_06>Of course, infamously deployed by the United States in Vietnam.

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<v SPEAKER_02>I see.

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<v SPEAKER_02>How did the chemicals used in warfare differ from the chemicals used in the extermination camps by the Nazis?

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<v SPEAKER_06>So the chemicals used in war, it's a long list.

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<v SPEAKER_06>There's tear gases, there's sulfur mustard, there's arsenicals, and so on.

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<v SPEAKER_06>When you're talking about which chemical compounds were used as weapons of the Holocaust specifically, you're generally talking about carbon monoxide and hydrogen cyanide-based insecticide called Zyklon B, which incidentally Fritz Haber also worked on during the interwar period, although he was not at all intending for these insecticides to be used the way that the Nazi regime eventually used them.

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<v SPEAKER_06>We do know that the Nazi regime used some of these chemicals to murder members of Haber's extended family.

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<v SPEAKER_06>Back to your question about the comparison between these two kinds of agents.

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<v SPEAKER_06>There were attempts to generate hydrogen cyanide-based weapons in World War One.

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<v SPEAKER_06>But in general, they weren't favored because the warfare was occurring under open air and the chemical compound is much more toxic in an enclosed area, which is a fact that the Nazi regime um very much exploited.

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<v SPEAKER_02>Um these two world wars changed how chemistry was done.

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<v SPEAKER_06>What was the legacy of chemical warfare for the discipline of chemistry, in other words?

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<v SPEAKER_06>Exactly.

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<v SPEAKER_06>Yeah.

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<v SPEAKER_06>Yep.

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<v SPEAKER_06>Yeah.

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<v SPEAKER_06>One answer that I'll give is that chemical warfare changed the public image of chemistry.

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<v SPEAKER_06>And in some ways, I'm not sure that chemistry as a discipline has recovered from that.

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<v SPEAKER_06>It's a discipline that's strongly associated with war.

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<v SPEAKER_06>And I think chemical warfare has prompted chemists to take a closer look and in some cases a hard look at their own history.

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<v SPEAKER_06>That's one powerful legacy.

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<v SPEAKER_01>What really struck me during this interview was the reuse of chemicals that started off having one purpose, but then were used for something else, like a fertilizer or an insecticide being co-opted as a chemical weapon, or vice versa.

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<v SPEAKER_02>Yeah, totally.

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<v SPEAKER_02>There are only so many chemicals that nature makes or that we have made to work with, especially during this time period.

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<v SPEAKER_02>And that co-opting actually happened during World War II as well.

00:19:10.079 --> 00:19:16.400
<v SPEAKER_02>But this time it was to protect from the foreign land itself and the flora and fauna within.

00:19:16.640 --> 00:19:18.240
<v SPEAKER_02>Here's a clip from a U.S.

00:19:18.400 --> 00:19:20.960
<v SPEAKER_02>Army training film from 1944.

00:19:21.359 --> 00:19:26.319
<v SPEAKER_05>Behind the beachheads of the Pacific lies the jungle, and in it, the enemy.

00:19:26.640 --> 00:19:32.559
<v SPEAKER_05>The sudden danger of an insect fight, the fierceness of the heat, the disease of a polluted swamp.

00:19:33.039 --> 00:19:37.920
<v SPEAKER_05>Here is where the silence presses in on a man, then suddenly breaks.

00:19:47.119 --> 00:19:52.640
<v SPEAKER_02>Yes, especially a disease carried by a pesky insect that sucks.

00:19:53.039 --> 00:19:54.640
<v SPEAKER_02>This is from another U.S.

00:19:54.720 --> 00:19:59.440
<v SPEAKER_02>government film, The Winged Scourge, made by Disney in 1943.

00:19:59.680 --> 00:20:01.440
<v SPEAKER_04>Public enemy number one.

00:20:04.960 --> 00:20:07.119
<v SPEAKER_04>This man is healthy and happy.

00:20:07.359 --> 00:20:11.839
<v SPEAKER_04>Little does he suspect he's to be the victim of this bloodthirsty vampire.

00:20:12.079 --> 00:20:18.000
<v SPEAKER_04>In all probability, this man will not die, but neither will he truly be alive.

00:20:20.079 --> 00:20:23.920
<v SPEAKER_01>This man will not die, but neither will he truly be alive.

00:20:24.480 --> 00:20:27.359
<v SPEAKER_01>Oh, that that is quite the terrifying line.

00:20:27.599 --> 00:20:31.759
<v SPEAKER_01>And uh, I, like so many others, really hate mosquitoes.

00:20:32.000 --> 00:20:35.839
<v SPEAKER_01>80s, anophiles, I don't care what genus, no thank you.

00:20:36.000 --> 00:20:38.000
<v SPEAKER_01>I'm total bug bait.

00:20:38.240 --> 00:20:44.720
<v SPEAKER_02>Uh Sam, I did study their sense of smell in a former life and still not endeared to them.

00:20:45.039 --> 00:20:50.880
<v SPEAKER_02>But they are important little creatures that have a massive impact on us as humans.

00:20:51.200 --> 00:20:53.519
<v SPEAKER_02>Even more so a century ago.

00:20:53.759 --> 00:21:06.559
<v SPEAKER_02>So for the second part of this episode, I talked with Karen Masterson, a journalism professor at the University of Richmond who wrote The Malaria Project, the US government's secret mission to find a miracle cure.

00:21:06.799 --> 00:21:20.319
<v SPEAKER_02>We chatted about the race to find a prophylactic and treatment for this mosquito-borne illness that devastated troops during the world wars, and how investment in this race kick-started American pharmaceutical companies.

00:21:20.559 --> 00:21:26.400
<v SPEAKER_02>And we begin with the state of the pharmaceutical industry right after World War One.

00:21:30.720 --> 00:21:38.400
<v SPEAKER_00>So it's interesting to start there because after World War I, Germany, you know, was recovering from the Versailles Treaty.

00:21:38.559 --> 00:21:40.000
<v SPEAKER_00>Germany had lost all its patents.

00:21:40.160 --> 00:21:44.160
<v SPEAKER_00>Germany was really the leader in all things chemistry, right?

00:21:44.240 --> 00:21:53.759
<v SPEAKER_00>It had its big chemical production plants, all located along the same river, had bear industries, which was the biggest pharmaceutical company in the world.

00:21:53.920 --> 00:22:10.799
<v SPEAKER_00>All these companies, they decided that the only way to recover from the terms of the Treaty was to create a conglomerate and do some price fixing and work with each other so that when they combined all of their libraries, they had thousands and thousands of formula.

00:22:11.119 --> 00:22:17.599
<v SPEAKER_00>So they had everything that they needed and they just were developing know-how and skills, unlike any other country.

00:22:17.759 --> 00:22:20.720
<v SPEAKER_00>And certainly they were they were light years ahead of the United States.

00:22:21.839 --> 00:22:28.480
<v SPEAKER_02>So what were some of the diseases that were really prevalent in World War II and that were a problem?

00:22:28.799 --> 00:22:38.319
<v SPEAKER_00>Yeah, berry berry was a problem because that was a vitamin deficiency disease called filoriasis that troops did pick up in the South Pacific.

00:22:38.480 --> 00:22:52.079
<v SPEAKER_00>The fileri is the type of worm, and once it's in the body, it grows large and it gums up the lymphatic system and causes gross deformation, especially of ankles, breasts, scrota.

00:22:52.480 --> 00:22:53.759
<v SPEAKER_00>So that was a concern.

00:22:53.920 --> 00:22:57.279
<v SPEAKER_00>Um dysentery, big concern, carried by flies.

00:22:57.519 --> 00:23:04.559
<v SPEAKER_00>Lice carry typhus, um, VD Venereal disease venereal disease was the one that they worried about most.

00:23:04.960 --> 00:23:17.279
<v SPEAKER_00>And in a lot of these theaters, they were developing strategies to contain sexually transmitted diseases, only to realize that it didn't matter because malaria was the number one problem.

00:23:17.759 --> 00:23:23.440
<v SPEAKER_00>In places like Guadalcanal, 10 men fell to every one who fell because of a bullet.

00:23:23.599 --> 00:23:29.599
<v SPEAKER_00>There are 10 casualties, and I don't mean casualties in terms of death, I mean casualties in inability to fight.

00:23:29.839 --> 00:23:30.960
<v SPEAKER_00>You mean from sickness.

00:23:31.200 --> 00:23:32.559
<v SPEAKER_00>From sickness, from malaria.

00:23:33.119 --> 00:23:34.079
<v SPEAKER_00>But they're not dead.

00:23:34.319 --> 00:23:41.759
<v SPEAKER_00>But yeah, okay, and that they're not dead is a problem because they're too sick to fight and they have to be taken care of.

00:23:42.000 --> 00:23:45.200
<v SPEAKER_00>They need a hospital bed, they need constant care.

00:23:45.680 --> 00:23:47.200
<v SPEAKER_00>Malaria doesn't go away in a week.

00:23:47.359 --> 00:23:52.319
<v SPEAKER_00>Malaria, depending on the person, depending on the conditions, lasts for weeks, and then it comes back.

00:23:52.640 --> 00:23:58.480
<v SPEAKER_00>The number one medical priority was to find synthetic quinine.

00:23:58.880 --> 00:24:07.440
<v SPEAKER_00>And Germany really had the advantage at first because quinine came from secona tree bark, and sarcona trees are really fickle and hard to grow.

00:24:07.599 --> 00:24:10.480
<v SPEAKER_00>There has to be a certain level of humidity and heat.

00:24:10.559 --> 00:24:20.880
<v SPEAKER_00>And so Java, like in Indonesia, was the perfect climate, and the British controlled and the Dutch controlled those syncona tree plantations.

00:24:21.119 --> 00:24:31.440
<v SPEAKER_00>So Germany thought, okay, if they could come up with a replacement, a synthetic version of quinine, they would have a blockbuster drug as big as bear aspirin.

00:24:31.599 --> 00:24:38.240
<v SPEAKER_00>So they looked to what some people call the father of medical chemistry, Paul Ehrlich.

00:24:38.960 --> 00:24:41.039
<v SPEAKER_00>He was kind of considered a loon.

00:24:41.279 --> 00:24:47.359
<v SPEAKER_00>But he came to the Koch Institute with a PhD in dyeing germs.

00:24:47.759 --> 00:24:53.039
<v SPEAKER_00>Actual color dye dyes to color germs and cells.

00:24:53.440 --> 00:24:58.000
<v SPEAKER_00>Methylene blue had a particular affinity to malaria microbes.

00:24:58.240 --> 00:25:05.759
<v SPEAKER_00>And he had this idea well, if I attach a poisonous side chain, like a methyl group, then maybe it could work as a poison pill.

00:25:06.079 --> 00:25:12.319
<v SPEAKER_02>You put it with the dye, the dye goes, finds the parasites, and then the methyl side chain kills the parasite.

00:25:12.480 --> 00:25:12.880
<v SPEAKER_02>Yeah, yeah.

00:25:13.119 --> 00:25:13.359
<v SPEAKER_02>Okay.

00:25:13.680 --> 00:25:16.799
<v SPEAKER_00>So it worked actually beautifully in canaries.

00:25:16.960 --> 00:25:22.640
<v SPEAKER_00>So he was turning these birds blue and he was seeing that he the infections were being killed off.

00:25:22.720 --> 00:25:38.160
<v SPEAKER_00>So then he tested it in humans at an asylum in Dusseldorf and learned that yes, he could reduce the number of parasites in the blood, but it turned patients blue and it was quite toxic and you couldn't use it.

00:25:38.319 --> 00:25:39.599
<v SPEAKER_00>But the idea stuck.

00:25:39.759 --> 00:25:55.519
<v SPEAKER_00>So the Germans took the smethylene-blue idea and they added amino side change as the poison and they came up with what was called 8 amino quinilines because the base molecule resembled quinine and it was toxic in some people and they didn't understand why.

00:25:55.680 --> 00:26:04.799
<v SPEAKER_00>And so they you know they kept moving the molecules around and then they they moved this yellow dye and they came up with something called adebrin, but it turns people yellow and it's makes people sick.

00:26:04.960 --> 00:26:15.759
<v SPEAKER_00>And what the Germans knew was that you start off on low doses and you let people get to that blood absorption level at a slow pace, and then once they reach it, they're protected from malaria.

00:26:16.000 --> 00:26:19.839
<v SPEAKER_00>And so they, their troops, were using adobrine in a really effective way.

00:26:20.079 --> 00:26:26.880
<v SPEAKER_00>We were making atorin for our troops, and it was a catastrophe because the dosing was wrong.

00:26:27.119 --> 00:26:42.640
<v SPEAKER_00>There's this one awful battle in Tunisia where the adobrin just arrived to protect the troops as they made their move on Tunis and they just started emptying their bowels and throwing up like on the hillsides.

00:26:43.039 --> 00:26:46.160
<v SPEAKER_00>The Americans were really far behind and had to catch up.

00:26:46.480 --> 00:27:01.200
<v SPEAKER_00>The situation with malaria first had to unfold in order for the War Department to take it seriously enough to start recruiting qualified scientists from other disciplines to actually tackle this problem.

00:27:01.680 --> 00:27:08.079
<v SPEAKER_00>And the United States decides quinine's better, we have plenty of quinine coming from Java through the Dutch and the British.

00:27:08.240 --> 00:27:18.160
<v SPEAKER_00>Then Japan blockades Java, shuts down access to all that quinine, and there just isn't enough in storage for the war.

00:27:18.319 --> 00:27:24.960
<v SPEAKER_00>So, like public health officials are hollering at the war department, we have to get going on this project because we need to find a drug.

00:27:25.119 --> 00:27:39.359
<v SPEAKER_00>And it takes Guadalcanal and the disaster on Guadalcanal, because everyone got malaria there, for the war department to finally buy in, give these scientists the money that they'd been asking for so that they could ramp up this project.

00:27:39.519 --> 00:27:53.279
<v SPEAKER_00>And so the malaria project becomes the number one medical priority of the Office of Scientific Research and Development, which was the umbrella organization for all science projects of World War II, including the Manhattan Project, right?

00:27:53.599 --> 00:28:02.880
<v SPEAKER_00>So a lot of people today call the malaria project the Manhattan Project of medicine because it siphoned all these scientists from all these other disciplines because it was such a problem.

00:28:03.119 --> 00:28:08.400
<v SPEAKER_00>So um parasitologists, entomologists, because it's mosquitoes, right?

00:28:08.640 --> 00:28:15.920
<v SPEAKER_00>Chemists, especially, probably, in my view, the most important were the chemists because they needed the chemists to come up with a drug.

00:28:16.240 --> 00:28:18.000
<v SPEAKER_02>What did they do with that money?

00:28:18.079 --> 00:28:20.319
<v SPEAKER_02>How did they try to solve the malaria problem?

00:28:20.640 --> 00:28:24.319
<v SPEAKER_00>So the malaria project was to find a drug, right?

00:28:24.480 --> 00:28:41.920
<v SPEAKER_00>And so, based on these formula that had come out of Germany, the eight aminoquinolines, Adabran, they started rotating side chains around central molecules, and they were making thousands of versions of these chemicals, and they tested them on animals first.

00:28:42.079 --> 00:28:54.559
<v SPEAKER_00>If something made it through the bird malaria, through the dog toxicity, then they would move them into humans at state hospitals and prisons because they needed clinical material.

00:28:54.960 --> 00:28:58.400
<v SPEAKER_00>That's what they called people who were in their studies.

00:28:58.559 --> 00:29:04.480
<v SPEAKER_00>There were thousands of test subjects, tens of thousands of test subjects.

00:29:04.960 --> 00:29:09.359
<v SPEAKER_02>At least like with the prison populations, they needed to have consent.

00:29:09.599 --> 00:29:12.480
<v SPEAKER_02>They were given things in return, a time off.

00:29:12.640 --> 00:29:19.839
<v SPEAKER_00>So well, and those guys, like at the Atlanta State Penitentiary and at Stateville Prison, and at Sing Sing, like they lined up.

00:29:20.079 --> 00:29:32.960
<v SPEAKER_00>Our scientists would call them all into the into the yard and announce if you come and let us give you malaria and test some drugs on you, it's going to be really uncomfortable, but you're not going to die.

00:29:33.119 --> 00:29:38.480
<v SPEAKER_00>And we're going to give you free medical care on any other problems that you have, and maybe you'll get some time off.

00:29:38.720 --> 00:29:46.160
<v SPEAKER_00>They went to state hospital patients, then to prisons, and then if something was promising, then they would try it on troops overseas.

00:29:46.640 --> 00:29:59.200
<v SPEAKER_02>Um you know, you think of spying in wars, or at least I think of it as people are trying to find out the battle plans of their enemies and, you know, be able to then surprise attack or something like that.

00:29:59.440 --> 00:30:07.200
<v SPEAKER_02>But it seemed as though a lot of spying was going on as to the chemicals that were being used in the war.

00:30:07.359 --> 00:30:08.240
<v SPEAKER_02>Can you tell me about that?

00:30:08.480 --> 00:30:08.640
<v SPEAKER_00>Yeah.

00:30:08.720 --> 00:30:12.559
<v SPEAKER_00>So everything that the malaria project worked on was in blackout.

00:30:12.640 --> 00:30:14.720
<v SPEAKER_00>They couldn't, so you you you know scientists.

00:30:14.880 --> 00:30:16.319
<v SPEAKER_00>Scientists like to publish.

00:30:16.559 --> 00:30:20.160
<v SPEAKER_00>They discover something, they're like, I gotta get this down, I gotta get to get a new journal.

00:30:20.319 --> 00:30:21.440
<v SPEAKER_00>Somebody's gotta know about this.

00:30:21.599 --> 00:30:23.039
<v SPEAKER_00>This might feed their knowledge.

00:30:23.279 --> 00:30:26.160
<v SPEAKER_00>And all of these scientists are told this is a complete blackout.

00:30:26.319 --> 00:30:34.000
<v SPEAKER_00>You cannot talk about anything that you're doing because having a better malaria drug is a battlefield advantage.

00:30:34.160 --> 00:30:37.279
<v SPEAKER_00>Actually, probably as big a battlefield advantage as any.

00:30:37.440 --> 00:30:41.839
<v SPEAKER_00>Um, when we took Tunis, there was a researcher there named Gene Schneider.

00:30:42.000 --> 00:30:55.039
<v SPEAKER_00>He was French, but he had come down from France with instructions to use this secret compound, top secret compound, on these whitewashed adobe villages in Tunisia.

00:30:55.440 --> 00:30:59.920
<v SPEAKER_00>And he was in the middle of doing that when the Allies invaded North Africa.

00:31:00.720 --> 00:31:05.039
<v SPEAKER_00>He bundled up all that data and just waited to see which side was going to win.

00:31:05.279 --> 00:31:18.880
<v SPEAKER_00>And the Americans take Tunis and he asks for a very specific public health expert who he knew, and he he would he said, Here are my data sheets, here are my extra pills, and so that it was flown to the malaria project.

00:31:19.039 --> 00:31:21.119
<v SPEAKER_00>And we brought it back into our labs.

00:31:21.279 --> 00:31:27.200
<v SPEAKER_00>We turned some of the molecules around called a chloroquine, and they have their miracle drug.

00:31:27.519 --> 00:31:29.920
<v SPEAKER_00>That is wild, totally wild.

00:31:30.160 --> 00:31:37.279
<v SPEAKER_02>You know, there was this big push to find alternatives for quinine, to figure out how to mass-produce penicillin.

00:31:37.519 --> 00:31:43.839
<v SPEAKER_02>You know, they were kickstarted by the war, but they didn't end up really helping a ton until either the very end of the war or after the war.

00:31:44.160 --> 00:31:50.400
<v SPEAKER_02>Pfizer figured out how to make mass-produced penicillin in these like huge vats where they would grow up the mold.

00:31:50.559 --> 00:31:57.200
<v SPEAKER_02>And then at the very end of the war, in 1944, there was Woodward and uh I think it's pronounced Daring.

00:31:57.440 --> 00:32:01.680
<v SPEAKER_02>They figured out how to do the total synthesis of quinine.

00:32:01.920 --> 00:32:06.240
<v SPEAKER_02>So how to essentially make it from other materials you wouldn't need to get the bark.

00:32:06.559 --> 00:32:15.680
<v SPEAKER_02>What were like some of the other things that came out of the war that didn't really help then, but made a really big mark in chemistry later?

00:32:16.160 --> 00:32:17.759
<v SPEAKER_00>So you come out of World War II.

00:32:17.839 --> 00:32:20.960
<v SPEAKER_00>And chloroquine is the best drug to come out of the project.

00:32:21.119 --> 00:32:30.240
<v SPEAKER_00>We know that there were 14,000 drugs that were made and cataloged, and all of these compounds were then the property of the public.

00:32:30.400 --> 00:32:32.559
<v SPEAKER_00>And so all these other compounds were just shelved.

00:32:32.640 --> 00:32:34.480
<v SPEAKER_00>They were put in storage at NIH.

00:32:34.880 --> 00:32:44.240
<v SPEAKER_00>And when parasites developed resistance to chloroquine, researchers just went back to those shelves and they took those compounds off the shelves and they started testing them.

00:32:44.559 --> 00:32:54.640
<v SPEAKER_00>And most of the drugs used today for malaria still come from that catalog of drugs, with the exception of a Chinese herb-based drug called artemisinin.

00:32:54.799 --> 00:32:59.279
<v SPEAKER_00>That's a separate, really effective drug that did not come out of this World War II project.

00:33:00.319 --> 00:33:04.400
<v SPEAKER_02>What are some of the lasting effects of World War II?

00:33:04.559 --> 00:33:08.079
<v SPEAKER_02>And especially in the field of chemistry and pharma?

00:33:08.480 --> 00:33:13.119
<v SPEAKER_00>We didn't have a whole lot of drugs, really effective, good drugs coming out of the United States.

00:33:13.200 --> 00:33:14.960
<v SPEAKER_00>They were mostly coming out of Germany.

00:33:15.279 --> 00:33:25.759
<v SPEAKER_00>And the need for those pharmaceutical companies to really ramp up for the war and to get funding from the federal government to do the work, help them grow in size.

00:33:25.920 --> 00:33:31.599
<v SPEAKER_00>And then once they were large and competent and productive, they just kept going.

00:33:32.000 --> 00:33:38.880
<v SPEAKER_00>I think when people think of chemistry or they think of chemical companies or they think of pharmaceutical companies, they think of greed.

00:33:39.039 --> 00:33:46.160
<v SPEAKER_00>But when you when you look at examples like the Malaria Project, you do see how chemistry improves the lives of people.

00:33:46.400 --> 00:33:48.000
<v SPEAKER_00>What would we be without chemistry?

00:33:48.400 --> 00:33:55.759
<v SPEAKER_00>Because otherwise they wouldn't have they wouldn't have had anything to work with if our know-how in chemistry hadn't grown to meet the challenge.

00:34:00.000 --> 00:34:08.239
<v SPEAKER_01>Margot, I think it's hard to not be struck by the paradox between chemists working on both weapons and medicines.

00:34:08.639 --> 00:34:17.360
<v SPEAKER_01>I mean, you could argue that chemical warfare of World War I was cruel, and that the chemistry behind finding a cure for malaria was noble.

00:34:17.599 --> 00:34:20.480
<v SPEAKER_01>But of course, they were both in service of winning a war.

00:34:20.800 --> 00:34:21.119
<v SPEAKER_02>Right.

00:34:21.360 --> 00:34:26.320
<v SPEAKER_02>And they both had unintended consequences that countered their wartime goals.

00:34:26.559 --> 00:34:38.320
<v SPEAKER_02>So the blister agent, nitrogen mustard, derived from mustard gas, was found to shrink lymphomas, and so it was incorporated into multi-drug chemotherapy for Hodgkin's disease.

00:34:38.559 --> 00:34:44.159
<v SPEAKER_02>On the other hand, developing anti-malarials harmed to countless institutionalized people.

00:34:44.480 --> 00:34:56.000
<v SPEAKER_01>What's hard to deny are the consequences of so much investment into industrial and pharmaceutical chemistry, and how much that investment accelerated progress in chemistry.

00:34:56.320 --> 00:34:56.880
<v SPEAKER_02>Yes.

00:34:57.119 --> 00:35:04.400
<v SPEAKER_02>And how an expanding field would start to allow more scientific minds from different backgrounds to take part.

00:35:04.639 --> 00:35:06.559
<v SPEAKER_02>And that's on our next episode.

00:35:06.719 --> 00:35:08.559
<v SPEAKER_02>We'll see you next week.

00:35:11.440 --> 00:35:16.159
<v SPEAKER_02>This was Chain Reaction, a podcast by the American Chemical Society.

00:35:16.400 --> 00:35:18.960
<v SPEAKER_02>Our executive producer is Sam Jones.

00:35:19.119 --> 00:35:21.440
<v SPEAKER_02>The producer is me, Margot Wall.

00:35:21.679 --> 00:35:24.400
<v SPEAKER_02>Scripting and research was done by Beck Roldon.

00:35:24.719 --> 00:35:26.400
<v SPEAKER_02>Fact-checking by Michelle Boucher.

00:35:26.719 --> 00:35:29.679
<v SPEAKER_02>Production help from Michael David and Matt Radcliffe.

00:35:29.920 --> 00:35:31.119
<v SPEAKER_02>Theme song was by D.

00:35:31.280 --> 00:35:34.719
<v SPEAKER_02>Peter Schmidt with additional music by Blue Dot Sessions.

00:35:34.880 --> 00:35:39.920
<v SPEAKER_02>To learn more about our guests and their work, you can check out our show notes.