Cautionary Tales with Tim Harford - The Human Guinea Pigs of Camp Lazear

Episode Date: August 16, 2024

Young doctor Jesse Lazear has deadly Yellow Fever. He thrashes around and convulses in his sick bed, and his vomit is black. He is just 34 when he dies. Curiously, mosquito expert Lazear was researching the disease when he became ill. Some historians think his infection wasn't an accident, and that he was secretly experimenting on himself... Today, human challenge trials - where volunteers are intentionally given a disease under the watchful eye of medical support - are rare. The authorities are wary of the risks involved. But such trials can also mean that vaccines are developed faster and thousands of lives are saved. Is it time to start thinking differently about experimenting on humans? For a full list of sources, see the show notes at timharford.com.See omnystudio.com/listener for privacy information.

Pushkin a story of disaster, a story of enormous egos and enormous mustaches, a fraud and financial ruin, of hubris and despair. It's a story of new technologies and of death on a massive scale, and ultimately a story of understated genius. What's this story all about? A war? A revolution? No. Something even bigger. A canal. After you've finished listening to this cautionary tale, you might like to check it out. And now on with our episode and a quest to understand how the gruesome disease of yellow fever spreads.

of yellow fever spreads. John Moran enters building number two. It's a simple timber hut with just one room measuring 14 feet by 20. Dividing the room in two is a fine, strong wire mesh with holes of a fiftieth of an inch. Moran is wearing a night shirt, nothing else. He lies down on the bed. Around him buzz mosquitoes, fifteen mosquitoes, to be precise. Soon, one lands on his hand. He doesn't try to squish it or flick it off. The mosquito slides its proboscis through John Moran's skin

and sucks his blood. On the other side of the wirenet from Moran and the mosquitoes sits Major Walter Reed. He could tell you the life story of every one of those mosquitoes. They've been sucking the blood of people who are sick with yellow fever. We're in Cuba, in an improvised US army camp just outside Havana. It's the 21st of December, 1900. Four days later, on Christmas morning, John Moran wakes up with chills and a headache. He tries to eat his Christmas lunch, but he has no appetite. By the afternoon, his temperatures

climbed to 103. Is it yellow fever? Moran was 24 years old. He'd come to Cuba with the US Army, but left to get a civilian job as a clerk. It pays better, and Moran is trying to save money to take a degree in medicine. A few weeks earlier, when Major Reed had let it be known that he was looking for volunteers for his mosquito experiments, Moran's old army friends had made sure he knew about it. Reed will pay you, they told him, for several months' worth of salary. John Moran knew very well how deadly yellow fever can be. It had just killed the clerk

who worked next to him. He thought about it. Then went to introduce himself to Major Reed. I want to volunteer, said Moran. And I don't want money. I want to do it for science, for humanity. Major Reed looked at John Moran. I take my hat off to you," he said. John Moran was bravely taking a risk for noble motives. Are we too scared to let people take risks like that today? I'm Tim Harford, and you're listening to Cautionary Tales. What's it like to have yellow fever? Here's one victim, describing the onset of their symptoms.

It seemed as if every bone in my body had been crushed. My spine felt twisted and my head swollen and my eyes felt as if they would pop out of my head. Even the ends of my fingers felt as though they would snap off. If that's as bad as it gets, you're one of the lucky ones. In a week or two, you'll be okay again. But about 15% of people aren't lucky. Their illness develops a second, much more serious phase. Your skin turns yellow from jaundice. You're delirious from fever.

You start to bleed, perhaps from your eyes or your gums. Or perhaps inside your stomach. So when you vomit, your vomit's black. Organs start to fail. There's no treatment. If this second phase takes hold, your chance of surviving is little more than 50-50. No wonder Yellow Fever once caused such terror in America's port cities. Outbreaks didn't always spread far, but when they did, they were devastating. In 1793, yellow fever decimated Philadelphia, killing 5,000 people, one-tenth of the population.

In 1853, it did the same in New Orleans. Where it came from was clear enough. Ships from the Caribbean in the summer. But once it had arrived, how did it spread? Was it person-to-person contact? In Philadelphia, people stopped shaking hands. Many shrank with a fright at even the offer of a hand, observed one writer at the time. Acquaintances and friends avoided each other in the streets and only signified their regard by a cold nod. Or did yellow fever spread through something

in the air? In New Orleans, the authorities burned barrels of tar and whisky to try to clear the toxins. Or did it spread through contaminated objects? During the Civil War, a Confederate doctor plotted an early attempt at bioterrorism. He gathered clothes from people who died of yellow fever and tried to ship them to cities in the north. He even sent a suitcase full to Abraham Lincoln. The assassination attempt failed.

The doctor was later elected Governor of Kentucky. By 1900, the question of how yellow fever spread had become urgent for the US Army. The US had occupied Cuba, a hotbed of yellow fever. They had to figure out what to do to keep the troops as safe as possible. They set up a commission. At its head, Major Walter Reed. He'd just investigated how typhoid spreads on army bases. He'd concluded, rightly, that preventing typhoid was all about sanitation. Build latrines, wash hands. But the army had been improving sanitation in Cuba and rates of yellow fever were staying

stubbornly high. What worked for typhoid didn't work for yellow fever. So what were they missing? There were theories and puzzles, like the curious case of the court-martialed soldier. He was kept in a cell, on a military base, closely guarded, so they knew for sure that he hadn't had contact with anyone else who had been ill. Yet still he caught it and died. It was as if the disease had somehow… flown in through the bars of the cell window. Strange. Major Reed chose colleagues to assist him, his old friend James Carroll, her brilliant young doctor Jesse Lazier. They'd go to Cuba and try to work it out.

There was one theory that could explain the case of the court-martialed soldier. For 20 years, a Cuban doctor had been tirelessly championing his idea that a certain species of mosquito spread yellow fever. It was plausible enough on the face of it. Another species of mosquito had just been discovered to transmit malaria. Why not yellow fever too? The problem was that the Cuban doctor had been trying for 20 years to prove his theory with no success. He bred mosquitoes and let them feed on yellow fever patients. Then he persuaded nearly a hundred people to be bitten by those mosquitoes. If that seems like an insane thing to agree to, remember that it can't have seemed that much of a risk. Yellow fever was common, so

were mosquitoes, and hardly anyone bought the idea that the two were linked. And with every new volunteer, the doctor's theory seemed less and less likely to be true. Only a few of those bitten got ill, and most of them had symptoms that were hard to diagnose with confidence. They might have had a mild case of yellow fever, or it might have been something else. It was hard to say. Just one volunteer unmistakably got yellow fever soon after the mosquito bite, and who could be sure that wasn't a coincidence? He might have got it somewhere else. So the evidence wasn't promising. But Major Reed and his colleagues wanted to test the theory for themselves.

They visited the Cuban doctor, who gave them some mosquito eggs hid bread. The eggs were a jet black colour, one end rounded and blunt, while the other is slightly pointed, the whole closely resembling a Conchita cigar. Put them in water, said the Cuban doctor, and in 10 to 12 days you'll have mosquitoes. Reed put his young colleague Jesse Lazier in charge. That made sense. Lazier had worked on malaria. He knew mosquitoes. Lazier hatched the eggs and kept each mosquito in its own test tube, plugged with cotton. He'd take them to a hospital with a yellow fever ward, sit by the bedside of a patient, remove the cotton plug and put the open end of the test tube to the patient's skin.

He'd flick the test tube to get the mosquito moving. Once the mosquito had drunk its fill of the patient's blood, he'd plug the test tube to get the mosquito moving. Once the mosquito had drunk its fill of the patient's blood, he'd plugged the test tube again. Could these mosquitoes now infect someone with yellow fever? There was only one way to find out. Lazear put a test tube on his arm and let the mosquito feed on him. An army doctor said he'd take a bite too. How risky was it really? The Cuban doctor had done this to nearly 100 people

and almost all had been fine. The odds seemed firmly in their favour. Days passed and Lazier and the army doctor remained in perfect health. Other soldiers volunteered too. Nobody got ill. Lazier was fast giving up on the theory, he told his colleague on the commission, James Carroll. And now, one of his carefully nurtured mosquitoes seemed about to die. It had sucked the blood of one yellow fever patient, but had since been refusing to feed again. It was listless. Without another blood meal, it wouldn't last for long.

Carroll had never believed in the mosquito theory. Put your mosquito on me, he said. I'll see if I can feed it to keep it going for you. There were two things Jessie Lazier and James Carroll didn't know. They didn't know that for a mosquito to pass on yellow fever, it needs to have fed on someone in the first three days of their infection. Lazier had often fed his mosquitoes on patients who'd been sick for longer than that. Then, it takes at least 12 days for the mosquito to incubate the virus so it can pass it on when it bites someone else. Lazier generally hadn't been waiting that long before he put his mosquitoes onto healthy

volunteers. Lazier passed James Carroll the test tube with the ailing mosquito. As it happened, precisely 12 days had passed since this mosquito had fed on a yellow fever patient, according to Lazear's notes, a patient who'd been on day two of his illness. Carol rolled up his sleeve. Lazear put the test tube to Carol's arm. The mosquito didn't move. Lazear tapped the test tube to rouse it. Still nothing.

Lazear shrugged and began to take the test tube away. Give it here, said Carol. He held the test tube to his arm and waited patiently until at last the sluggish mosquito fluttered onto his arm and slipped its proboscis through his skin. Tales will be back in a moment. Three days after Jesse Lazier's ailing mosquito had fed on James Carroll's blood, the mosquito was doing well. So was James Carroll. He was enjoying a swim in the warm sea off a Cuban beach when he felt a sudden chill and a crushing headache. By the next day, Carol had been taken to hospital. He was running a fever of 105 and trying to say something about a mosquito.

The nurse couldn't follow it. He must be delirious. Jesse Lazear must have felt mortified. He'd failed time and again to produce a case of yellow fever. Had he finally succeeded when he wasn't even trying? Lazear sought out James Carroll's notebook. He wanted to see what Carroll had been doing for the last few days. If Carroll hadn't left the camp, which was fever-free, that would point convincingly to the mosquito as the

cause of the infection. But Carroll's notebook said he'd been visiting hospital wards and autopsy rooms where yellow fever victims were dissected. Skeptics would say that he could have got it anywhere. Still, at least Lazere now had a lead – A mosquito in a test tube that might have given yellow fever to James Carroll. Could that mosquito give it to someone else? Lazere needed another volunteer, but he soon found one. In the army camp, a young soldier expressed curiosity about his work. You still fooling with mosquitoes, Doctor?

Yes, said Lazier. Then, will you take a bite? Sure, replied the soldier. I ain't scared of them. The soldier said he hadn't been off the camp in two months. That was perfect. Lazier brought the test tube with the mosquito that had bitten James Carroll and put it to the soldier's arm. Five days later, the soldier began to feel unwell. It's hard to predict how badly you'll

get yellow fever. We now know there are different strains, some deadlier than others. But the younger you are, the better your chances. Children would often get it mildly and then be immune for life. The soldier was young and lucky. His case was mild. James Carroll was older and he was having a rougher time. Still in his hospital bed, writhing in pain and burning up, nurses giving him ice-cold enemas to try to bring his fever down. Jesse Lazier was desperately worried about James Carroll, but he was excited too. I rather think I am on the track of the real germ," he wrote back home. But nothing must be said as yet. Not even a hint. And then the story gets murky.

The Yellow Fever Commission, remember, was headed by Major Walter Reed. Where was Major Reed while all this drama was unfolding in Cuba? Reed was back in America. He had to finish his big report on typhoid and present it to his bosses in Washington DC. He got a telegram describing his old friend James Carroll's bite and illness. He wrote back, I cannot begin to describe my mental distress over this most unfortunate turn of affairs. The next piece of news was more positive. Carroll, at last, had begun to pull through. His fever was down. There'd been none of the dreaded black vomit. He was weak, but he'd live.

Reed fired off a letter. My dear Carol, hip, hip hurrah! God be praised. I can never recall such a sense of relief in all my life. I shall simply go out and get boiling drunk. God bless you, my boy. And then another telegram. Jesse Lazear had got yellow fever. The message was blunt. Severe case. What had happened? According to Jesse Lazear, this is what had happened. He was in a hospital, at the bedside of a yellow fever patient, holding a test tube to the patient's skin. The mosquito in the tube had just started to feed. Then, said Lazier, another mosquito that happened

to be in the room landed on his hand. He didn't want to move because he'd disturbed the insect in the test tube and have to start all over again. And he thought the mosquito on his hand was from a different species, one that wasn't suspected of spreading the disease. So he let the mosquito bite him. Historians think that isn't plausible. Lasear, remember, was a mosquito expert. He'd studied malaria. He'd been spending day after day intently observing his mosquitoes in test tubes. He affectionately called them his birds.

In their book, Yellow Jack, the authors John Pierce and James Reiter say, It simply does not make sense that Lazier did not recognise what species of mosquito had landed on his own hand. What historians think happened is this. Jesse Lazear experimented on himself. Again. The day he claimed he'd been bitten by accident, September 13th 1900, Lazear's notebook contains a cryptic entry. Up till then, he'd recorded the names of all his volunteers, along with the history

of the mosquitoes that fed on them. This entry simply said, Guinea pig number one. And the mosquito? It had fed on a patient in the second day of his illness, 14 days earlier. If Lazier had formed a theory about the timelines required to transmit yellow fever, this was exactly the mosquito he'd have chosen to put that theory to the test. It's possible, of course, that Lazere had suddenly decided to feed one of his mosquitoes

on an actual guinea pig. But as nobody on the commission had ever discussed doing experiments on guinea pigs, it seems unlikely. We can only presume that guinea pig number one was Jesse Lazier. Why test it on himself? And why hide it? We'll never know. Five days after guinea pig number one was bitten, Jesse Lazier began to feel unwell. He sat down to write a letter to his mother, who was taking care of his wife, back in America. His wife had just given birth to their second child. He didn't mention his illness. Dear little Houston must be very cute, he wrote. Houston was their toddler.

The next day, Lazir was carried to the hospital. James Carroll had recovered enough just about to shuffle over to Lazier's bedside. I shall never forget the expression of alarm in his eyes, he said. Lazier's illness moved quickly to the deadly second stage. He thrashed around so much, nurses had to call for soldiers to strap his wrists and ankles to the bed. He began to convulse and vomit. The vomit was black. Jesse Lazier was 34 years old when yellow fever killed him. As Major Walter Reed prepared to return to Cuba, he had a problem. It wasn't just that one of his team was dead and another would need a long time off to recover. Their self-sacrifice had gone to waste. They'd been brave in getting bitten, but they hadn't been scientific.

As Reed explained in a frustrated letter to the convalescing James Carroll. If you, my dear doctor, had prior to your bite remained at the camp for ten days, then we would have a clear case. But you didn't. You went just where you might have contracted the disease from another source. And what about Jesse Lazier? According to his own account, he had been bitten while at a yellow fever hospital, for goodness sake. That knocks his case out, wrote Reed.

I mean as a thoroughly scientific experiment. There was the young soldier Lazear had infected with the same mosquito as Carol. His case was highly suggestive, but not conclusive, not yet. To remove any doubt, Walter Reed was going to have to do more thoroughly scientific experiments. And for that, he'd need more volunteers. Cautionary Tales will return. Walter Reed needed a site to construct a new camp. It had to be in a part of Cuba that wasn't known for yellow fever. He needed well-drained land, with no stagnant water for mosquitoes to breed.

He couldn't risk stray mosquitoes buzzing in to mess up his experiments. He found a two-acre site and brought in brand new tents and equipment, so nobody could say they might have been contaminated. He had the workers quarantined to make sure they weren't harbouring the disease. He then had them tested for fever three times a day. The workers put up the tents and two simple wooden buildings. In honour of their fallen colleague, they called it Camp Lusir. Building number one had nothing to do with mosquitoes. Reed wanted to disprove once and for all the idea that contaminated clothing could spread yellow fever. It was a simple

wooden shack, 14 feet by 20, with shuttered windows. By now it was November, the weather was cooling down. Reed wanted a fair test in tropical conditions, so he had a stove installed in the room, to keep the temperature above 90 degrees Fahrenheit. Reed got three volunteers to go into the dark and sweltering hut with a tightly sealed trunk he'd had sent from the Yellow Fever ward at a nearby hospital. The trunk contained bedsheets and blankets, all soiled with a liberal quantity of black vomit, urine and fecal matter. The three men cracked open the trunk and straight away ran back outside gasping and retching. They got their breath, steeled their nerves and went back in.

They took the fetid sheets and blankets out of the trunk and gave them all a good shake. If there were contagious particles that ought to spread them around. Then they put the sheets on the beds in the hut and slept on them for 20 nights. We all felt like we were coming down with yellow fever every day, said one. But they didn't. It was conclusive proof that this long-held theory was wrong. The Kentucky doctor's suitcase could never have killed Abraham Lincoln. Walter Reed had been confident that the volunteers in building number one were never in danger

of death, just discomfort. The mosquito experiments were a different matter. Reed had studied Jessie Lazier's notebook. He'd talked to the young soldier Lazier had infected and had drawn the correct conclusion. He needed an incubation period of at least 12 days. The new knowledge meant Reed's experiments at Camp Lazear wouldn't be like Jessie Lazear's earlier, more casual attempts, when the volunteers could take comfort in odds of one in a hundred. Reed knew that his volunteers were very likely to get yellow fever. He wanted them to know that. So Reid had a form typed up, spelling out the risks, and every time someone asked to volunteer, he got them to sign it.

Informed consent is standard practice now. Reid was its pioneer. But why would anyone sign? We heard already the young idealist John Moran explain his reasons for science and humanity, and Moran didn't want the money, even though he was saving hard to go to medical school. And in today's terms, Reid was offering many thousands of dollars. Others did want the money. And they had another pragmatic reason too. If you moved to Cuba from a place without yellow fever, so you weren't immune from childhood, you felt sure you'd get it sooner or later. So why not take your chances now, knowing you'd have the most attentive medical care the US Army could offer?

In March 2020, the enormity of the Covid pandemic was starting to dawn on the world. Most of us were trying to make sense of the present, but three academics were looking to the future. We're going to need vaccines, they said, as quickly as possible. Those vaccines were already being developed and would need to be tested. But the traditional clinical trial might take a long time. A big group of volunteers would receive either the new vaccines or a placebo, and would then go about their daily lives. Some of them, eventually, would get COVID, allowing scientists to figure out whether most of these cases were in the placebo group, in which case the

vaccine would have worked. But since most people around the world were trying very hard not to spread the virus, just waiting for enough of those infections to happen by accident could take months. Wouldn't it be quicker to deliberately expose your volunteers to COVID? That's called a human challenge trial, and they've often been used to develop other vaccines. Josh Morrison ran a health non-profit in New York. He thought, I'd volunteer to get COVID if it might speed up a vaccine that could get

life back to normal. Would other people too? He set up a website called One Day Sooner and word spread. Within weeks, tens of thousands of people signed up to say they'd do it if someone asked them. Some expressed motives much like John Moran's. They'd do it for science, for humanity. Others were pragmatic, like other yellow fever volunteers. They said they thought they'd get COVID anyway

and they liked the idea of getting it when doctors and nurses would be watching them closely. But many decision makers were wary about the idea of challenge trials for COVID. They're usually used for diseases we have a good idea of how to treat. At the time, we couldn't treat Covid. So what? said Josh Morrison. This is a global emergency. We can't take the risk, said others. What if someone dies? The debate rumbled on through the summer of 2020.

Challenge trials didn't happen for the first set of vaccines. They were tested in the usual way. One day sooner became an advocacy group for challenge trial volunteers. Later they funded researchers to ask how many lives might have been saved if the first vaccines had come, say, 30 days earlier? 63,000, the researchers estimated, in the US and UK alone. It's hard to be sure if challenge trials really would have given us vaccines 30 days earlier. But this isn't really about COVID. It's about looking ahead to the next pandemic and what we might learn.

One possible lesson, let's be more proactive about lining up challenge trials. Let's be more hard-headed about the trade-offs. When we ask, what if we have a trial and someone dies? Let's also ask, what if we don't have a trial and 63,000 people die? We can't eliminate risk, but we can take calculated risks in a way that advances our knowledge. If we have another global emergency and selfless volunteers again raise their hands, let's not allow their bravery to go to waste.

Jesse Lazier and James Carroll wasted their bravery, because they gave themselves yellow fever in a way that scientifically proved nothing. Walter Reed was determined not to waste the courage of his new volunteers, such as John Moran. He needed to conduct experiments that nobody would be able to nitpick. In Building Number 2, Reed wanted to put to rest the idea that led New Orleans authorities to burn barrels of whisky and tar. The theory that yellow fever spreads through toxins in the air. A fine, strong wire mesh ran down the middle of the room. On one side, 15 mosquitoes and John Moran.

On the other side, not only Reed, but two more volunteers acting as controls. They slept in their half of the hut, breathing the same air as John Moran. On Christmas Day, John Moran got yellow fever. The other two never did. Moran was young and lucky. His case was mild, and he recovered. was young and lucky. His case was mild and he recovered. By early February 1901, Walter Reed was ready to report the results of his thoroughly scientific experiments in a speech to a medical congress in Havana. He explained how it proved that

yellow fever didn't spread through dirty objects. It didn't spread through the air. It spread through mosquitoes. The hall was packed, wrote Reed to his wife. The applause, long and hardy. The authorities in Havana set up mosquito brigades to try to rid the city of the mosquitoes that spread yellow fever. They went from house to house. Most had no piped water. Instead, people collected rainwater in open barrels. Mosquitoes laid their eggs on the surface of that water. The mosquito

brigades poured oil on top. Just a thin film was enough to suffocate the larvae. As the mosquitoes disappeared, so did the disease. Over the previous 10 years, Havana had averaged 462 yellow fever deaths a year. In the rest of 1901, there were five. James Carroll never fully recovered from his fight with yellow fever. His heart failed a few years later. Walter Reed died early too, though not from yellow fever, a ruptured appendix. His name lives on in the Walter Reed National Military Medical Centre in Bethesda, Maryland. But I was curious. What happened to John Moran,

the poster boy for selflessness, with the dream of being a doctor? I found an obituary from 1950. Moran had lived to 74. He'd settled in Cuba and built a distinguished career as… an oil man. What happened to saving for medical school? Soon after his bout of yellow fever, the obituary said, Moran took the money he'd saved so far and invested it in a get-rich-quick oil scheme. The scheme failed. Moran had to give up on his ambition to study. He got a job in the oil industry instead and worked his way up. I can't help wondering if he'd have felt that need to gamble his savings if only he'd taken the payment from Walter Reed. He'd surely earned it. John Moran risked his life for an experiment. Then risked his savings for his dream career.

One risk paid off, one didn't. That's the nature of risks. When Jesse Lazier and James Carroll took the risk of being bitten by a mosquito, we learned far too little because a proper scientific experiment wasn't in place. And when the volunteers of One Day Sooner were willing to take a similar risk in the face of Covid, we learned far too little yet again. Because a proper scientific experiment just seemed too bold for policymakers to approve. But there'll always be people who'll take risks as a gift to help others. Shouldn't we be prepared to accept that gift? Fever, as is Yellow Jack by John Pierce and James Reiter.

For a full list of our sources, see the show notes at timharford.com. If you enjoyed this tale, I recommend you hop on over to Pushkin Plus and check out my brand new pair of episodes on the Panama Canal. Yellow Fever wreaks havoc on this mega project, just one of many obstacles faced by the French and the Americans on their mission to dig a waterway across Central America. Co-Optionary Tales is written by me, Tim Harford, with Andrew Wright. It's produced by Alice Fiennes with support from Marilyn Rust. The sound design and original music is the work of Pascal Wise. Sarah Nix edited the scripts. It features the voice talents of Ben Crowe,

Melanie Guthridge, Stella Harford, Gemma Saunders and Rufus Wright. The show also wouldn't have been possible without the work of Jacob Weisberg, Ryan Dilley, Greta Cohn, Eric Sandler, Carrie Brody and Christina Sullivan. Cautionary Tales is a production of Pushkin Industries. It's recorded at Wardour Studios in London by Tom Berry. If you like the show, please remember to share, rate and review. Tell your friends. And if you want to hear the show ad free, sign up for Pushkin Plus on the show page in Apple Podcasts or at pushkin.fm slash plus.