Futility Closet - 201-The Gardner Heist
Episode Date: May 21, 2018In 1990, two thieves dressed as policemen walked into Boston's Gardner museum and walked out with 13 artworks worth half a billion dollars. After 28 years the lost masterpieces have never been recove...red. In this week's episode of the Futility Closet podcast we'll describe the largest art theft in history and the ongoing search for its solution. We'll also discover the benefits of mustard gas and puzzle over a surprisingly effective fighter pilot. Intro: In 1938, Italian physicist Ettore Majorana vanished without a trace. Many of the foremost intellectuals of the early 20th century frequented the same café in Vienna. Sources for our feature on the Gardner heist: Ulrich Boser, The Gardner Heist: The True Story of the World's Largest Unsolved Art Theft, 2008. Stephen Kurkjian, Master Thieves: The Boston Gangsters Who Pulled Off the World's Greatest Art Heist, 2015. Michael Brenson, "Robbers Seem to Know Just What They Want," New York Times, March 19, 1990. Peter S. Canellos, Andy Dabilis, and Kevin Cullen, "Art Stolen From Gardner Museum Was Uninsured, Cost of Theft Coverage Described as Prohibitive," Boston Globe, March 20, 1990, 1. Robert Hughes, "A Boston Theft Reflects the Art World's Turmoil," Time 135:14 (April 2, 1990), 54. Peter Plagens, Mark Starr, and Kate Robins, "To Catch an Art Thief," Newsweek 115:14 (April 2, 1990), 52. Scott Baldauf, "Museum Asks: Does It Take a Thief to Catch a Degas?," Christian Science Monitor 89:193 (Aug. 29, 1997), 3. Steve Lopez and Charlotte Faltermayer, "The Great Art Caper," Time 150:21 (Nov. 17, 1997), 74. "Missing Masterpieces," Security 37:6 (June 2000), 14-18. Robert M. Poole, "Ripped From the Walls (And the Headlines)," Smithsonian 36:4 (July 2005), 92-103. Paige Williams, "The Art of the Story," Boston Magazine, March 2010. Randy Kennedy, "20th Anniversary of a Boston Art Heist," New York Times, March 17, 2010. Mark Durney and Blythe Proulx, "Art Crime: A Brief Introduction," Crime, Law and Social Change 56:115 (September 2011). Katharine Q. Seelye and Tom Mashberg, "A New Effort in Boston to Catch 1990 Art Thieves," New York Times, March 18, 2013. Tom Mashberg, "Isabella Stewart Gardner: 25 Years of Theories," New York Times, Feb. 26, 2015. Shelley Murphy, "Search for Artworks From Gardner Heist Continues 25 Years Later," Boston Globe, March 17, 2015. Tom Mashberg, "Arrest by F.B.I. Is Tied to $500 Million Art Theft From Boston Museum, Lawyer Says," New York Times, April 17, 2015. Serge F. Kovaleski and Tom Mashberg, "Reputed Mobster May Be Last Link to Gardner Museum Art Heist," New York Times, April 24, 2015. "New Video in 25-Year-Old Art Heist at Boston's Isabella Gardner Museum," New York Daily News, Aug. 6, 2015. Tom Mashberg, "25 Years After Gardner Museum Heist, Video Raises Questions," New York Times, Aug. 6, 2015. Rodrigue Ngowi and William J. Kole, "2 Suspects in Boston Art Theft Worth $500 Million Are Dead, FBI Says," Washington Post, Aug. 7, 2015. Sarah Kaplan, "Surveillance Video Raises Questions — and Possible Clues — in 25-Year-Old Museum Mystery," Washington Post, Aug. 7, 2015. Justin Peters, "Why Is Stolen Art So Hard to Find?," Slate, Aug. 14, 2015. Erick Trickey, "The Gardner Museum Heist: Who's Got the Art?," Boston Magazine, March 13, 2016. Shelley Murphy and Stephen Kurkjian, "Six Theories Behind The Stolen Gardner Museum Paintings," Boston Globe, March 18, 2017. Graham Bowley, "Gardner Museum Doubles Reward for Recovery of Stolen Masterpieces," New York Times, May 23, 2017. Edmund H. Mahony, "Stubborn Stand-Off Over Stolen Gardner Museum Art Could End With Sentencing of Hartford Gangster," Hartford Courant, Sept. 5, 2017. Katharine Q. Seelye, "Clock Is Ticking on $10 Million Reward in Gardner Art Heist," New York Times, Dec. 26, 2017. Camila Domonoske, "Got the Scoop on the Gardner Museum Art Heist? You Have 4 Days to Earn $10 Million," The Two-Way, National Public Radio, Dec. 27, 2017. Edmund H. Mahony, "Museum Extends $10 Million Reward in Notorious Boston Gardner Museum Art Heist," Hartford Courant, Jan. 11, 2018. Colin Moynihan, "Gardner Museum Extends $10 Million Reward for Information in Art Heist," New York Times, Jan. 11, 2018. Nadja Sayej, "Will Boston's $500m Art Heist Ever Be Solved?," Guardian, Jan. 19, 2018. Leah Silverman, "Suspect in the Isabella Stewart Gardner Museum Heist Sentenced to Four Years in Prison," Town & Country, Feb. 28, 2018. Sarah Cascone, "Paintings Stolen in America's Biggest Art Heist Have Returned to Their Frames -- Thanks to Augmented Reality," Artnet, March 26, 2018. "Learn About the Theft," Isabella Stewart Gardner Museum (accessed April 29, 2018). Listener mail: Derek Lowe, "Understanding Antidepressants -- or Not," Science Translational Medicine, Feb. 12, 2018. Johnathan Frunzi, "From Weapon to Wonder Drug," Hospitalist, February 2007. "Evolution of Cancer Treatments: Chemotherapy," American Cancer Society (accessed May 17, 2018). Augustus De Morgan, A Budget of Paradoxes Reprinted, With the Author's Additions, From the Athenaeum, 1872. Robert and Michele Root-Bernstein, "Medicinal Notes: Honey Works Better Than Cow-Dung," Independent, May 4, 1999. Ole Peter Grell, Paracelsus, 1998. This week's lateral thinking puzzle was contributed by listener Steven Jones. You can listen using the player above, download this episode directly, or subscribe on Apple Podcasts or Google Play Music or via the RSS feed at http://feedpress.me/futilitycloset. Please consider becoming a patron of Futility Closet -- you can choose the amount you want to pledge, and we've set up some rewards to help thank you for your support. You can also make a one-time donation on the Support Us page of the Futility Closet website. Many thanks to Doug Ross for the music in this episode. If you have any questions or comments you can reach us at podcast@futilitycloset.com. Thanks for listening!
Transcript
Discussion (0)
Welcome to the Futility Closet podcast, forgotten stories from the pages of history.
Visit us online to sample more than 10,000 quirky curiosities from a vanishing physicist
to a momentous cafe.
This is episode 201.
I'm Greg Ross.
And I'm Sharon Ross. In 1990, two thieves dressed
as policemen walked into Boston's Gardner Museum and walked out with 13 artworks worth half a
billion dollars. After 28 years, the lost masterpieces have never been recovered. In
today's show, we'll describe the largest art theft in history and the ongoing search for its solution.
the largest art theft in history and the ongoing search for its solution.
We'll also discover the benefits of mustard gas
and puzzle over a surprisingly effective fighter pilot.
Just a reminder that this podcast
is supported primarily by our wonderful patrons.
And this week we're sending out a big thank you
to Jason Bucata, our newest super patron,
who has pledged a very generous $20 an episode. If you value this show and want to give some of
that value back, please check out our Patreon page at patreon.com slash futilitycloset. And
thanks so much to Jason and all of our incredible supporters. We really appreciate every donation and pledge.
In the early hours of March 18, 1990, just after the end of St. Patrick's Day, a group of celebrating students walked past the Isabella Stewart Gardner Museum in Boston, a striking
Venetian-style building in the city's Fenway-Kenmore neighborhood. They noticed something odd. Two men
dressed as city police officers were sitting in a small red hatchback on Palace Road.
The car was unmarked and it didn't have a police license plate.
The students thought this was strange, but they were high school seniors and didn't want to get into trouble for underage drinking, so they moved on.
A little after 1 a.m., the men got out of the car, went to the side entrance of the four-story building, and pressed a buzzer.
The security guard, a 23-year-old student named Richard Abath,
answered, and they said, police, let us in. We heard about a disturbance in the courtyard.
Abath let them in, and the cops asked whether there were any other guards in the building.
Abath said there was one, and they said, get him down here. Abath summoned the other guard,
and then one of the cops told him, you look familiar. I think we have a default warrant
out on you. Come out here and show us some identification. Abath came around the desk, which took him away from the panic button, the only
direct connection with the outside world. The cops handcuffed him and the other guard and told them,
this is a robbery. Don't give us any problems and you won't get hurt. They wrapped duct tape around
the guard's eyes and mouths and led them down to the basement and secured them at either end of a
long hallway. One of the thieves took their wallets and said, we know where you live. Do as I say and no harm will come to you. The thieves left the guards in
the basement and made their way into the museum, which contains tens of thousands of valuable
artworks. There were no other defenses, no video cameras, and no other guards. At 1.48 a.m., they
tripped a motion sensor in the Dutch room designed to go off when visitors got too close to an
exhibit. One of the thieves kicked the buzzer silent, and nothing happened. The museum's security system
wasn't connected to the local police precinct. In the Dutch room, the thieves took down Rembrandt's
only seascape, the Storm on the Sea of Galilee, smashed it out of its frame, and cut it off its
stretcher with a knife. They did the same with Rembrandt's Lady and Gentleman in Black. In the
same room, they picked up Vermeer's The Concert, one of only 36 surviving works by that artist. And they moved on through the museum,
picking up a bronze beaker from China's Shang era, five sketches by Degas, and Manet's Chez
Tortoni. When they had everything they wanted, they checked again on the security guards in
the basement. They asked them if they were comfortable and if their handcuffs were too
tight. Then they went back to the first floor, kicked open the security director's office,
ripped open the video recorders that had filmed their entrance, and took the cassettes.
Now there was no visual record of their faces.
They also grabbed the data printouts from the motion detectors,
which had recorded their movements within the building.
That data was also stored on the hard drive, but they don't seem to have known that.
And finally, apparently as a taunt,
they left the empty frame of a Manet painting on the security director's chair. At 2.41 a.m., they stepped out
the side door of the museum, probably to a van or truck. It took two trips to transfer all the loot.
The building's side door closed for the last time at 2.45 a.m. The two men had been inside for a
total of 81 minutes and stole 13 works of art, valued today at more than $500 million.
The museum calls it the single largest property theft in the world.
It's certainly the largest art theft in history.
The FBI assigned 30 agents to the case and got assistance from Scotland Yard, sympathetic museum directors and art dealers,
Japanese and French authorities, hundreds of detectives, and thousands of private citizens, but the theft remains unsolved. No one has ever been charged with the crime, and none of the stolen items
have been recovered. At a news conference, the museum's director, Anne Hawley, said the theft
had made her feel, quote, as if I have experienced the death of a dearest friend. She said, a part
of our heritage has been stolen from us. It was a barbaric act. The museum devoted more than $50,000
a year to investigating the theft and had
offered a reward for any information on the whereabouts of the stolen artworks. $1 million
at first, then $5 million, and finally $10 million, the biggest bounty ever offered by a private
institution. The lead FBI agent, Thomas Cassano, told the Boston Globe in 2000,
it's the biggest whodunit I've ever worked on as well as the most frustrating. Investigators got
plenty of leads, but there wasn't much physical evidence to go on.
The forensic team managed to pull about a dozen latent fingerprints from the picture frames,
but they were never sure whether those belonged to the thieves.
FBI agent Dan Fausen told the author Ulrich Boeser,
I have never heard of another case on the magnitude of the Gardner
where you didn't have a single concrete piece of evidence.
Really, even still to this day, I don't even know if the thieves wore gloves or not. In the 28 years since the theft,
there's been almost constant speculation as to who was behind the crime. At one point, the FBI even
resorted to using psychics with no results. The first possibility is that the paintings were
stolen on commission, that some evil connoisseur had hired the thieves to steal certain particular
paintings that he wanted for his own collection, and he's hung those in his lair where he sips cognac and cackles
maniacally. FBI agent Jeffrey Kelly said, it's difficult to understand why the thieves took what
they did, an eclectic collection. They were certainly in the museum long enough to take
whatever they wanted. They treated the guards well. That's professional. That may suggest that
the thieves had targeted certain paintings because they'd been told to. Unfortunately, theft on commission pretty much only happens in the
movies. In fact, this is sometimes called the Dr. No theory. Robert Holmes, a Boston-area lawyer
who specializes in art cases, told Newsweek, part of the satisfaction of owning a masterpiece is
telling the world you own it. It just doesn't happen that art connoisseurs steal masterpieces
so they can gloat over them in private. Another sign that the theft wasn't commissioned by an art lover is that the thieves
seemed pretty undiscriminating. The Vermeer they took is one of the most valuable stolen items in
the world, worth as much as $300 million. But they also stole the decorative finial from the end of
a flagpole, apparently because it looked like gold or they thought it might make a good souvenir.
And they stole it when they were standing less than 100 yards away from Titian's Rape of Europa, which Peter Sutton of Boston's
Museum of Fine Arts called arguably the greatest painting in America. And on their way to the
flagpole, they passed by two Raphaels and a Botticelli. So this doesn't seem to have been
a carefully planned theft. Anthony Amore, the Gardner Museum's Director of Security, says,
The idea of a professional art thief, a cat burglar who goes and steals masterpieces, is fiction. It has nothing to do with people who
want art for the collection. It's people stealing these things for money. That's bad because it
means the criminals are more likely low-level thieves who now find themselves stuck with art
that's too valuable to get rid of. Hardly anyone who steals a masterpiece does it again because
they discover that they can't fence it. The criminologist A.J.G. Tawis says obtaining the ransom without exposing oneself in practice
turns out to be far more difficult for criminals than the actual theft. Trying to sell a stolen
masterpiece is dangerous. Anyone knowledgeable enough to want to buy it would also know that
it had been stolen. If I stole the Mona Lisa and tried to sell it to you, you'd be crazy to take
it. You'd never find another buyer for it, and if you were caught with it, you couldn't plausibly claim that you didn't know it was stolen.
It's the Mona Lisa. Of course it's stolen.
Markets do exist for stolen masterpieces.
For example, they can be collateralized and used as currency in underworld deals for guns or drugs,
but penny anti-thieves don't know how to reach the black market.
Another possibility is that the Gardner heist was what's called an insurance theft.
That means the crooks were hoping to negotiate with the museum's insurance company, offering to return the
paintings for a fraction of their value. Insurance companies are usually willing to negotiate,
but in this case there was no insurance. The museum had insured its holdings against damage,
but not theft. That would have cost $3 million a year, and the Gardner's total operating budget
was only $2.8 million. But the thieves had no way
of knowing that. On the other hand, if the thieves had been hoping to ransom back the paintings,
then you'd think they'd have been more careful to steal the most valuable works, which they didn't
do. In any case, when thieves realize they can't easily sell a masterpiece, they often just put it
in storage or even destroy it. As a result, only about 10% of art thefts are ever solved.
As I mentioned, the Gardner has offered a reward for information leading to recovery of the paintings, but rewards tend to attract nuts
and people offering theories rather than hard leads. The art detective Harold Smith set up a
toll-free number and a website shortly after the Gardner theft to solicit help from the public,
and he received hundreds of useless tips over the years. The author Ulrich Boeser writes,
one woman said that she'd seen the ghost of Isabella Stewart Gardner and that the paintings were tucked into a hollow door in a house in Scotland.
A cleaning lady claimed that she had caught a glimpse of the artworks in a closet,
but she couldn't remember where.
Another caller said that her previous employer had put the paintings in the trunk of a car
that was buried under a mountain of dirt, and only she knew where it was.
If the reward doesn't produce any leads, we're stuck trying to solve the case by investigation.
One theory is that the museum's security guard, Richard Abath, was in on the theft.
Museum guards aren't paid much, and the FBI estimates that as many as 80% of museum
robberies are inside jobs. Abath buzzed in the thieves. He said he was unaware of a rule that
forbid letting unauthorized people into the building. That's a huge oversight. At the nearby
Museum of Fine Arts,
curator Cornelius Vermeule told Newsweek, if a group of nuns say their van broke down and want to call the Mother Superior, we don't let them in. They might turn out to have Uzis under their
habits. Also intriguingly, motion sensors show that on the night of the robbery, the thieves
never entered the first floor gallery where Manet's Chez Tortoni was stolen. Only Abath Steps
went there during
his rounds before the thieves arrived. Also, he briefly opened the side door before the thieves
arrived, and video released just three years ago shows that Abath allowed an unauthorized visitor
into the museum on the night before it was robbed in what might have been a dry run. It's not clear
whether Abath is still under scrutiny. He's cooperated fully so far, and he doesn't seem
to have benefited by the crime. There's a long list of other possibilities. Many involve petty
thieves in Boston and mafia families in Connecticut and Pennsylvania. The FBI has said that the stolen
artworks were offered for sale in Philadelphia in the early 2000s and says it believes the heist
was organized by a criminal organization based in the Mid-Atlantic and New England area.
The leading theory surrounds Carmelo Merlino,
the owner of a Boston car repair shop,
and two associates, George Riesfelder and Leonard DiMuzio.
Riesfelder and DiMuzio resembled police sketches of the museum thieves,
and Riesfelder drove a red Dodge Daytona that was similar to the car the students had seen outside the museum.
Both men died in 1991,
which points at the urgency of the investigation.
The theft happened 28 years ago now, and the generation involved in it is passing away.
One of the most promising remaining leads concerns Robert Gentile, a used car salesman in Manchester, Connecticut, who's reputed to be a member of organized crime.
Gentile denies any connection to the missing artworks, and he hasn't been charged in the theft, but in 2014, he boasted to an undercover FBI informant that he had access to two of the paintings, one a Rembrandt, and could arrange a sale for $500,000 or more. In February 2012,
federal agents searched a shed in Gentile's backyard and found a list of items taken from
the museum along with prices indicating their black market value, and prosecutors said Gentile
performed poorly on a lie detector test when questioned about the theft. Gentile was sentenced just this February on unrelated federal gun charges. He still denies any knowledge of the
paintings, but Assistant U.S. Attorney John H. Durham said in 2015, there is a 99% certainty
that Mr. Gentile was lying when he said he didn't know anything about the Gardner Museum robbery
before it happened. He'd never seen any of the Gardner paintings and didn't know where any of
them were. But if investigators don't get a confession soon, the trail may grow cold. Gentile, who's now 81, is thought to be the last living
person connected with the robbery. That doesn't mean all hope is lost. In 2013, FBI Special Agent
Jeffrey Kelly said that the stolen works have likely changed hands several times by now and
that the people who have them now might not realize their significance or that they were stolen.
It's not unusual for art thieves to hold stolen artworks for several years as they wait for investigators to lose hope,
for the paintings to increase in value, and for statutes of limitations to run their course.
Anthony Amore, the museum's director of security, says that in most art thefts, the stolen works
turn up either immediately or a generation later, after someone who knows about the theft develops
a reason to go to the authorities. A jilted lover, for example, or an estranged child. And some criminals keep stolen artworks
as bargaining chips in case of future trouble as a sort of get-out-of-jail-free card.
And, as I mentioned, sometimes they're used as collateral in drug or arms deals. If that's the
case, we may have no word of the paintings until a debt is paid off, which may be many years.
Today, if you visit the Gardner Museum, you'll see empty frames where
the stolen paintings once hung. But the museum, the FBI, and the U.S. Attorney's Office are still
hoping to recover them. Most stolen art that's recognizable is found close to home. There's no
point in moving it because it can't be fenced. Anthony Amore, the security director, believes
the stolen paintings are still within a 60-mile radius of Boston. The museum is still offering
a reward of $10 million for information
that leads directly to the recovery of all the items in good condition, and Amore says you don't
have to hand us the paintings to be eligible for the reward. If you have the stolen artwork,
you can't be charged with art theft. The statute of limitations has run out. You could still be
charged with possession of stolen property, but in 2013, U.S. Attorney Carmen Ortiz said there was a
very strong possibility that a person who returned the stolen items could receive immunity. In public statements, the museum has
said over and over that they just want their paintings back. Amore has even offered to deliver
the reward anonymously, perhaps through an attorney. That way, since he himself is not a law
enforcement agent, there would be no danger of arrest. If you have any information, you can write
to theft at gardnermuseum.org. They guarantee
confidentiality. Beyond the reward, the museum hopes that someone will return the paintings
because it's the right thing to do. Curator Alan Chong said, thousands of people are now
unable to experience these works of art. Something that might inspire people, that might transform
lives, is missing. Anne Hawley, the museum's director, said, think of what it would mean to
civilization if you could never hear Beethoven's Ninth Symphony again. Think if you lost access to a crucial piece of literature
like Plato's Republic. Removing these works by Rembrandt and Vermeer is ripping something from
the very fabric of civilization. And Anthony Amore, the director of security, told The Guardian just
this January, doing security at the museum is my job, but solving this case is my life.
The problem is not the volume, it's the quality of drug development and drug repositioning.
Lindsay Flint wrote, Dear Greg, Sharon, and Sasha, I just caught up on the most recent
episodes of the podcast and was really excited to hear you talking about the process of drug
discovery because I help design and run preclinical screening assays to find drugs to treat tuberculosis.
You might be happy to learn that you're actually an important part of that process as Futility
Closet is one of the podcasts I listen to during the more repetitive parts of preparing materials for screening assays, and I've recommended it to several colleagues.
To your original question, there are still drugs whose targets and mechanisms of action remain unknown, though there's usually groups of scientists working on figuring it out.
There are generally two ways to screen compounds for activity. The first is called a phenotypic screen, where you start with the organism or cell type
that you want to affect, add the test compound, and see what happens. In my lab, we're looking
for something that stops M. tuberculosis from growing. In the second, a target-based screen,
you start with an isolated protein, enzyme, or gene and see what compounds affect it.
The first approach doesn't
work for all organisms or diseases as you need to be able to grow the organism or cell in a lab,
and that can't always be done. And we can't yet model very complex diseases. The second is limited
because even though you may be able to block the activity of something in a lab, doesn't necessarily
mean that the effects will be the same in the patient, especially with diseases whose processes
aren't completely understood. For example, targeting certain enzymes in the pathway that produces
cholesterol or those involved in Alzheimer's disease have never produced successful results
in clinical trials, despite looking very promising in the lab. My lab has different groups pursuing
both types of screening, but I work primarily with phenotypic screening. We start with a chemical
library and test a single concentration against M. tuberculosis to see if it stops it from growing, Thank you. we analyze the resulting data, it gets sent to our chemist who group the active compounds together by similarities in their structures and remove any that are unlikely to be good drugs. We then
retest the compounds, as well as some structurally related compounds that we didn't initially test,
at several concentrations to confirm that they do prevent growth and do so at a low enough
concentration that they could be turned into drugs. If they pass that test, then we send the
data back to the chemists, who with the help of some drug design software make analogs that may improve their activity.
And Lindsay explained that after the analogs are retested, they go into more specialized assays
that model various situations because an ideal drug candidate needs to work under a variety of
conditions. Meanwhile, other researchers are working in parallel to try to figure out the
target and mechanism of action to help determine whether to continue work on the test compound
and to help guide potential modifications. Compounds that do well in the assays are then
tested in animals. Any compound that doesn't do well in the animal testing might be modified and
then sent back through the entire process from the start. And Lindsay says, only after that,
if the compound has a strong
portfolio of good assay results and activity in animal models, is it ready for clinical trials.
Between the preclinical development and clinical trials, it's not surprising that it takes between
10 to 15 years to develop a successful drug. The entire process is very long, complicated,
and repetitive, and it's a large part of why drugs take so long to develop and are so expensive. I've started this job almost five years ago, and some of the drug
candidates I've worked on have only started to progress into animal trials. Many more projects
on groups of compounds were killed because they didn't show good activity in later tests or had
side effects that were unacceptable. Out of the hundreds of thousands of compounds we've screened,
we'll be lucky to get a handful of successful drugs. And as another listener pointed out, repurposing existing
drugs is a big area of research since you can skip over the lengthy and costly preclinical work.
Thank you for all of the work you do on the podcast. It's the best thing about Monday mornings
for me. That's a very sensible way to go about doing that. And I'm impressed at how much work
it takes. But it seems to rule out, you know, just some eureka moment out of left field where
you come up with some completely new idea. Like this is very systematic. Right. But you wouldn't,
using that technique, it seems like you wouldn't come up with some just completely novel way of
attacking the problem. Although I guess we're well past the days when that's even possible. These
problems are so complicated. Yeah, and maybe some drugs, I don't know about a drug coming out of
left field anymore like they used to, but certainly with these repurposing, you suddenly discover that
a drug could be used for something that you hadn't expected. What really struck me about Lindsay's
email was I had mentioned in episode 196 about how a study found that only 9.6% of drugs that started human clinical trials made it through the clinical trial process.
And according to her email, only a tiny percent of compounds even make it up to the human clinical trials.
So it's like such a minuscule percentage of compounds actually make it all the way through
the process.
Yeah.
So you can see why it's so expensive.
And on the topic of how little we understand some drugs, Lindsay directed me to some blog
articles written by Derek Lowe, who has a PhD in organic chemistry and has worked for
several major pharmaceutical companies.
One of Lowe's recent articles, for example, was about how poorly antidepressants are understood.
He said, I was talking with a colleague the other day who's done a lot of work on central
nervous system disease over the years, and it reminded me of something that I said years ago
on this blog, that we don't know jack about how central nervous system drugs work. I'm still
willing to stand by that one,
although it's certainly true that there are some drugs
and some categories of drugs that we understand a bit better than others.
And Lowe explains that most people think
that it's well understood how antidepressants work, but it is not.
The general understanding of lay people is that
these drugs work by affecting serotonin levels
in the central nervous system, or CNS for short.
But he says, the unofficial motto of all CNS research is,
it's actually a lot more complicated than that, and so it is in this case too.
And Lowe notes that response rates to all antidepressants are variable and unpredictable,
that many patients have partial responses at best,
and that the efficacy of newer drugs is not
provably better than the older ones, which to me suggests that we don't know enough to produce
better antidepressants than the ones we've had for many decades now. Though I should say that
the newer ones might be safer than some of the much older ones. Lowe says that one of the big
issues is that we just don't know a lot about the illness in question. He says, if we knew more
about what was happening in the brain during depression,
we might be able to do better.
What happens on a neuronal level when a person has an onset of major depression?
Despite a great deal of work on this question,
we still have to throw our hands up in the air.
And Orion Sauter wrote,
I just listened to episode 196,
and the list of medicines discovered by accident reminded me of my own experience. I'm a survivor of brain cancer, And we're glad to hear that it worked out for you, Orion, but I
found it rather surprising to learn that mustard gas, which has caused so much misery for so many
people, was actually the origin of the first anti-cancer chemotherapy drugs. I tend to associate
mustard gas with World War I, but it was actually an incident in World War II that sparked this discovery. 100 tons of mustard gas had been stockpiled on the SS John Harvey,
which was in the Italian port of Bari in December 1943 when the ship was destroyed by German
airstrikes. While there were surprisingly few direct fatalities, many of the survivors developed
the symptoms of mustard gas exposure, and research on these victims resulted in the discovery of compounds
that prevent the normal sequence of DNA replication,
which became the basis of an effective treatment targeting rapidly growing cancer cells
that I'm sure Orion and many other people have been thankful for.
That's an amazing story and kind of ironic that it would yield such a great benefit.
Yeah.
An amazing story and kind of ironic that it would yield such a great benefit.
Yeah.
Tom Permut wrote in about the examples from episode 196 of how an incorrect understanding of a mechanism of action can still lead to an effective treatment, with another amusing example from history.
In the 17th century and earlier, there was a belief by some that a wound would heal better if you applied a dressing to the weapon that had caused the wound rather than to the wound itself. Some who tested this treatment actually found it to be more effective, which sounds kind of surprising. Though, as British
mathematician Augustus de Morgan said, if we remember the dreadful notions upon drugs which
prevailed, both as to quantity and quality, we shall readily see that any way of
not dressing the wound would have been useful. And given that there was no concept of antisepsis at
that time, and that traditional treatments included things such as chicken excrement or
cow dung, I think that De Morgan is quite right that not treating the wound for any reason at all
probably would have been preferable. That's a good insight. Often, sometimes the best treatment is none.
And similarly, Paracelsus, the 17th century Swiss physician and alchemist, describes treating
wounds with the herb persicaria.
First, you draw it through a fresh stream, and then you place it on the body part that
you wish to cure for as long as it takes to eat half an egg, which is a rather
interesting way to measure time. And then you bury the herb in a humid place so that it can rot,
and the wound will heal in the same time that it takes the plant to decompose. Paracelsus says,
it is not necessary to make the sign of the cross over the wound or to pray because it is a natural
action working naturally, not superstitiously or magically beyond nature.
And Tom says, again, burying the herb was probably more effective than leaving it on the wound.
Tom also said, humility is called for though. Our present theories will be as ridiculous to scientists of the future as Paracelsuses are to us. They're not right. They just account more or
less for the limited facts we know.
And I completely agree, because if history is any guide, then a certain amount of what we know or think we know will turn out to be rather wrong. The real difficulty is that at this point in time,
we just don't know which those things will be. So thanks so much to everyone who writes into us.
We are always sorry that we can't read all the email we get on the show, but we do appreciate hearing what you have to say. So if you want to say
something to us, please send that to podcast at futilitycloset.com.
It's my turn to try to solve a lateral thinking puzzle. Greg is going to give me a strange
sounding situation and I have to work out what's going on, asking only yes or no questions. It's my turn to try to solve a lateral thinking puzzle. Greg is going to give me a strange-sounding situation,
and I have to work out what's going on, asking only yes or no questions.
This is from listener Stephen Jones, and I've altered it a little bit.
World War II fighter pilot Douglas Botter lost two legs,
but this made him a more effective pilot. Why?
Is it because he would fit in a smaller space?
No. That's a good guess okay um
he lost two legs he lost his own legs like his limbs yes okay he lost the legs of a chair or
something okay um so he was piloting airplanes even though he didn't have his legs. That's right.
Did he have something in the place of his legs, like some kind of prosthetics that I need to know about?
I actually don't know that and tried to find out.
I know he used artificial legs on the ground, and I can't quite tell whether he used them in the plane, but it doesn't matter.
It doesn't matter.
So not having legs made him, what did you say, a more effective?
A more effective pilot, and I'll say in particular'll say, in particular, a more effective fighter pilot.
A more effective fighter pilot.
Because he had to develop his upper body strength.
No.
Okay, let's see.
What do you need to do to be an effective fighter pilot?
So you would say he shot down more enemy planes?
Yeah, he was amazing, by the way. I was already, before Stephen suggested this, he was on my list for potential podcast stories.
He had an amazing career for all kinds of reasons.
But this one detail is pretty interesting.
Maybe you'll have to do a feature on him anyway,
because now I want to hear more about him.
Yeah, no, really.
I think I might.
Okay, so would you say that if some other person
had lost their legs, they would have been
a more effective fighter pilot too?
Yes, for the same reason.
For the same reason.
And it's not that it made, is it because they're smaller in any way?
No.
Lighter?
They're lighter now?
No, that's not.
But more effective because you've lost your legs.
Boy, I don't see this at all.
Okay, what do fighter pilots have to do that that just regular
pilots don't have to shoot down enemy aircraft right and i would think you would use your eyes
and your arms for that yeah no it's not that so much um they get into fights with other planes
right was it something about like if he had to eject out of the plane? No. It would be better?
They get into fights with other planes.
I can't see that he would be less visible to other planes.
No, no.
But doing that can be very physically taxing.
Yeah?
It's physically taxing?
Yeah. Like if you're in a dog fight or just an air fight with other fighters.
Okay.
I don't know much apparently about being a World War II fighter.
So it's less physically taxing if you don't have your legs.
It's not because he needs to be in better physical condition because it's harder for
him to get around normally on the ground?
No.
No.
It's more that pilots who do have legs have a disadvantage.
Do they now?
That he's not vulnerable to.
Their legs cramp up?
I'm trying to think what disadvantage you would have.
I mean, I'm sure legs could be all sorts of disadvantages.
I'm just trying to think what they would be.
If you were in a dogfight or just an aerial fight with other bombers and doing complicated maneuvers at high speed.
Okay.
Your...
Legs would get in the way somehow.
No, it's that you're experiencing a lot of G-forces.
Okay.
And if you're a person with legs, that can be a problem.
That can be a problem.
And it's not because your legs cramp or something.
problem. That can be a problem. And it's not because your legs cramp or something. No.
I guess I don't know what the effects of G-forces are on you. Boy, I feel really deficient in my fighter pilot skills here. So does he stay in his seat more easily? No. It has to do with
his circulation. Oh, because the blood ends up in your feet
if you have feet for the blood to end up in
normal pilots if you're under
or at least fighter pilots in certain situations
oops
cat just tried to jump up
cat tried to jump up and fell
if the g-forces are strong enough
it can force the blood into your legs
and away from your brain
and you'll black out
wow I had no idea
Potter had no legs
so he wasn't vulnerable to that so the blood couldn't get as far away from his head and it'll black out. Wow, I had no idea. Botter had no legs, so he wasn't vulnerable to that.
So the blood couldn't get as far away from his head.
And it's thought that for that reason,
he could pull off maneuvers that other people couldn't
because he wouldn't black out.
Wow, that's a good puzzle.
I had no idea.
And I learned something.
Yeah, so I'll probably, as I say,
do a feature about Botter
because that's just one part of a really fascinating life.
So I'll hope to do more about that later.
Anyway, thanks, Stephen, for sending that in.
Thank you.
And if anybody else has a puzzle they'd like to send in for us to try, please send it to us at podcast at futilitycloset.com.
That's our show for today. I should mention that no animals were harmed in the making of this
week's lateral thinking puzzle. Sasha just can't always jump quite as high as she used to be able to.
But if you would like to help us keep her fully supplied
with catnip and toys she can play with on the ground,
then please check out our Patreon page at patreon.com slash futilitycloset
or see the support us section of the website at futilitycloset.com.
While you're at the site, you can also graze through Greg's collection
of over
10,000 concise curiosities. Browse the Futility Closet store, check out the Futility Closet books,
and see the show notes for the podcast with links and references for today's topics.
If you have any questions or comments for any of the three of us, you can email us at
podcast at futilitycloset.com. All the music in our podcast was written and performed
by my phenomenal brother-in-law, Doug Ross.
Thanks for listening, and we'll talk to you next week.