In 1856, after yet another day of disappointing experiments, a chemist named William Henry Perkin was cleaning up his glassware when he made a discovery that would harken a new — and colorful — era of science and industry. Just 18 years old, Perkin was a promising young student in a prestigious lab at the Royal College of Chemistry in London and he was supposed to be figuring out a way to make a chemical compound called quinine. Despite his best efforts, Perkin was coming up empty — or rather — producing a lot of dirty dishes with little to show for it. But he did notice that there was a curious goop in one of his flasks, and it turned a brilliant shade of purple in the wash. Intrigued, Perkin decided to try dyeing a swatch of silk with his serendipitous solution. Although he had failed yet again to produce quinine, Perkin had created the very first synthetic dye and launched a scientific industry that is still bringing new drugs and dyes to market today.
Transcript of this Episode
Sam Jones: In 1856, after yet another day of disappointing experiments, a chemist named William Henry Perkin was cleaning up his glassware when he made a discovery that would harken a new — and colorful — era of science and industry.
Just 18 years old, Perkin was a promising young student in a prestigious lab at the Royal College of Chemistry in London and he was supposed to be figuring out a way to make a chemical compound called quinine. At the time, quinine was a frontline treatment for malaria, scarlet fever, and other serious ailments, but the only way to get it was by extracting it from the bark of cinchona trees. Chemists in the 1800s were still pretty inexperienced with the nuts and bolts of building molecules from scratch. So despite his best efforts, Perkin was coming up empty — or rather — producing a lot of dirty dishes with little to show for it.
Deboki Chakravarti: But he did notice that there was a curious goop in one of his flasks, and it turned a brilliant shade of purple in the wash. Intrigued, Perkin decided to try dyeing a swatch of silk with his serendipitous solution. He had failed yet again to produce quinine. Instead, Perkin had created the very first synthetic dye and launched a scientific industry that is still bringing new drugs and dyes to market today.
Welcome to Tiny Matters, a science podcast about the little things that have a big impact on our society, past and present. I'm Deboki Chakravarti and I'm joined by my co-host Sam Jones. In today's episode, we're going to explore a few of the ways that modern organic chemistry and human medicine can trace their roots back to dye manufacturing in the 19th and early 20th century which is really just fascinating and news to me.
Sam: Oh same. I had no idea and I’m super excited to dive into this.
So, back to the 1800s. Perkin’s dye would later be named mauveine, sometimes also called mauve or aniline purple. You may be thinking “ok it’s just a dye, we have so many dyes today.” But it's important to remember that prior to the invention of mauveine, almost all of the world's dyes, drugs, and other chemicals were still extracted from natural sources. Like quinine. In the 1850s, people had figured out how to isolate quinine from cinchona bark to mix in wine or tonic water that you could purchase at your neighborhood apothecary to ward against malaria or treat a fever. But said apothecary might just as well whip up a tincture from actual powdered cinchona bark, and maybe a tiny bit of opium for good measure. So there was strong interest among scientists to try to bypass nature and make drugs by hand.
Deboki: And when you visited the apothecary, you were likely wearing clothes dyed blue with indigo plants from Asia or red with crushed cochineal beetles from Central America. But probably not purple. Purple pigments mostly came from mollusk mucus, making them so rare and expensive that only the rich and royals could afford them for their finery. And according to John Lesch, a historian of science and emeritus professor at the University of California Berkeley, Perkin decided to skip out on the rest of his studies. Instead, he filed a patent for his synthetic purple dye and opened a factory right outside London.
John Lesch: You might compare him to the people who do startups today. I mean, another thing to realize about Perkin is that when he made this initial discovery, he was 18 years old, so he was just a student in the College of Chemistry, but he immediately saw the commercial possibilities. And you might say synthetic organic chemistry was one of the high tech fields of the late 1800s along with electricity, say, for example.
Deboki: His company was wildly successful, especially after both Queen Victoria of England and Empress Eugénie of France made public appearances in mauveine-dyed gowns to great fanfare. Perkin amassed a comfortable fortune, retired from manufacturing at the age of 36, and went back to doing academic research for the rest of his career, John says.
Sam: I turned 36 this year and um… let’s just say I’m not looking at retirement any time soon! Very different trajectories! It was a different time. Mauveine’s success was no mere fluke of fashion, according to organic chemist Luke Lavis. Luke is a senior group leader at the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia.
Luke Lavis: It seems mundane to us now, just the colors in our clothing. But back then it was big business and Perkin recognized the opportunity.
Sam: And his discovery basically changed the focus of organic chemistry because…
Luke Lavis: Perkin showed that these compounds that were made by organic chemists could have commercial value. And so dye chemistry really dominated the field for the next few decades.
Deboki: By the turn of the 20th century, the chemical manufacturing industry was booming with multiple companies contributing their own technicolor creations to a growing palette of artificial hues. A great example is Friedrich Bayer & Company, which was founded in 1863 as a partnership between a businessman and a master dyer in Germany.
That name may sound familiar because it was the predecessor of today's international biomedical and agriculture conglomerate Bayer – which is also the first company to introduce aspirin back in 1899.
Sam: I think that’s what I think of when I think “Bayer.” But it’s pretty wild that they started out by making dyes.
Deboki: And Luke even pointed us to a Bayer Company sample catalogue titled "Shades on Feathers" that was probably published between around 1913 and 1918. Each page has a column of vibrant feathers next to a description of the products used to dye them. It’s actually really beautiful. The Science History Institute hosts a digitized, high-resolution copy on their website that we’ll link to in the show notes. If you look carefully, you may notice a few dyes that are still used today, including the pinkish red rhodamine dyes that you'll hear more about from Luke later in the episode.
Sam: Yeah, like I can see that some of these yellow entries are samples for tartrazine, which is marketed today as the food coloring Yellow No. 5.
Deboki: I was pretty surprised to learn just how many food colorings originated from this time period! Which brings us back to this question of how the chemical industry goes from developing dyes in the late 1800s to manufacturing pharmaceuticals today.
Sam: There were a lot of factors that contributed to that shift, which historians of science continue to study. So John laid out some of the top line items for us. Economic incentives were high on that list. The dye market was often in flux, so chemical manufacturers realized they needed to diversify their product lines to stay profitable. Luckily, many of these companies already employed skilled synthetic organic chemists.
John Lesch: And that was one reason they turned to pharmaceuticals, for example. But there are other products as well that came along, photographic products, fertilizers and pesticides and so on. So this brings us up to the late 19th century. And you have private corporations, especially in Germany, the big synthetic organic chemicals companies developing very strong scientific establishments with hiring PhDs, setting up laboratories, and developing a system for innovation of dyes initially, but then it quickly expands into drugs and other things.
Deboki: And this is right around the time that scientists were beginning to study infectious diseases. Remember that Perkin got his patent for mauveine in 1856. It was around this same time that the renowned chemist and microbiologist Louis Pasteur discovered that fermentation was caused by bacteria.
Sam: Louis Pasteur as in the guy who invented pasteurization, the process where we sterilize milk and other dairy products by heating them up and killing off bacteria or other pathogens that may be floating around, which I will note is a very important thing to do. OK, Deboki, please continue.
Deboki: Yes, exactly, pasteurize your milk. And he didn't demonstrate the first pasteurization procedure until 1863. So as organic chemists were really honing their molecule-building tools, biologists were connecting the dots between dozens of diseases and the microbes that cause them. And what were researchers using to identify all those new microbes?
Sam: Microscopes?
Deboki: Yes, exactly. So chemists were making molecules in almost every color of the rainbow, biologists were finding oodles of new germs that make us sick, and physicians were looking for effective ways to kill those germs without harming patients. Eventually, these groups realized that they could help each other out because some of these dyes seemed to stain only one type of cell while others in the same sample remained untouched.
Sam: Now, anyone who’s ever separated their laundry into lights, darks, and whites knows that some colors stay put better than others. For colorants to hold fast in fabrics, the dye molecule and textile fibers have to have chemistry.
Deboki: I see what you did there.
Sam: Yeah, not corny at all… And some dyes are picky about what types of surfaces they’ll stick to. Like a dye that's bright in wool and silk, which are made of protein, might look pale and faded if it’s on cellulose-based materials like cotton and linen.
Deboki: So a German doctor named Paul Ehrlich took this idea and ran with it. Over the course of his career, Ehrlich developed an expertise in staining tissue samples by applying dyes that would make specific structures more visible under the microscope. In one instance, he noticed that a synthetic dye called methylene blue could selectively stain the parasites that cause malaria, which are single-celled microbes in the genus Plasmodium. But more importantly, it appeared that the dye was also fabulous at killing these parasites while leaving the surrounding cells unharmed. In 1891, Ehrlich and his colleagues showed that the dye was effective at treating plasmodium infections in two patients suffering from malaria.
Sam: Historian Wallace B. Mendelson describes the saga in his book, Molecules, madness, and malaria: How Victorian fabric dyes evolved into modern medicines for mental illness and infectious disease. This dye-turned-drug was widely used both to prevent and treat malaria in World Wars I and II, but methylene blue did eventually get replaced by more effective medicines, which is good because according to Mendelson, it came with some unpleasant side effects, like it would turn the white of patients’ eyes blue. Which sounds kind of cool looking but also creepy? And I actually don’t know if there were additional side effects to that so… best to keep the whites of your eyes white I guess.
Deboki: Yeah I don’t know how I feel about that kind of side effect.
Sam: This was also just one of many instances where Ehrlich demonstrated that a synthetic chemical agent could treat an infectious disease – a strategy that he would later call “chemotherapy.” Following this chemotherapeutic approach, Ehrlich would go on to invent the first synthetic antimicrobial medicine to cure syphilis.
Deboki: People obviously use the term “chemotherapy" very differently now, especially in an age where we treat all sorts of discomforts with drugstore chemicals. But in the early 1900s, it was a ground-breaking concept that had droves of scientists digging for drug candidates in dye catalogues, especially medicines that could treat bacterial infections. Here's John Lesch again.
John Lesch: Bacterial infections were a major problem, and there wasn't much that could be done. They were what you would call self-limited diseases often that you would give basic nursing care and try to create a good diet and nutrition and other conditions for a patient, but basically the disease would have to run its course. There were all kinds of attempts to treat bacterial infections, but generally they didn't succeed.
Sam: In 1927, executives at IG Farben Industry, a chemical manufacturing conglomerate that included the Bayer company, chose a German research physician named Gerhard Domagk to lead a chemotherapy lab with a focus on pathology and bacteriology.
John Lesch: He was very interested in the infection process and how that worked. And so he had various projects going, but one of the things that he did was to set up an experimental model for bacterial infections, especially streptococcal infections. It was in mice that he would infect mice with lethal doses of streptococcus and then try different compounds out against them.
Sam: Domagk partnered with two chemists, Fritz Mietzsch and Josef Klarer, to test hundreds of compounds for their ability to eradicate streptococcus and staphylococcus bacteria from cell cultures and living mice. Among those compounds were Azo dyes, which typically range in hues from yellow to red, and are named for their characteristic nitrogen-nitrogen double bond, or azo bond. After promising preliminary results, Mietzsch and Klarer did what chemists do best: tinker. Using the structure of the first azo dye as inspiration, they made a bunch of different versions with subtle molecular modifications – like the addition of a sulfonamide group that makes azo dyes better at sticking to wool.
John Lesch: And lo and behold, one of them turned out to have a strong effect on streptococcal infections in mice.
Deboki: With a bit of fine tuning, Domagk and his team landed on a red-colored compound called Prontosil that was not only effective against strep infections but also a variety of other diseases too. This was the first sulfonamide drug — or sulfa drug for short — and they filed for a patent in 1932.
Now anyone who has ever worked in drug discovery knows that experiments in mice do not guarantee success in human patients. Lots of people were selling panaceas at the time, some of them leading to mass poisonings. So Domagk was cautious about pushing Prontosil into the public sphere until more clinical data was available.
Sam: That’s pretty smart. And kinda unique.
Deboki: But shortly thereafter, Domagk's own 6-year-old daughter Hildegard contracted a life-threatening streptococcal infection after nicking herself with an unsterilized needle. Mendelson writes in Molecules, Madness, and Malaria that, quote, "When it seemed likely that her arm would have to be amputated, the desperate father gave [Prontosil] to her, and within a week she was on the way to recovery.
Sam: Well, glad that one ended on a happy note.
Deboki: Yeah for sure, and despite his promising anec-data, Domagk kept this particular event under wraps until he could publish his full study in 1935, at which point Prontosil was officially granted its patent, John says. And while it took some time for people to overcome their skepticism, prontosil gained popularity after it successfully cured President Franklin Roosevelt's son of a severe strep infection. There were even news articles about it in TIME magazine and the New York Times. In another important development, researchers at the Pasteur Institute in Paris revealed that prontosil is actually what’s called a prodrug, which is a drug that’s inactive until it’s in the body and metabolized into its active form.
Remember that nitrogen-nitrogen azo bond we talked about earlier? Once someone takes prontosil, the body cleaves that azo bond and breaks the compound in two. The half of the compound that keeps the sulfa group is a molecule called sulfanilamide, and it turns out that sulfanilamide is the true source of prontosil's infection fighting prowess, and it was later marketed under the name Prontylin. And according to John, not only was sulfanilamide easier to manufacture, it wasn't covered by an active patent either. So companies jumped at the chance to make their own sulfa drugs, including a very effective treatment against pneumonia called sulfapyridine.
Sam: Which also earned another celebrity endorsement and a write-up in TIME magazine for saving the life of British Prime Minister Winston Churchill not once but twice.
John Lesch: So that was really one of the major impacts of Prontosil was to be eclipsed almost immediately by sulfanilamide and then the derivatives of sulfanilamide that were developed after that.
Deboki: John wrote a book about how these medicines shaped the world we know today called The First Miracle Drugs: How the Sulfa Drugs Transformed Medicine.
John Lesch: I think in the larger picture, and this is what I argue in my book, that introducing the sulfa drugs in the mid to late 1930s had an enormous impact in the sense that it raised optimism and expectations about what could be done by systematic pharmaceutical research. And you can see it in the language of “miracle drug," which now has maybe a slightly inflated sound to it, because we know all the problems that come along with powerful drugs as well. But in the forties and fifties, it was quite, I think, unselfconscious that this was a new era of new powerful medicines that were going to transform the practice of medicine in different ways, which did in fact do that.
Sam: For his part, Domagk's contributions were recognized by the 1939 Nobel Prize in Physiology or Medicine. But World War II was already in full swing and the German government forced Domagk to decline the award money, though he would later receive the medal retroactively.
Deboki: And while many sulfa drugs have come and gone since the advent of penicillin and other powerful antibiotics, some of them are still frontline medicines.
Sam: Yeah! And one of the most commonly prescribed analogues is sulfamethoxazole, which is combined with a second antibiotic to make drugs sold under the brand names Septra and Bactrim. If you've ever had a urinary tract infection, there's a decent chance you were prescribed one of these drugs, both of which are on the World Health Organization's List of Essential Medicines.
Deboki: I'm still trying to wrap my head around what life must have been like before antibiotics and all the other essentials I keep stocked in my medicine cabinet.
Sam: Yeah, definitely. Sounds like truly a terrifying and much more painful time. Although I am grateful for non-sulfa antibiotics because apparently I am allergic. Or at least baby-me was.
Deboki: Me too, I think.
Sam: I think it’s a huge percentage, but we’ve got options at this point which is excellent. Science has come a long way in the time since Perkin was cleaning basically everything but quinine from his glassware. In fact, chemists did finally figure out how to synthesize quinine in 1944 and they’ve only gotten a whole lot better at making intricate, carefully crafted chemicals for basically any purpose. Which brings me back to Luke Lavis, the organic chemist we met at the beginning of the episode, because his lab specializes in the synthesis of fluorescent dyes for high-resolution microscopy.
Deboki: Fluorescence is a physical property whereby a molecule will absorb the energy from one wavelength of light and then emit it back in a different wavelength. If you've ever seen paint or clothing glowing under a black light, like at a classic 90s roller rink, that's fluorescence. Funnily enough, quinine is also a superstar in fluorescence history.
In a 1852 paper, Sir George Stokes sought to understand an observation of an earlier scientist in which a clear, colorless solution of quinine in water would glow a, quote, "beautiful celestial blue colour" under certain light.
Luke Lavis: Reading his old papers is really fantastic. So he did this very simple experiment where he boarded up a window leaving a little slit, and then he put a prism in that slit. And so he had a rainbow in this dark room, and then he had a solution of quinine. And as he moved it down from red all the way to Violet, and then what we now know is the ultraviolet, the flask suddenly started glowing.
Deboki: Stokes wrote that "it was literally darkness visible", a reference to John Milton's epic poem Paradise Lost, which reflects the profound nature of Stokes's discovery. You can actually witness this glow for yourself if you've got some tonic water and a black light, or a gin and tonic at a 90s era skating rink.
Sam: I can’t skate but I want to try that.
Deboki: Yeah and I don’t know that I could combine a gin and tonic with a skating rink safely.
Sam: No, sounds like a lot of spill, but hey you’d get that cool glowy spill all over the ground that people are slipping on.
Deboki: Exactly. Like so many of the molecules we’ve heard about in this episode, a lot of the fluorescent dyes that Luke works with, also called fluorophores, trace back to the 20th century dye industry or earlier. So they were readily available in the 1940s when the American biomedical researcher Albert Hewett Coons was trying to find a better method than tissue staining to look at really fine details in cells under the microscope.
Sam: Thanks in part to pioneering work by Paul Ehrlich, it was well established by then that our immune systems use specialized proteins called antibodies to recognize and stick to microbes as a way to protect us from infections. So Coons got the idea that maybe he could combine the fluorescent properties of common dyes with the highly-selective sticky properties of antibodies as a way to spotlight specific features in cells. Working with his team at Harvard, Coons took an antibody that binds to pneumococcal bacteria and added on a fluorophore called fluorescein isothiocyanate or FITC.
Deboki: Which is a variation of the fluorescein dye that was first discovered in 1871, and that still gives me nightmares because now all I can think about is being in grad school and hoping things would show up on the FITC channel of the instruments we used because that meant my experiment finally worked.
Sam: Exactly. And seventy years later, in 1941, Coons and his colleagues took the first images of fluorescently labeled bacteria in tissue samples using a newly invented microscope that measures fluorescent light. Today, we call these techniques immunohistochemistry and fluorescence microscopy, which both play a huge role in modern medicine, and helped Deboki and me finish grad school.
Deboki: Which is really the most important contribution. Medicines, molecules, and microscopes have grown ever more sophisticated over the decades since. And while biochemists established new methods for delivering fluorophores to their desired structures within cells, like the discovery of genetically encoded fluorescent proteins, Luke says that fluorescent dyes remain remarkably unchanged. If you look in the lab fridge in a fluorescence microscopy lab, you’ll still see shelves stocked with fluoresceins, cyanines, and rhodamines — like the dyes used to make pink feathers in that Bayer catalogue Luke showed us.
Luke Lavis: One issue with these dyes is that they were first made in the 19th century. And so they were typically made using very harsh conditions, so concentrated sulfuric acid, very high temperature. And so really all but the simplest functional groups would fall apart under those harsh conditions.
Sam: Luke and his team saw an opportunity to take some of the sophisticated techniques that medicinal chemists devised to craft complex, tailored drug molecules and give these shabby old dyes a "glow up."
Luke Lavis: One of the things that my lab started doing was bringing modern chemistry to bear on some of these classic 150 year old scaffolds. And that allowed us then to expand the scope of these dyes and discover new molecules, with improved properties.
Sam: Properties like brightness and longevity, which means microscopists can use Luke’s new-and-improved dyes to run their experiments for longer periods of time before the dye loses its ability to fluoresce. And this can be used to, for example, follow a single molecule going about its business within a live cell.
Deboki: Luke is really excited about what we’re already learning from single-particle tracking experiments. For example, one of his collaborators at Janelia is a group leader named James Liu who studies a neurodegenerative condition called Huntington's disease that interferes with the parts of the brain that control voluntary muscle movements. People with Huntington's disease have a genetic mutation that causes the Huntingtin protein to stick together in clumps, eventually killing the affected cells and getting in the way of a lot of critical functions.
Luke, James, and their colleagues wanted to zero in on how the faulty aggregates interact with the normal, or wild-type, Huntingtin proteins within living cells in a petri dish. So they labeled the mutant version with green fluorescent protein, which clump together in a glowing mass. For the healthy Huntingtin protein, they used one of Luke's fancy new dyes that is so bright that their microscopes could track each individual protein and even make videos of its movements.
Luke Lavis: And the cool thing is you could see not only did the mutant Huntingtin protein aggregate that was expected, but you could also see the interactions with the wild type Huntingtin protein, and you can see those molecules slow down in the presence of this mutant aggregate. And so that really shed light on the intricate interplay. Not only are you getting aggregation with the mutant hunting and protein, but it's also affecting the wild type protein. So that I think led us down a path of recognizing that this type of imaging could be really important to understand disease.
Deboki: In fact, the aggregates slowed down several different kinds of proteins within the cells, making it harder for them to move about their business.
Sam: This is really important and cool on multiple levels. Because for one, this kind of super-resolution microscopy where you can basically take pictures — even videos — of where one individual protein is going in a cell … that's mind blowing. And then there's the information that we can now gain from figuring out what those proteins are up to.
Luke Lavis: And the beauty of that is you can add your molecule and then you can watch and visualize even subtle changes in protein movement. And then hopefully that will be an important way where we can discover new medicines.
Deboki: Now Luke and his collaborators are developing ways to apply these techniques towards drug discovery so that it's no longer just about "does this molecule kill infected cells or inhibit a specific protein" but "does this molecule change the way proteins interact within diseased cells". They've even launched a company called Eikon Therapeutics to use these new technologies for drug screening at an industrial scale. This work is gaining traction and other researchers have also taken up the torch, using new tricks to teach old dyes to shine bright in a new age of discovery.
Sam: Okay, it's Tiny Show and Tell time. So Deboki, there's a new gene editing tool in town.
Deboki: Oh, no. I mean that's great. I don't know why I said "oh no!"
Sam: Because we've gotten some CRISPR whiplash.
Deboki: Yeah, yeah. No, I still remember being in grad school when CRISPR came out and it felt like everything changed. And so I just immediately flashback to, oh, no, what are we going to do that involves CRISPR?
Sam: Yeah, no. It's called STITCHR. And the idea is that it will insert therapeutic genes into specific locations within a chromosome without causing unwanted mutations, like off-target effects. The idea is that this overcomes the challenge of probably the best known gene editing technology, which is CRISPR, which really is primarily used to go in and correct individual mutations. And there have definitely been studies that have shown off-target effects for CRISPR. Again, STITCHR is newer. Without causing unwanted mutations, that's the goal. I'm not saying that it's perfect, it's definitely not. I would bet my life that it is not perfect. Why would you want to be putting in a whole therapeutic gene as opposed to just popping in with CRISPR and getting rid of some mutations? For some diseases, one that I read about as an example would be Duchenne muscular dystrophy.
I guess the therapeutic gene, it's massive. It can't fit inside the viral vector that's used for gene delivery. What STITCHR does, is it'll actually split the gene into two pieces, delivers them separately using two viral vectors. And then it actually uses machinery within the cells, including ribosomes, to join the fragments together creating a functional gene. Which, I was like, that's very cool. But now, the reason I'm bringing this up is because I saw there was a story that came out yesterday about how researchers are talking about how this also could be very important for diseases where there are multiple gene mutations.
You could imagine that CRISPR could be used for a lot of things where you just have a massive gene. But let's say there are a bunch of mutations in that gene. We've talked a lot recently, I feel, about one mutation that actually causes essentially the entire phenotype, the disease. There are obviously many diseases where you're not just talking about one mutation, you're talking about a bunch. As opposed to CRISPR, where there's established concern of off-target effects, and where you're going in and you're correcting these mutations more or less one by one, scientists are arguing that STITCHR could be more of a one-and-done approach. Where you're going in, you're replacing a gene with the therapeutic version, and then you're out of there hopefully without off-target effects because you're doing a complete replacement. That's what I want to share with you today.
Deboki: That's cool. And I like the name. I like a STITCHR.
Sam: Me too.
Deboki: Yeah, that's really cool. Thank you. I hope that works really well for a lot of these challenges that happen with these therapies.
Sam: I know. It seems like it has a lot of potential. I'm going to be staying tuned, for sure.
Deboki: Yeah. I have some news for you about the shingles vaccine.
Sam: I think I know what you're going to tell me, and I'm excited. Go ahead.
Deboki: Perfect. I was about to say that it might not have to do with what you think would have to do with, which is shingles. Because we're not going to talk about shingles, we're going to talk about dementia. Which is that according to a new study, if you get the shingles vaccine you are 20% less likely to get dementia in the seven years after the shot. It could go beyond that, the research doesn't know yet, but the length of the study followed it for seven years.
Sam: Wow.
Deboki: Shingles is what happens when you get infected by varicella zoster. That's chickenpox when you're a kid. But one of the things that can happen is it can stay buried dormant in your nerve cells and eventually get reactivated when you're older. The shingles vaccine... I always think of vaccines as a thing you get as a kid, other than flus and flu shots or whatever that you get yearly. But shingles vaccine is actually a vaccine that you would get when you're older, because that's when you're potentially at risk for the reawakening of varicella.
Everything I'm about to say comes from this New York Times article about the study, which did a great job of summarizing what they did. I'm not going to go fully into detail, because I think it's one of those things where it's worth reading the original article. But I thought the design of this experiment was super fascinating. Because one of the issues with trying to study, hey, does taking the shingles vaccine make you less likely to get dementia? Is that there's so many confounding factors to that. Maybe there are other aspects of their life that is just healthier that's also contributing to them not getting to dementia.
But in 2013, Wales did a rollout of the vaccine that had this really funny age cutoff. Where if you were 79, you had a year to get the vaccine. But if you were 80 and older, then you couldn't get the vaccine. Because there weren't enough of the shots, and they also thought it wouldn't be as effective for people older than 80 so they just had this cutoff. And this created a really interesting set of experimental groups on accident for the people who were doing the study, because it meant that you had people potentially really, really close in age who you could compare for the effect of the shot.
Basically, the researchers, they went through the records of people who were between the ages of 71 and 88 when the shot became available, and saw over the next seven years who got the shot and what was the dementia rate happening? And in particular, they focused a lot of their stats on people who turned 80 the week before it became available, or who turned 80 the week after it became available. Because they're so close in age, they're probably similar in a lot of ways. And so that helped mitigate a lot of factors that might come up in terms of confounding these results.
Sam: That's smart.
Deboki: Yeah. I just thought that's just really interesting as an accidental experiment. They also looked at other things like how often people went to the doctor, would that have affected take medications? They did a lot of other work too. I just found that really interesting. There have been some other studies as well that supports this idea. Another interesting aspect of it is that because this is from 2013, I think I said, that was the rollout of this vaccine, they were actually using an older version of the shingles vaccine. There's actually a study last year that showed a more recent version might be even more protective. We don't know why, but there are a few possibilities. One might be that it reduces inflammation that happens when you get that virus reactivating, so that might be good for preventing dementia. Maybe getting the immune system activated might help to protect against dementia. Those are some of the theories. But, yeah, I just think that's-
Sam: Fascinating.
Deboki: There's so many cool things to this.
Sam: Very cool. Awesome. Thanks, Deboki. Thanks for tuning in to this week’s episode of Tiny Matters, a podcast brought to you by the American Chemical Society and produced by Multitude. The exec producer of Tiny Matters is me, Sam Jones. This week’s script was written by Ariana Remmel and edited by me, Deboki, and Michael David. It was fact-checked by Michelle Boucher. Our audio editor was Mischa Stanton.
Thank you to John Lesch and Luke Lavis for joining us, and to friend of the pod Kerri Jansen for her insights about Victorian apothecaries. A reminder that we have a newsletter! Sign up for updates on new Tiny Matters episodes, video clips from interviews, maybe a sneak peek at upcoming episodes, and other science content we really think you’ll like. We’ll see ya next time.
References:
- Reconstructing the historical synthesis of mauveine from Perkin and Caro: procedure and details .
- History of Bayer
- Shades on Feathers
- Louis Pasteur
- Paul Ehrlich
- Molecules, Madness, and Malaria
- Gerhard Domagk
- Medicine: Prontosil
- Young Roosevelt Saved by New Drug
- Medicine: Admirable M&B
- The First Miracle Drugs
- Sulfamethoxazole and trimethoprim (oral route)
- WHO Model Lists of Essential Medicines
- Albert Coons: harnessing the power of the antibody
- Real-time imaging of Huntingtin aggregates diverting target search and gene transcription
