On March twenty third, nineteen sixty three, at one a m. Jerrol Lynn Hilliman woke up with a sore throat. Five years old, with penetrating blue eyes and an adorable pixie haircut. Jerl quietly tiptoed into her father's bedroom and stood at the foot of his bed. Daddy, she whispered. Hillman shook himself awake, rose to his full height of six feet one inch, bent down, and gently touched the side of his daughter's face. There, at the angle of her jaw,
he felt a lump. Jerrel winced in pain. At the time of his daughter's illness, Hilliman was a single father. Four months earlier, his wife, Thelma, had died of breast cancer. Although he wasn't sure what was happening to Jerrel, Hilliman had a pretty good idea. Near his bed was a book titled The Murk Manual, a simply written compendium of medical information. Thumbing through it, he soon found what he was looking for. Oh my god, he said, you've got
the mumps. Then Hilliman did something that few fathers would have done. He walked down the hallway, knocked on the housekeeper's door, and told her that he'd be gone for a while. Then he went back to his bedroom, picked up his daughter and put her back to bed. I'll be back in about an hour, he said, Where are you going? Daddy asked Jeryl to work, but I won't be long. Hileiman got into his car and drove fifteen
miles to Murk. He rummaged around his laboratory, opening and closing drawers until he found cotton swabs and a vial of straw colored nutrient broth. By the time he got home, Jeryl had fallen back to sleep, so he gently touched her shoulder, woke her up, stroked the back of her throat with a cotton swab, and inserted it into the vial of broth. Then he comforted her, drove back to work, put the nutrient broth in a laboratory freezer, and drove home.
Most parents thought that mumps was a mild, short lived illness, but Hilliman knew better. He was scared aird about what might happen to his daughter. Although he knew that it was too late for gerald, Hillman wanted to find a way to prevent mumps. He decided to use his daughter's virus to do it.
It's a level good it's so exciting. It's amazing.
I also just love what a nerd he was that he slept next to the murkmanual like had it on his bedside table.
Maurice, it's amazing. As if you don't do the same thing, Aaron coming, I have a.
Stack of medical books on my bedside table right now.
See.
Yeah, I know it's embarrassing. Nerds unite.
That amazingly written story is true. Story is from the book Vaccinated, One Man's Quest to Defeat the World's Deadliest Diseases by Paul Offitt, and it is about Maurice Hillman, Yeah, who played a big part, a huge part, a crucial part, as well as his daughter in the creation of the momp's vaccine, which is the subject of today's episode.
It sure is. Hi.
I'm Aaron Welsh.
And I'm Aaron Allman.
Updyke and this is this podcast will kill you.
We're really excited to be bringing back yet another of the vaccine preventable diseases.
We sure are. I mean, this is the last of the MMR that we needed to cover.
Mm hmm yeah. The other M. We've got it, the other M.
Yeah, speaking of the other M, what are we drinking this week.
That's what we're drinking the other m M.
I feel like most people when they think of MMR, it's sort of all blurred together, right, it's measles, mumps, rebella. You barely take a breath between them or ye apause it's just all one word. But I also kind of think that maybe measles springs to mind first for most people.
I think it depends on the generation. I think that there's a good chunk of people who remember mumps more than anything because of some of its distinctive signs. But yeah, measles I think steals the show in that vaccine.
Yeah, maybe it's because of there have been more recent outbreaks of measles, although there have been recent outbreaks of mumps done. So, yeah, we are drinking the other m in any case, And in the other m it's a tasty little concoction with bourbon sage, simple syrup because my garden has way too much sage, and some orange tossed in there.
Yeah, delicious, I can't wait. It's very early fall.
Fantastic and we will post the full recipe for the quarantini as well as the non alcoholic plusy Brita on our website this podcast will kill you dot com as well as on all of our social media channels.
We sure will on our website this podcast will kill you dot Com. You all know how many amazing things you can find there. Do we even do this anymore? We've skipped it a few times. Check out our website.
I like it, and I don't think there's any more business. So can we dive into the last of the MMR.
I am really excited to do it.
Let's take a quick break and then we'll get into it.
So mumps mumps. Mumps is the disease.
That's the name of the disease that's caused by a virus that is named the same thing, the mumps virus, which I think we've covered a number of viruses whose disease.
Are named the same thing.
But I don't know why I expected mumps virus to be named something different, like something more virus sounding.
That's a good point.
Yeah, the mumps virus, it causes mumps.
What I mean, surely it has like a virus family and oh stuff like that. That sounds a little more professional.
We can do that. Of course.
It's in the family paramixa Viridae. There we go, which is, as it turns out, the same family as the measles virus, as well as parainfluenza, canine dis temper rsv a whole bunch of other viruses that are pathogenic to humans as well as our dogs. Mumps virus has a single stranded RNA genome.
It's an enveloped.
Virus, so outside its little protein capsid, it has this lipid and glycoprotein envelope that helps it evade.
Our immune response.
And from what I could tell, there are at least twelve different genotypes of this virus that do vary geographically, but it's unclear whether these genotypes vary that much in virulence, probably not substantially, at least as far as we know so far. Zero type wise, If you remember in our dosporosis episode, I talked a little bit about the differences
between like what is this zerotype, et cetera. Right, So, zerotypes are things that vary based on their outside surface proteins, and so we can categorize them based on different epidemic outbreaks and things like that, based on different zerotypes or zero VARs. And in the case of mumps, it doesn't seem like there are a lot of different zerotypes, but
there are differences in their genes. So there are different genotypes, but it's unclear how much these genetic differences really translate to differences in the virus and how it interacts with our immune system and causes disease, if that makes sense.
Yeah, okay. So, for instance, when it comes to different zerotypes, you might not have cross protection or as much cross protection from one compared to the other because the surface protein is different, and your immune system might not recognize a different zerotype that you haven't previously been infected with different genotypes. You could be infected with one and then your immune system would recognize another because of surface proteins aren't substantially different.
Right exactly.
Yeah, okay, Okay, that's it, more succinct summary than my blathering.
Yeah. I feel like I went on and on, but I think that that makes a lot of sense, and I think that's really interesting from both a public health perspective as well as an evolutionary perspective.
Yeah, yeah, exactly, And vaccines and vaccines.
So, mumps is a human specific virus. It does not infect other animals naturally, just humans, and it's a very contagious disease the rn not, which we haven't talked about for a long time.
I'm excited to bring it back.
The rn knot is a number that is used in epidemiology to estimate the average number of infections that result from a single infection in an entirely susceptible population.
I feel like we all know are not from COVID now.
I know.
Now it's been two and a half years, so people might have forgotten, you know what I mean? But yes, little refresher, But this is an estimate, so it can vary, right, depending on the population and the study that you're doing. So four months, the average is estimated at around four point four, so every one case results in four and a half ish additional cases. But depending on the population, that can vary from three to ten. Wow, yeah in
different studies. So potentially up to one person can infect up to ten people in some studies.
Ah okay, that's very contagious.
Very contagious. And transmission is by primarily respiratory droplets as well as close contact in general, because respiratory droplets are generally close content tech transmission as well as potentially foam mites or surfaces like door knobs, or pillows or whatever that become contaminated.
And that would be contaminated through your saliva exactly.
It's very much like influenza.
And how durable is this virus in the environment?
Great question.
I actually didn't see any data on that, so I do not know. Okay, yeah, yeah, good question though, But yeah, it can be transmitted that way. So it's very much like influenza and a lot of other crowd diseases that we've covered. And also, like a lot of those diseases, people become contagious or infectious at least a day or two before their symptoms start. And virus has been isolated from saliva and nasal mucosa up to a week before symptoms start, w which is terrifying.
Yeah, h okay.
Question how long is the incubation period?
The great question. It's very long.
It's between fifteen to twenty four days, so like two to three weeks.
That is so interesting. Why is it so long?
I don't know, arin I have a lot of I don't knows about mumps. So once we get exposed to the virus, let's say a couple of toddlers at preschool breathing on.
Each other like they do yeap.
The virus then predominantly infects the cells that line our respiratory tract, or at least initially begins to infect those cells, especially the upper respiratory tract. Usually doesn't make its way into our lungs, not causing like a lower respiratory infection. And then one of the primary cell types that it infects and begins to replicate within is our parotid glands. Our parotid glands are a pair of salivary glands in your cheeks, kind of like back near the angle of
your jaw. And this infection of this glandular epithelium that's the cells that are lining the glands like in your parodid glands, leads to what's called a paratitis that just means inflammation of these glands, and that is what leads to one of the hallmark symptoms of Mump's infection, which are super super swollen cheeks. But this is not a virus that only infects our parodid glands. It can infect
a variety of glandular epithelial cells. It can infect our respiratory epithelium of course, it can infect our central nervous
system and wherever it goes. What it does is essentially replicate a lot, and this replication causes a lot of local inflammation infiltrates of our white blood cells trying to fight off this virus by killing those infected cells, which can then lead to hemorrhage or necrosis of various tissues within these organs and significant swelling and potentially increased pressure
in these various glands. So what we see with infection with a mumps virus is both direct damage from the virus replicating in ourselves, but also a lot of indirect damage from our immune response to such a highly proliferative virus.
Okay questions, Okay, why does it go where it goes, especially like the central nervous system and outside of the salivary glands and respiratory tract.
Great questions.
So what's very interesting is that one of the papers I read suggested that mumps virus actually has a very high We've talked on this podcast about tissue tropisms, so particular tissue types that viruses are very good at infecting, and in animal models, mumps virus actually has a very wrong tissue tropism for nervous tissue, so it invades and replicates really well in nervous tissue in animal models, but
in humans we actually don't see very common. It's not the hallmark symptom to have neurologic involvement, as we'll talk about, you definitely can, but primarily it seems to infect these other epithelial cell layers. Why does it have a particular tropism for these glandular epithelial cells. I don't have an answer for you. And what's very interesting is that it really is these parodied glands specifically that are the hallmark and other salivary glands. Because our parodids are not our
only salivary glands. We have others under our mandible and under our tongue. Those tend to not be infected at least not without also having parodid gland involvement. Like it's much less common. Does that make sense?
Yeah?
How fascinating.
Yeah, And I will talk about this isn't restricted to that glandular epithelium. It can infect epithelial cells in a lot of other organs as well, And I think it just as a matter of does it manage to make it all the way to those organs evading our immune response on its way there and then if it does, then it can set up shop and just replicate like it does in our parodids.
One more quick question, Okay, how does infectivity change throughout the duration of infection?
Yeah, you're most infectious those couple of days before symptoms start and then for the first week ish after that. Okay, Yeah, but we know that virus can be detected for up to a week before symptoms, and I think for even longer than a week after symptoms begin. But the most highly infectious time seems to be that kind of more narrow time window of just before symptoms start and for a few days maybe up to a week after. Okay, yeah, so let's talk about what those symptoms actually look like,
shall we. Yeah, just talked about this virus itself, talk about what's happening to us. So first of all, and this kind of like messes up what I just said Aaron about the product lands. But thirty percent of the time this is an asymptomatic infection, right yeah, yeah, which I did not know, and I feel like it makes it that much more terrifying considering how long the incubation period is, how much you can shed before symptoms even start,
how much are asymptomatic carriers contributing to spread. Ooh scary, but yeah, okay, but that's thirty percent. So let's talk about the other seventy shall we? In that seventy ish percent of people who become symptomatic, the infection usually starts with a little bit of a fever, but not like
I'm laid out, I'm feverish, I'm so ill. It's just like feeling right down, maybe not having much of an appetite, often having a headache, feeling sick, and then over two to three days is when that hallmark sign of paratitis begins. The parotid glands can get so big that they actually lift up your ear lobe kind of up and out,
and you completely lose that angle of the jaw. If you look at pictures of people with mumps, it it's hard for me to describe well, but you just really have two ginormous chipmunk cheeks.
Also, if you've watched Brooklyn nine to nine, there's an episode oh where Jake and Captain Holt get mumps. Yeah, I forgot about it, and they name them. They name their big swollen lumps.
That's hilarious. How accurate is it. Well, let me go through and you'll tell me.
I can't. I mean, it's been a long time, but it's it's yeah, it's been a long time since I've watched it, but yeah.
And this swelling can persist for up to an entire week, and it is incredibly painful. It's a very very inflamed organ. It's super tender. Ninety percent of the time, it's bilateral, so you're miserable on both sides, and usually it starts on one side and then the second side takes a couple extra days to come in.
That part is accurate from Brooklyn nine nine. Oh sure, I love that.
And ninety five percent of people who show symptoms do have this paratitis, so it is very, very classic. The testes are another very common sight of Mump's infection, especially in post pubertal people with testes. Fifteen to thirty percent of post pubertal people with testes can get an infection that is often an epididymmo orchitis. Oh gosh, it's both epididymitis and orchitis.
So let me tell you what those two things are, shall we? Yeah?
Yeah, So these symptoms often start several days to a week after the paratitis.
It is possible to get it without.
That parodid gland swelling, but it's much less common and it's two different things that can happen. First, it's an orchitis, which is inflammation of the testes themselves, the sperm producing little oval structures in the scrotum. With that inflammation, think of it just like your parodid glands. It's swelling, its warmth,
its tenderness, extreme tenderness because of all this inflammation. Then on top of that, you can also get an epididymitis, which is inflammation of the epididymis, which is the tube that carries sperm away from the testies themselves and kind of stores the sperm as well. And with that you usually also see more general constitutional symptoms like a worsen fever, headache, vomiting, just overall looking a lot sicker. So that's very miserable.
In terms of the long term effects of this epididimo orchitis, it seems still controversial from what I could tell, whether there is a long term association with like infertility or subfertility or reduced sperm production. There are some studies that do suggest a small decrease in testicular size and or abnormalities in spermatograms, whether that be sperm count, sperm morphology,
or sperm motility. But this is only in a percentage of people, and it doesn't seem like we have great data on how common this is or what the real effects of this are, Like why is this causing.
More long term effects?
Ovaries can also be affected, but it tends to be much less common. About five percent of post pubertal or reproductive AID people with ovaries get oopharitis, So again just inflammation, same situation happening, but in the ovaries. You have a question, like your face is saying like why and I don't know why?
So, yeah, why is it less common? Is really what I was gonna ask.
I wonder if it has anything to do with like differences in body temperature or something like the testes and the salivary glands are in a very different place in your body, in your abdomen, But I don't know, because they can also replicate in your kidneys just fine. So maybe it's just that it's a more indirect route to try and get there for the virus.
I don't have an answer for. Yeah, do we just diagnose it less. I don't know, I don't know. I don't have an answer.
Interesting now, all of those symptoms are horrible, they're painful. They may or may not cause residual symptoms in the case of an architis or an epidemitis, but they do tend to be self limiting in all those cases. The problem with mumps virus is that it can also infect the central nervous system, and it can result in a
meningitis or an encephalitis. It is rare. Most estimates I saw suggested that about five to ten percent of cases of mumps will cause a meningitis, although one World Health Organization articles suggested up to fifteen percent and less than half a percent point five percent cause encephalitis, which is the worst one.
Five to ten percent still seems pretty dang high.
It is absolutely and apparently up to half of the time with a meningitis. It can happen even without that parodied land swelling and infection, so you might not have had that as a preceding symptom. To know that this meningitis is likely related to the mumps, if that makes sense, and if that's not enough that it can happen without even the product land swelling. It can also happen in any order, so you can see meningitis that starts before
salivary gland involvement or after salivary gland involvement. Okay, Now, mumps meningitis is a more severe infection. You can see things like high high fevers, headaches, vomiting, all the scary kind of meningial signs when you have inflammation of these mening's lining your nervous system, like stiff neck.
Like lethargy.
But in general, very low mortality from mumps meningitis and very little long term issues and problems that arise as the result of this meningitis, which is really in contrast to other causes of meningitis.
However, there's always a however, there's always a.
However, there can be a progression to encephalitis, which is inflammation happening in the brain itself, in the parankama of the brain, and that does lead to the potential for severe and lasting damage, including seizures, behavioral changes. Hearing loss asterisk Hearing loss is actually a well known complication of mumps that happens in about four percent of cases overall, so not only in these encephalitis cases, but unlike hearing loss as a consequence of other forms of meningitis, it's
often unilateral rather than bilateral one ear not both. And it's often transient, which is good, but it can be permanent, which is not good. And despite how rare this encephalitis is in a mump's infection, MOMPS was the leading cause of viral encephalitis in the United States and many other countries until the vaccine was widely available.
So this is not a.
Benign disease ease, even though the vast majority of people who get it will have a very sort of self limited disease course. So yeah, that's kind of the worst of the things that can happen. Like I kind of alluded to, mumps can infect a lot of other organs. It can cause a pancreatitis, which is inflammation in your pancreas. It can cause kidney infections, it can infect your heart. Really, it can go anywhere, but the ones I talked about are kind of the most commonplaces that we see mumps
infection happening. Overall, the fatality rate is very low, about one to three per ten thousand infections, and almost exclusively in cases of encephalitis.
I have a question. Okay, So clearly it can cross the blood brain barrier and cause problems in your central nervous system. Correct, can't cross the placenta great.
Question, I believe. So it's not very strong associations. But there is some suggestion that mumps can be associated with spontaneous abortion early pregnancy loss, even in a few case reports that I saw neonatal infection leading to neonatal death when someone was infected like very much at the end
of their pregnancy, like a few days before delivery. So yeah, But part of the problem about kind of all of these questions is that most of what we know about the pathogenesis of mumps comes from animal models, and this is a human.
Specific virus, So all these animal.
Models are imperfect, and I think it's probably a part of why we don't know maybe as much about the specific pathogenesis as we do about other viruses.
Right, Okay, that makes sense.
But we do have a vaccine.
We do.
It's the second m in the MMR vaccine measles, mumps and rubella.
The vaccine for.
Mumps is a live attenuated vaccine, which means it's a live virus that has been grown in laboratory culture to not be virulent, so it doesn't cause symptomatic disease, and it's available in MMR, but also as like on its own, just mumps. And there's actually a lot of different vaccine strains that exist out there, and some of them do seem to be more effective than others, which is very interesting, especially in the context of the fact that we don't know that genotypes.
Are all that different, you know what I mean.
And what's very interesting, and I'll kind of talk more about what has happened as a result of this. Some cases of aseptic meningitis, so meningitis that.
You can't grow anything from, like in.
Culture, have happened as a result of vaccination with specific strains of the vaccine of the mump's vaccine. But this vaccine isn't really in use very commonly anymore because of that. And importantly, all of the cases of asymptic menindritis that happened from this vaccine strain of the virus did not result in any kind of long term consequences or any deaths as far as everything.
That I read, Okay, but important to note, Okay.
I have a question about the disease itself.
Okay, heps.
So you mentioned that in infants the disease can be very severe. Do we see any other patterns when it comes to age, for instance, in terms of whether someone has certain symptoms or more likely to have a more severe course of infection stuff like that.
Yeah, great question. It actually tends to be more severe, like a lot of childhood illnesses if you get it later in life, so as an adolescent or adult, especially with testes, because we really don't see that testicular infection prior to puberty very commonly at all.
Right, okay, So then that leads me to a question about the vaccines, which is waning immunity. How does the vaccine durability change across these different vaccine strains.
That's a great question, Aaron. The whole waning immunity thing is a really important part of vaccination. So in general, childhood infection with mumps induces a very persistent, long lasting immunity that, as far as we know, is pretty much lifelong. But again, infection can also cause meningitis, encephalitis, and death, so we vaccinate to avoid those consequences. Vaccination with mumps specifically does seem to have a waning immunity.
Although.
It's not forevery on average, some studies have found that vaccination can lead to twenty seven years or more of immunity to mumps, which.
Is a really long time.
Yeah, but up to twenty five percent of people might lose that protection within just seven or eight years. Okay, So the twenty seven years is an average, but that average has a really widespread and the question of why that is is something that we still.
Don't really know.
Okay, And I'll talk a lot more in the current event section about what the consequences of that have been in terms of outbreaks that we've seen in adolescents and young adults especially that likely this waning immunity plays.
A big role.
Yeah, of course, So that's a biology of MOMPS.
What a weird little virus, isn't it. It's interesting though, It's really interesting. Yeah, So tell me erin where did this weird little guy come from? I won't answer that question, but I'll get into more about months and the history of this disease right after this break. Months is a classic. It's a classic TPWKY topic. Historically, it's been a classic childhood illness and now thankfully it's a class vaccine preventable.
Disease such a classic.
It's a classic, and most of what I'm going to talk about today is the story of the Mump's vaccine, as well as the man behind this and many other vaccines, Maurice Hillman.
If you're a listener you know his name.
You certainly do. But before I get there, I want to briefly take you through the early history and prehistory of mumps, or at least as far as we know. Where the mumps virus came from seems like somewhat of a difficult question to answer. It's possible that it's spilled over from pigs to humans during the agricultural Revolution, when humans first began to domesticate pigs, and that's based on the fact that there's a very similar virus found in pigs.
They seem to be related. Or another option is that it's spilled over from humans to pigs.
Ah maybe.
And more recently, a virus very similar to the human mumps virus has been found in certain bat species, leading some researchers to hypothesize that perhaps the mumps virus spilled over from bats into humans and maybe also pigs. This is kind of my long way of saying that.
We don't know, we don't know, we don't.
Know where mumps virus came from and when it first started infecting humans, and maybe that information is out there and I just didn't search for it well, but I couldn't find anything more specific than that. But we do have a better sense for when mumps was first written about, and that is, of course, from the Hippocratic texts in
the fifth century BCE. Retrospective diagnosis of any disease can be difficult, in a little bit hand wavy, but as you described, a typical infection with mumps is pretty distinctive thanks to those chipmunk swellings around your jaw. And so this quote from the Hippoocratic text describing an outbreak of an illness on the island of Thasus seems pretty clearly mumps. Tell me if you agree, okay. Quote swelling appeared about the ears in many on either side, and in the
greatest number on both sides. In some instances earlier and in others later, inflammations with pain seized, sometimes one of the testicles and sometimes both.
Yep, sound sounds like sounds like mumps.
Yeah. And in later centuries, historians and physicians recorded outbreaks of a disease that sounds pretty similar to mumps, and as early as seventeen fifty five people suspected that it was contagious.
I just love I love those stories when people knew that it was contagious, before they knew, like what the heck a virus or a bacteria or anything was.
What was the actual contagious agent unit?
Yeah? Oh yeah, yeah.
And by the way, I just have to throw and hear the etymology of mumps.
Oh please.
So the English word for the disease mumps, it's different in other languages. The origin of that is a bit of a mystery. It could refer to like lumps around your face, okay, could refer to the English word mump meaning to be sulky. Or it's even been suggested that it comes from the difficulty in speaking experienced by people who have those salivary glandsucks like mumbum.
Yeah.
I don't know, but one of the things I thought was really hilarious, especially when you were talking about how like why doesn't the mumps virus have a more scientific sounding name.
Yeah.
So, one of the earliest articles about mumps, like scientific articles from seventeen ninety is titled quote an account of a distemper by the common people in England vulgarly called the mumps. So and the author, like in the text, immediately said like, I beg leave to call it not mumps but angina maxilaris HM. He was like, we can't call it mumps, it's too improper. So mumps is the
vulgar name for it. I guess who knows hilarious. But in anyway, by the late seventeen hundreds, interest in mumps had increased, with the result that people began to take a closer look at the more severe manifestations of infection,
like the nervous system involvement that you talked about. They also began to recognize its cyclic pattern, so every few years, like I don't know, three to seven years or so, an epidemic would occur as the number of susceptible individuals in a given area increased, which is something that we commonly see for crowd diseases, especially prototypically childhood diseases. People also started to note its global distribution, which was truly seemed to be global, and they also observed how it
spread rapidly under certain conditions. Things like prisons, boarding schools, ships, and of course soldiers at war. The estimate for some military populations was as high as six thousand cases per one hundred thousand individuals.
Wow.
That's pretty high.
It is.
And it's interesting that, like they're going to be grown ups. It's like there's that many people who were still susceptible in that population for that outbreak to happen. Yeah, that's interesting.
Yeah it is. Yeah, how did they escape it? I mean, yeah, they just missed the window.
They just missed the window.
Ooh, and unfortunately hit it later on.
Yeah.
I mean so during the US Civil War, about eleven thousand, two hundred cases of months were reported during the first year and over thirteen thousand, four hundred in the second.
Wow.
So again these are not these are people who escaped it as child children.
Yeah.
Mumps also ran rampant during World War Two, with the Surgeon General of the US Public Health Service stating in nineteen forty that it was quote one of the most disabling of the acute infections among armed forces recruits, seated only by the venereal diseases.
Wow.
Yeah, I had no idea how prevalent. No, this was, and I feel like a lot of people, a lot of us who were born after the mumps vaccine already existed, maybe just didn't realize how widespread it was. It was just sort of an inevitability, almost of childhood.
I feel like mumps has been one of the most brushed under the rug, like a vaccine came out, and then our collective consciousness like forgot how bad it was because I didn't know how bad it was.
I feel like the same thing. Maybe measles was like that too, until measles started increasing and people were reminded of just how horrible this disease could be. Maybe yeah, so yeah, but I agree, it does sort of seem like an afterthought, And it certainly didn't used to be just an afterthought. It used to be a hugely important disease, and that made it a public health priority to find out how it was transmitted and what caused it, what
was the pathogenic agent. In nineteen thirty four, C. D. Johnson and E. W. Goodpasture demonstrated that mumps was caused by a filterable transmissible agent aka a virus I love it in saliva, and they did this by transmitting the disease from humans infected with mumps to reesis monkeys, and a little more than ten years after that, the virus was first cultivated by k Havel and a few years after that, in nineteen forty eight, g Henley and his
colleagues investigated the relatively high rate of asymptomatic infections. Interesting apparently there was an experimental killed virus vaccine that came out in the early nineteen fifties, but I don't know if it was just if it stayed experimental, you know, or if it was ever distributed widely, And I'm kind of guessing that it wasn't because there was still such a need for months, was still infecting millions of people
every year, yea. And in order for months to become this afterthought, like we talked about simply like one of the ms in MMR in many places around the world, which it kind of is today, although things are changing, that transition would take a more effective vaccine, and for that we needed, of course, Maurice Hilleman.
Let's hear it for Maurice.
Let's hear it for Maurice. From the start of the twentieth century to the end of it, Americans lived thirty years longer on average, and that's thanks to an improvement in many different technologies and infrastructure, sure from seat belts to access to clean drinking water and improved sanitation, antibiotics, workplace safety regulations, improved in nutrition, and many other things.
But the most impactful of all medical advances was certainly vaccines, and the person responsible for developing a great number of these life saving vaccines was one Maurice Hileman. Like you said Erin, if you've listened to the podcast before, Maurice Hileman's name probably sounds familiar to you, especially if you've listened to our vaccines episodes, where we mention some of the incredible work that he did in vaccine research, but
we didn't talk about him in too much detail. And since this month's episode marks the last of the diseases covered by the MMR vaccine that we've done on the podcast, I thought I'd take just a little bit more time to talk about Maurice.
I can't wait.
Maurice Hillman was born at his family's home on the banks of the Tongue and Yellowstone Rivers near Miles City, Montana, on August thirtieth, nineteen nineteen. It's like Eastern Plains Montana, just out there. His birth was marked not only by global tragedy he was born at the end of the influenza pandemic that had killed tens of millions of people around the world, but also by personal tragedy. His twin sister died at birth, and his mother followed shortly after
from eclampsia. Yeah. Maurice later said, quote, I always felt that I cheated death.
Wow.
He spent his childhood living with his aunt and uncle, but working during the day at the family farm, the Riverview garden, and nursery, and getting into trouble and adventures when he wasn't working, nearly drowning in the Yellowstone River while floating on a makeshift boat, getting diphtheria, nearly getting hit by a freight train while riding his bike across a train. Yeah. Rough and tumble childhood. His childhood heroes were Charles Darwin he got caught reading on the origin of species.
In church, Oh my God.
And also Howard Taylor Ricketts, who I talked a lot about during our Rocky Mountain Spotted Fever episode. Yeah.
Ricketts of Ricketzia.
Ricketts of Ricketsia. He worked in Montana trying to understand how Rocky Mountain spotted fever was transmitted and the role that the tick played, et cetera, et cetera, and find the causative agent. As Maurice got to the end of high school, he struggled with what to do next. The thought of going to seminary school to become a preacher, which was a very common path at that time for people in his town, that didn't really appeal to him, and so he applied and got a full scholarship from
Montana State University. He graduated in nineteen forty one, first in his class, with a degree in chemistry and microbiology. His plans were to go to medical school, but he couldn't afford it, so he turned his sights to grad school. He applied to microbiology programs all over the country, and
his top pick was University of Chicago. He got into all of them, but he chose Chicago, where he quickly made impressive progress on his dissertation, discovering that chlamydio was not caused by a virus, as was the prevailing thought at the time, but rather a small intracellular bacterium. After finishing that up, the expectation from everyone at the university was that he would stay in academia, teaching and doing research,
but that didn't really sound great to him. Didn't sound as good as a job at a pharmaceutical company, because he wanted to take what he had learned in graduate school and apply it to industry. Be Able to scale up like vaccine production, be able to quality control stuff instead of just one project after the next, half for
the next Yeah. But the University of Chicago didn't want him to go into industry, and so they set up various obstacles to make it more difficult, including a French exam, and Maurice hadn't studied French, so he spent six months learning the language, passed the test, and finally was permitted to work at the pharmaceutical company er Squib in New Jersey.
Wait, I'm sorry, like they wouldn't give him his degree or something, until he hoops.
I don't know if it was like not giving him his degree or just I can't remember what the book said, but yeah, gosh, I know it's academiah. Yeah. And at Squib he worked on the mass production of influenza vaccines. After about four years there, he headed to the Walter Reed Army Medical Research Institute to try to develop new influenza vaccines, and that's something that would serve him very well when he led the charge to produce a vaccine
for the nineteen fifty seven pandemic strain of influenza. The nineteen fifty seven flu pandemic doesn't get a whole lot of attention, I feel, because maybe it wasn't as severe as the nineteen eighteen one, but what it did was demonstrate the potential for another influenza strain to sweep through populations, especially those that had no previous immunity to a similar strain.
And Maurice was not only one of the first in the US to recognize the potential for pandemic spread, but also he was able to get people to take it seriously, pushing for vaccine development when others were like, you know what, it's not here, We're going to be fine. We don't need to worry about it, and he was like, oh,
we absolutely need to worry about it. And part of the reason why the nineteen fifty seven flu pandemic didn't turn out to be as deadly as the nineteen eighteen one was likely due to the vaccine that Maurice produced and pushed.
Wow.
After the nineteen fifty seven pandemic, Maurice broadened his scope beyond influenza. He left Walter reed to become the Director of Virus in cell Biology at Murk Research Laboratories, and in his new position, he had one simple, easy goal to prevent every viral and bacterial disease that commonly hurt or killed children.
Oh, oh, my goodness, I know, super easy, right, like super simple, no problem, doesn't have like big goals or anything.
No, but honestly he got pretty close. Wow. He created and tested more than thirty vaccines over the next thirty years of his career, and one of those vaccines was, of course, for the subject of this episode, Momps Momps. As you heard in the first hand account, the mumps vaccine got its start when Jeryl Lynn Hillman, whose father was Maurice Hillman, came down with the infection in March
nineteen sixty three. Maurice took that throat sample that he had gotten from Jeryl and brought it into the lab where he set to work on trying to make a mumps vaccine. Not for Jerl of course, like was mentioned, since it wouldn't do her any good at that point. But for the rest of the world. During the nineteen sixties, about a million people in the US got infected with
mumps every year. And so when you were talking about these numbers arin of oh, well, five to ten percent of people get meningitis and then a smaller percentage of point get encephalitis, those seem like small numbers, but when you have millions of cases every single year, those are thousands of lives exactly.
That's the thing of about months.
Ninety five to one hundred percent of people will get mumps in their lifetime if they are unvaccinated, if the entire population is susceptible.
Yeah, so, like.
This is not a disease that only affects some people. It literally affects everyone in unvaccinated populations. And that's what it did until we had a vaccine.
Yeah. Yeah, those those percentage points can make the risk of diseases like this seem low. But when you have the number of susceptible people, first of all, the actual number of people impacting can be high. Second of all, no matter how low the risk is, if you can
avoid it, why risk it? Just yeah, I know, yeah, I mean, I think you know, like we've talked about many of us today don't maybe think about mumps all that often, especially those born after the vaccine was available, And I think our distance from that time period and mumps was a persistent childhood threat. Basically, an inevitability means that we don't recognize how fortunate we are to not have to think about mumps. We don't. We're like, oh,
we never think about mumps. It's brushed under the rug. How amazing is that. It's a wonderful thing. And so Maurice was not just thinking, oh, hey, no one's made a mumps vaccine yet, Guess I'll give it a go. This seems like a solvable problem, something fun. He knew that if he could successfully create a vaccine, he could save millions of people around the world from this potentially
harmful infection. And so he took jerald sample to the lab and he inoculated it into an incubating hen's egg, and then passed the virus into more eggs, and then grew the virus in chick cells that he had cultured. Again, he transferred the virus from one flask of chick cells to the next, seeing the virus get better and better At infecting the chick cells with every passage, and Maurice took this to mean that the virus was losing its ability to infect humans as it was getting better at
infecting these chicken cells. But perhaps even though it couldn't cause disease in humans, maybe it could induce an immune response enough for protection. This serial passage process that Maurice used had been used and has been used by many researchers for decades to make vaccines. It's how Louis Pesture
made the rabies vaccine, for instance. But how can you know for certain that the virus you've created using this process for any process, really is actually a effective at preventing infection while b not giving you the disease itself and c being safe.
Yeah, you have to test it out.
And this is where we come to the part of the story that is not surprising but still disappointing, frustrating, appalling, choose your adjective. But it's important to talk about, and that is the testing of vaccines and other medical studies in children with developmental disabilities. This was not an uncommon practice in the nineteen thirties, nineteen forties, nineteen fifties and into the nineteen sixties, including with Maurice Hillman's Moump's vaccine.
Paul Offitt, in his book Vaccinated, writes that from our perspective today, we may think of the scientists heading those studies as a moral viewing those children as expendable opportunities to conduct their studies, but he argues that these doctors really saw the children as more vulnerable, more in need of protection, especially those living in crowded and underfunded state
run facilities where infectious diseases often ran unchecked. And part of his reasoning to back that up is that many of these researchers, including Maurice Hillman, including Joe and A. Sulk, also tested the early versions of their vaccines on their own children, So why would they inject their kids with something they thought could be unsafe. I'm not sure that
I agree with that take entirely. I think it's likely that some researchers did feel that way, that they had good intentions with their studies and who they chose to test out those untested products on, but others may not have felt that way, may have truly looked at these children as less than or as dispensable, And maybe others didn't really think that much at all about the ethics
of this, beyond seeing these children as an opportunity. Administration of the vaccine and follow up was easy because they were all in one place. Infection rates were high, so you could get a good sense of how well these vaccines protected, and many of the children were wards of the state, so you didn't have to deal with the parents.
And my point here is not try to decipher what these researchers thought about what they did, whether their intentions were good or bad, or how they reconciled it with their ethics. And I'm also not going to go into the history of how we got from there to where we are today with much stricter guidelines on how these studies are conducted, who gets chosen or who gets asked to participate in the study in form consent and so on.
I'm also not saying, oh, it was a different time, everyone did it and no one thought much of it. And I'm also not saying progress could only have happened at the expense of these non consenting individuals, which is certainly not the case. So enough about what I am not trying to do. What I do want to do, what I want to get across is just that this happened. This is a crucial part of the history of the mump's vaccines, of polio vaccines, of hepatitis B virus, and
so many other things. When talking about the history of a disease or a medication or medical technology, we need to address the cost of progress and acknowledge who actually paid for it, which in many cases has been non consenting individuals. Where did the earliest data come from that showed that the mumps vaccine was safe and effective. It came from children whose consent was not or could not be given, and that should be a part of the
story we tell when talking about the history of mumps. Okay, so what happened? The first mumps vaccine test was actually a pretty small study. Sixteen children at the Trendler School in Pennsylvania, which was a home for developmentally delayed children, and these sixteen children were injected with Maurice's experimental mumps
vaccine in June of nineteen sixty five. The results were clear. Fortunately, the vaccine was both safe and produced antibodies against mumps, and so a second trial was carried out, this time on sixty children with developmental delays living at other schools, again demonstrating that the vaccine induced the production of antibodies against the MOMPS virus. But one thing still had to
be answered. Did this vaccine actually prevent disease? We saw antibodies, but were those antibodies enough to prevent disease from actually
infection from actually happening? And to answer that they had to scale up and for this, Maurice and his colleagues thankfully turned away from using these state run schools and instead, for several months, Maurice and his colleagues went around to preschools and elementary schools in the Philadelphia area and handed out flyers to parents telling them about this new vaccine and that there would be info sessions held at local churches.
At these sessions, researchers on the project would describe the vaccine, how it was made, a bit about how it worked, and then they would open it up to questions. If a parent was interest and allowing their kid to get the vaccine, they filled out a three by five inch card that said I allow my child to get a
Mump's vaccine and had a signature at the bottom. This was this three by five little index card was a far cry from the informed consent forms that you see today with info about the safety of the vaccine, the timeline of the project, a list of the ingredients, what the study would entail in terms of tests or follow ups, all the things that were known. But I found it really funny to read that it did include the home and work phone numbers of Robert Wibel, who was one
of the lead investigators on the project. Who's that call anytime you have any questions, any concerns.
That's good.
In total, about four hundred children were enlisted in the study, with two hundred getting the mumps vaccine and two hundred getting a placebo love it. Several months after the study began, a mump's epidemics swept through Philadelphia, and when the dust settled, sixty three children in the study had gotten mumps, two had been given the vaccine, and the remaining sixty one had not.
Wow.
Wa, pretty pretty good, Pretty clear.
Yeah yeah.
And on March thirtieth, nineteen sixty seven, a couple of years after this study and four years after jerro Lynn came down with mumps, the jerre Lynn mumps vaccine was licensed for use in the US, and cases of the disease dropped rapidly, and since that time, this vaccine has prevented millions, like countless millions of cases of mumps around the world. I want to read this quote from a reporter that has been widely circulated about the mumps vaccine
because I think it's hilarious. Quote Jerrel recovered from mumps virus, but mumps virus never recovered from infecting Jerrel.
I love it.
I love that within a few years, the mumps vaccine was combined with the measles vaccine also made by Hillman, and the rubella vaccine made by Stanley Platkin to be the one shot MMR vaccine we know today, and this was simply to reduce the number of injections that a child had to get.
There are more and more combo vaccines coming out because there are more and more vaccines.
More and more vaccines. It's awesome. This combo shot, of course, was the same that would later be falsely attacked by Andrew Wakefield, who did his best, along with many other people, to undermine the efforts of Maurice Hillman and others to keep children safe. If you want to hear more about the history of the anti vaccine movement and just how completely wrong and unethical Andrew Wakefield was is check out
Our Vaccine's Part two episode. And I'll also recommend the books Vaccine Sceanes Did Not Cause Rachel's Autism by Peter Hotez, our fave and also Deadly Choices by Paul Offitt. And there are many other great books and other resources out there, but please be careful where you find your information. Books aren't peer reviewed, and anyone can write a book and
claim anything they want to in it. And even though they aren't peer reviewed, there are reviews of non fiction scientific books that can often be found in academic journals, so it's a bit more homework, but I will recommend plugging a book title into Google scholar seeing if a review pops up, read the review to see whether it's good or not. I love that, Yeah, recommend anyway. Back
to Mumps and Maurice. Over the course of his career, Maurice Hillman and his team created tens of vaccines, including eight of the fourteen routinely used in US vaccination schedules measles, mumps, hepatitis, hepatitis B, chicken pox, niceria, meningititus, Streptoccus pneumonia, and Hemophilus influenzae. His vaccines have saved the lives of I don't even know if we have a number like countless people around the world and continue to prevent death and illness in
millions annually. His name and work really should be more widely known, at least as well known as someone like Louis Pasturer or Jonas Salk or Alexander Fleming. And that's a part of the reason why I wanted to spend a little time talking about his life and what led
up to the creation of the mumps vaccine. Unfortunately, several of the diseases for which Maurice developed these vaccines have been making a comeback over the last few decades due to a lack of access to vaccines, vaccine hesitancy or anti vaccine sentiment and waning immunity, and mumps is no exception. I so wish it were the case that the last chapter in the book of Monps was here's this life saving vaccine, everyone used it and Momps went away forever.
Sadly that's not the case, So Aaron, tell me where we actually stand. What the most up to date chapter is on months today and what college campuses have to do with it.
I can't wait.
We'll take a quick break and then I'll let you know. Turns out, Aaron, college campuses have a lot to do with it.
We're being honest, I thought, so.
Yeah.
While we've had a vaccine for MOMPS since, like you said, the nineteen sixties, MOMPS is not quite as common of a vaccine included in national immanization programs worldwide as things like measles, rubella, even polio. About fifty to sixty percent of countries, depending on which paper I read, include mumps in their national vaccine schedules. But in places where it has been very highly uptaken, I guess the effect was dramatic.
Finland actually eliminated mumps entirely in the country for a while and only had imported cases here and there.
It's so awesome. But also, your verb tenses are worrying.
I know, yeah, they're they're valid.
The US had a decline of like ninety nine percent. We were down in two thousand and one to less than point one case per one hundred thousand people. Like wow, from a million cases per year to less than point one per one hundred thousand people.
That is, it's so great and I hate where this is going.
Okay, Yeah, Since those numbers, which really I would say probably like peaked in the early two thousands in terms of overall effectiveness and decline of months cases, probably peak early two thousands, two thousand and one, et cetera. Since then, we have seen increasing numbers and an increase in sporadic outbreaks in the US, in Europe, which is highly vaccinated,
and across the globe. The reasons for this are very multifactory, and what's interesting about these outbreaks, especially in the US, is that they tend to actually be among vaccinated individuals and not unvaccinated individuals as we saw with measles outbreaks several years ago.
So it's likely that this.
Idea of waning immunity that we talked about in the biology section likely plays a really big role when it comes to months that it plays less of a role as we see with other infections. So think more like protessis, which is another one we've already covered. Waning immunity leading to segments of populations that are now newly immune and therefore you.
Can have an outbreak.
This has happened on college campuses because nothing's wrong with college campuses, but it's just a place where all of this huge group of people all got vaccinated at around the same time, some proportion of them had waning immunity at around the same time, and they're in close quarters sharing saliva.
And et cetera.
Now you have an outbreak, right for an outbreak. So in the US we had outbreaks in two thousand and six, twenty sixteen, twenty seventeen, in twenty nineteen that were.
All pretty big.
Most of those had case numbers of over six thousand in these outbreaks twenty it's a lot, And in twenty nineteen the outbreak was over three thousand.
Wow.
Not all of this was college campuses.
But a number of these outbreaks were associated with college campuses. Do you remember Aaron twenty sixteen Illinois.
I was living in Panama that whole year.
Oh well, it was University of Illinois and they were recommending MMR boosters for everyone.
I think I do remember that vaguely, remember the emails at least.
Yeah.
Worldwide, it's hard to get great numbers. There have been outbreaks like this that number in the thousands in the UK, in other countries, in Europe, in Australia. It's hard to get a number globally, but one paper that I read estimated an global annual average of more than five hundred thousand cases between twenty five and twenty ten.
Huh okay.
So it's not like this is a virus that we have even come close to eliminating by any means.
And it's human specific, so in.
Theory, in theory, in theory. Arin part of the issue I think has been, in addition to perhaps issues of vaccine access which always come up, a number of countries had initially implemented national vaccine campaigns and then made them more like a volunteer and not as part of the national vaccine program.
And part of.
This had to do with these cases of aseptic meningitis. And so I want to kind of get into this a little bit more, especially because there has been polio in the news recently and this kind of relates to what we have seen with polio as well. So let me get into this idea that viruses can cause infection. If you have listened to our polio episode, we talked a lot about the fact that there are two different polio vaccines in the US. We used to use an
oral polio vaccine across the globe. We used to use this exclusively an oral polio vaccine, and this is a live attenuated vaccine, highly effective. It was an oral vaccine, so easy to administer, and it replicated in our guts, which is how polio is transmitted its fecal oral So
this oral vaccine conferred really good protection. And it was also possible for people to shed this live virus through their feces, which meant you could have passive immunization of say, household contacts through this fecal oral root of a non virulent strain of this virus.
It's awesome.
It's awesome.
However, this non virulent strain can mutate potentially to become more virulent and actually cause disease, and so over time, as we massively decrease the number of polio cases, the risk benefit analysis of using this live attenuated vaccine shifted into the other direction, and so we no longer use the oral polio vaccine in the US and in a lot of other countries that have eliminated or greatly reduced polio.
We now use an inactivated, injected polio virus vaccine. That's what we use in most of the world now when it comes to mumps, this exact of events has not been shown to happen. We don't have things like passive immunization and that.
Sort of thing.
We haven't seen outbreaks from the viral strain the way that we have in cases of polio. However, there have been case reports of aseptic meningitis, so inflammation occurring in the me ninja's importantly, not encephalitis, not inflammation in the brain itself, but aseptic meningitis from some strains of the vaccine.
And so understandably this caused a lot of concern and led to the withdrawal of some of these vaccine strains and in some cases stopping vaccination for months entirely, or making it voluntary rather than part of a national immunization campaign, which has implications not only for like vaccine uptake and acceptance, but also a lot of times for funding. Countries don't fund it if it's not part of the national campaign.
Yeah.
One country where this happened, where these cases happened because of the particular vaccine strain that was used and then the national vaccine program stopped, was in Japan, and Japan now has one of the highest rates of months among high income countries, with over a million cases reported annually.
As of twenty fifteen. So that's a huge issue. Yeah yeah, WHOA, I know.
So I feel like what this comes down to, it's several different things. One, there are other strains of this vaccine, like the one that we use here in the US, that are not associated with aseptic meningeritis. I want to emphasize that the vast majority of strains that are used for this have not been associated with this and are very, very safe and well studied vaccines. The strains that have caused this generally are not used, and the cases all were,
while scary, self limiting. But I do feel like this kind of touches on something that I think is important when it comes to a disease like mumps and a vaccine like the mumps vaccine that was developed many years ago.
I think that this is a good example of why we can't be complacent, both in terms of like, we can't assume that a disease is gone just because we have a vaccine for it, right, Like, we don't know how long immunity is going to last when we come up with a vaccine, so it's quite possible that this could re emerge at a later date, so we shouldn't be complacent in that way. But we also shouldn't be
complacent in terms of the vaccine itself. We have a vaccine, it's very effective, though the immunity might not last as long as we'd like, and it can prevent morbidity and mortality. But can we make it better? Can we make it we're safe? Can we make it more effective, especially as we are doing such a good job of reducing the population disease incidents overall? Can we make a more effective
vaccine with less potential for side effects? So I think that that is kind of the place I'm most excited to see mumps research go in the future is towards maybe new vaccine research.
Yeah, but I don't have an update on where we're at with it.
No, But I agree that was really well put about complacency, Like there's yeah, we can still look forward. We don't have to be like, okay, like, yeah, our hands we're done.
When we can't forget where we came from and why it was so important to begin with, and why it's still so important to get this vaccine. The full picture, the full picture, so that Aaron is the mumm ups the momps.
Should we do sources?
We should? We should do some sources.
Okay, I have several, but I'm only going to shout out to. One is the Cambridge World History of Human Disease, the Months chapter, and the other is of course Vaccinated by Paul Offitt, which was also the source for our first hand account recommend great read.
I had one particular favorite paper for the biology section and that was titled Months Got eleven Yeah, from the Lancet in two thousand and eight. I had a couple of others for more details on the pathogenesis, and then a number of papers on the epidemiology of months, especially in the era post vaccines. So you can find the list of our sources from this episode and all of our episodes on our website did we tell you about it? This podcast will kill you dot Com.
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