This Podcast Will Kill You - Ep 26 Vaccines part 1: Let's hear it for Maurice

Episode Date: May 14, 2019

The wait is finally over: this week we are very excited to bring you the episode we’ve been teasing for weeks: vaccines! This week and next (you don’t have to wait a full two weeks for the next episode!), we are presenting a two-part series on vaccines. In today’s episode, we dive deep into the biology of vaccines, from how they stimulate your (amazing) immune system to protect you, to how they make you into an almost-superhero, shielding the innocents around you from deadly infections. We take you back hundreds, nay, thousands of years to when something akin to vaccination first began, and then we walk along the long road of vaccine development to see just how massive an impact vaccines have had on the modern world. The best part? We are joined by not one, but two experts from the Bill and Melinda Gates Foundation. Dr. Gail Rodgers and Dr. Padmini Srikantiah explain the process of vaccine development, highlight the challenges of vaccine deployment, and shine a hopeful light on the future of vaccines. And be sure to tune in next week for part 2 where we’ll focus on vaccine hesitancy and address common misconceptions surrounding vaccines in even more depth. For more information on the Bill and Melinda Gates Foundation initiatives, visit: https://www.gatesfoundation.org/For more information on vaccines currently in development, check out: https://clinicaltrials.gov/ and https://www.who.int/immunization/research/vaccine_pipeline_tracker_spreadsheet/en/And, as always, you can find all of the sources we used in this episode on our website: http://thispodcastwillkillyou.com/episodes/  See omnystudio.com/listener for privacy information.

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Fees, exclusions, and restrictions apply. See loaves.com slash appliance delivery for more details. Visit your nearby lows on Reneer Avenue South in Seattle. I am one of the increasingly rare old-timers who lived during the pre-vaccination era. I am the second to the last of 13 siblings, five of whom died of vaccine preventable diseases in infancy. Born to poor immigrant parents, I remember well my mother's account of the causes of their deaths, three from protesis, and two from measles. Even after many years had passed, she spoke of the death of her angels with a great deal of emotion.

Imagine losing not one, two, three, or four, but five babies. It was common in the pre-vaccine era. Like our family, many families lost several children to these diseases. We forget. Time blurs our memories of these common tragedies of yesteryear. I remember well during the winter and spring of each year, hearing the whoop of protusses and movie theaters, school assemblies, and assorted gatherings. Today, few have ever heard this, and those who have forget. I remember the summer outbreaks of polio, the crippled children who could no longer walk or walk with limb, distorted limbs. As the third and fourth year medical student, I remember answering the appeals of

appeals of hospital administrators who could not find the nursing staff for special duty tending to the needs of polio patients in iron lungs. We forget. I remember the awful cases of measles my own children experienced. I remember the children with smallpox during the years my family lived in Pakistan. I remember those who lost their sight from lesions in their eyes. I remember those who died. We forget. So that was a letter to the Immunization Action Coalition by E.J. Gene Gangorosa, who was a professor emeritus from Emory University. He wrote that letter in 2000. Wow. Yeah. It's it is amazing. He's, he's very right. We do forget. And, and those of us who have never heard it don't know. Right.

Yeah. We don't know what it's like. Right. My name is Aaron Welsh. And I'm Aaron Oman of Dike. And this is, this podcast will kill you. Vaccines today. Yes. This is the first episode of a two-part series on vaccines and all about the history of vaccines, the biology of vaccines, how they work. And we are also so thrilled for this episode because we got to talk to two real-life vaccine experts. Woo!

Dr. Gail Rogers and Dr. Padmini Shrikantaya, who are both senior program officers at the Bill and Melinda Gates Foundation. We chatted with Dr. Shrikantaya and Dr. Rogers about how vaccines are developed, some of the different vaccine-preventable diseases that are targeted around the world, and the challenges faced in some global vaccination initiatives. We had such a great time talking with them. Seriously, aspirational. Yeah, they've like lived lives that we want to live someday. It was so cool. And we know that you're going to love them too. So stay tuned.

Woo-woo. Okay. So what are we drinking today? It's, it's vaccine time. No, it's quarantini time. It's quarantine time. We're drinking. Wait for it. Ender's fame. Finally. Finally. Yes. So this this quarantini is named for John Enders, who is the recipient of a Nobel Prize for his work on cultivating the polio virus, which really paved the way to create polio vaccine. He also created the measles vaccine. I'm talking too much about the history.

Tell me what's in the drink. It's cognac, orange lique, and lemon juice. It's basically a sidecar. Yeah. Fancy little fun drink. And we'll have the full recipe for that quarantini as well as our non-alcoholic placebo Barita on all of our social media channels as well as our website. This podcast will kill you.com.

Yeah. Check it out. Check it out. We also, really quick, need to make a fun little announcement. We are working on an episode where we answer questions you send us about us or about disease ecology or podcasting or cocktail techniques or honestly whatever you can think up. Anything you want to know. So send us your questions by email to this podcast will kill you at gmail.com.

And if you decide to send us a question that you want us to answer for this episode, please put Ask the Erins or something to that effect in the subject line, and let us know whether you're okay with us saying your name on the episode. We can't wait to hear from you. All right. Should we just jump right into it? I think we should. Okay.

We'll take a quick short break. So, vaccines are often called one of the greatest public health inventions of all time, and I agree, they totally are, but it's partially because they work at two different levels. Vaccines work both on an individual level, so when you get vaccinated, you are protected against whatever infection you just got vaccinated against, which is great, who doesn't want to be protected. but they also work at the population level. So when you get vaccinated, you're actually protecting all of those around you as well.

So you can pat yourself on the back for doing a public service every time you get vaccinated. So to understand exactly how vaccines can be so awesome and work on these two totally different levels, I'm going to get into some serious detail about the biology and epidemiology of how they work. And I'm going to do it so that you can, A, understand how awesome our immune systems are. B, understand how cool it is that vaccines exist. And C, be the one who explains this to Aunt Martha at Thanksgiving this year. Oh, yeah. Okay. Excellent. All right. So to first

understand how vaccines can protect you, specifically, dear listeners, we first have to understand how our immune system works and how our bodies fight off infection. So immunologists don't hate me. I'm going to break this down in the simplest possible way. It's more complicated, but these are the basics. There are two major parts to our immune system. There's a non-specific, which is called the innate immune response. And then there's a specific response, which is called the adaptive response. Okay. The innate immune response, it's very fast on the uptake. When you get exposed to viruses or bacteria, it can find them and start to get to work really quickly, but it's not that powerful, it doesn't last that long, and it can't destroy everything. So we have a second immune response, the adaptive immune response. This is something that allows us to target very specific individual pathogens, but it takes some time. It's a little bit slow. slow to get started. So what that means is that before your adaptive immune response kicks in,

you usually get sick. You feel crappy. And then your adaptive immune system needs time to kick in and actually fight off that infection. But the good thing about this adaptive immune response is that it has a memory, like an elephant. It never, it never forgets. So anything that the adaptive immune response has responded to once the second time it's exposed to that same virus or bacteria, it can respond much more rapidly and much more effectively. Right. Okay. So here's how it works in four acts. We're going to have a play. Oh my God. Mine's in four parts too. Really? Oh my God. Yeah. We didn't even plan that. No, we didn't. That's thrilling. Oh, my goodness. Okay. So we're, uh, Biology play First 4X.

Here we go. So we have three main characters. Do you have three main characters too? I have a host of characters. Okay. Well, we're just simplifying it to three. We're going to have three main characters in our immune system play, the macrophages, the T cells, and the B cells.

Okay. All of these three characters are types of white blood cells. And in your body, you have a lot more than just these three. But these are our three main characters, and all of the rest of your white blood cells are going to be the ensemble. Okay. All right. Act one. You breathe.

Okay. In your breath, you inhale an antigen. This might be a virus, a bacteria, a toxin, your neighbor's boogers, aerosolized poop, whatever. Gross. Yeah, well, that's life. It's a foreign substance that doesn't belong in your body. And in your body, just waiting at the ready, are thousands, nay, millions of these white blood cells ready to jump into action. First, in comes the macrophages.

The macrophages are going to see this antigen, this virus or bacteria, and they're going to eat it. They're going to gobble it up. and they're going to take that and take a part of it, and they're going to bring it over to their friends who enter stage left, the T cells. And the T cells walk in, and they're like, hey, macro, has it going? What do you have for us today? And the macrophage is like, so I don't know exactly what this is, but I found it over there, and I know it doesn't belong here.

I recognize it. I'm not sure what to do with it. And the T cells are like, don't worry, we got you. Act two, we got you. So the T cells, they recognize that antigen. There's a whole group of these T cells. And they're like, we can do two different things. Some of these T cells, they're a little wacky.

They're a little wild. They're called the cytotoxic T cells. They probably have like a Mohawk and a motorcycle. Sweet. They recognize that antigen. They're like, I know, I know how to take care of this. Don't worry. So they're going to exit. And they're going to go start replicating like wildfire. And they're going to go out and just find anything that has that same antigen, any virus that looks the same, any bacteria that looks the same as that antigen.

And they're going to go out and kill it. They're just going to start murdering things throughout your body. Okay. All right. Shoot first, ask questions later. Exactly. So those are the side of toxic Mohawk T cells. The other T cells, they've got like bangs in a short bob, they're the helper T cells. They're a lot calmer. They're going to take this antigen and swing their way over to their friends who hang out at the lymph node bar, the B cells. And as they walk into the lymph node bar, they call out amongst the thousands of B cells just hanging out. And they're like, like, hey, hi, everybody. Does anyone recognize

this antigen? Macrophage just dropped it off. Do you guys know what to do with it? This is kind of your thing. And in through the swinging, what do you call those old-timey Western doors? Swinging doors? Swinging doors? You hear the

clink. Clown doors. There you go. You hear the clink, clink, clink of spurs and in-walks where an attention gallon hat a B-cell and he says I sure do I sure do recognize that antigen and then they get to work act three immunity so 10 gallon hat B cell he knows what to do he starts replicating and replicating making more and more copies of himself and inside he's making antibodies these antibodies are super They're going to target just that one antigen that the T-cell brought over. And these B cells are making millions of these antibodies.

And what they do is they throw them out into your bloodstream. They travel throughout your whole body. And they find an attached to that antigen anywhere that they find it. Whether it's in your cells that have been infected, whether it's on the bacteria or on the outside of a virus, anything that has this specific. antigen is going to get an antibody attached to it. It's kind of like a flag that you put on buildings when you say this one's going to get demolished and this one's going to get demolished. That's what an antibody is. So these antibodies go out and mark all of these cells so that the ensemble, the rest of

the cast, the rest of your white blood cells can recognize it. And now they can come in and clean up the mess. The little soldiers. Exactly. So they come in and destroy that infection. Okay, so can I just review? Absolutely. Okay, so the macrophage picks something up weird, and then they bring it over, and they're like, okay, everyone, T cells, B cells, what is this? So the T cells, the killer ones, they go and they just kill anything that remotely resembles that antigen? Anything that specifically resembles that antigen. Okay, specifically resembles that antigen.

What does that mean? specifically resembles. It means anything that is that exact same antigen. So it's not going to go out and just kill anything that looks similar to it. It'll just be that exact antigen. Okay. And then the helper T cells, they go and find the B cells and say, hey, this is what we're looking for. Can you go and tag everything? Exactly. And so then that makes the killer T cells job easier? Absolutely. Yeah. And it also brings in the rest of the white blood cells so that it's not just the T cells out there killing things. Okay. Act four. Memory. So once your body has done all this work and cleared the infection, it's not done. Old 10-gallon hat B-cell and a few of those wild cytotoxic Mohawk T cells, they're going to develop into memory cells.

These cells hang out and persist. They no longer run around making antibodies or killing cells. They're going to go backstage and wait until it's their time again. they'll play cards. They'll bide their time. And if that same antigen ever shows their face again, these B cells and T cells, the memory cells, will be able to jump right back into action. They won't have to go through the whole rigmarole of acts one, two, and three. They'll just be able to use the antibodies they've already have in the memory cells to make more copies and identify and target that antigen and quash the infection before it ever takes hold.

So this is the principle that vaccines exploit. They expose you to an antigen, which is a virus or a bacteria or part of a virus or bacteria, and that triggers your immune system to develop this memory response so that if you're ever exposed to that virus or bacteria in real life, you've already got a response ready to go. You don't have to take the time to build that immune response. And so the difference between that first exposure and then seeing that same pathogen again is a state of disease and then a state of rapid immune response and no disease. And then a vaccine just bypasses that whole disease. You don't have to actually endure the disease symptoms. Exactly. So if you imagine that your immune cells, in a lot of cases, if you're

they're dealing with a live virus, a full-on, fully loaded measles virus, it's not like they're just dealing with something passive. That virus has come in guns ablazing. It's replicating. It's going full force, while your immune cells might be kind of like tripping over their lines and getting things wrong and trying to figure out what to do about it. Right. So an immunization is kind of like a dress rehearsal for the play. It's real. There's people in the audience still. And you're going to develop the exact same response at the end of it, but you don't have a live virus trying to kill you while you develop this immune response the very first time. Cool.

Yeah. Cool. It's fantastic. I mean, vaccines are the best. So that's how vaccination can protect you as an individual. How does it protect an entire population? This is something we've touched on before, but it's called herd immunity. And it goes something like this.

Every infectious agent, bacteria, virus, fungi, whatever, in order to survive, it has to spread from person to person. That's how they reproduce. And in order to do so, in order to spread from person to person, there have to be susceptible people in the population for that virus or bacteria to get into. So if a population has a high level of vaccination, let's say like 97% of 100 people are vaccinated, that means that those 97 people have developed this immune response already. They're already protected.

So if you happen to drop an infected person in the middle of that population, the child. the chances that that infected person would run into somebody who's still susceptible to that disease are really, really low. So you'd have that one infected person who will get sick and then hopefully they'll recover or else they'll die from their infection. And then that's it. Nobody else gets sick because that sick person didn't run into anyone who was susceptible to that disease. But if you imagine that maybe only 50% of people are vaccinated, then only 50% of people are immune, and the other 50 are susceptible. And you dropped an infected individual in the middle of that population. There's a pretty good chance that that infected person will run into somebody who happens to be susceptible. And maybe

they cough or they shake their hand or lick their face. And now you have two infected people. And then that second infected person, they have a pretty good shot, like 49 more people, that they might run into another susceptible individual and lick their face. And now you have three infected individuals. Right. And so on and so on. So this is the principle behind herd immunity. If the entire herd, the entire population, or enough of it is immune to infection,

either because they've already been exposed and recovered from the disease or they were vaccinated and they developed immunity, then the infection can't spread. Right. So the more people that are immunized against something or immune to something by whatever means, the less chance that a pathogen has of establishing in a population or being transmitted. Exactly. So by getting vaccinated, you are protecting yourself from getting that infection, but you're also protecting that tiny baby on the train who's too young to get vaccinated.

Your grandma who's frail and immunocompromised, whoever, you're protecting literally everyone around you when you get vaccinated. So that's how vaccines work. They're pretty dang cool. Yeah, I love them. Big fan. Me too, major, if you can't tell already. So there are a lot of different types of vaccines.

And we're going to talk a little bit about the differences between them, not a full-on immunology lecture, but just a quick rundown. But I do want to say at the very top of this that all vaccines that are used are extremely safe. They're extensively tested and very highly regulated. And all the different types of vaccines that we have are very effective. And part of the reason that we have different types of vaccines is because different viruses and bacteria behave differently. And so we have to come up with different types of vaccines to target those specific pathogens.

So some vaccines, for example, the MMR vaccine, that's measles, mumps, and rebella, which you've talked about before, and also varicella, which is chickenpox. These are made from what we call live attenuated viruses. So that means the vaccine itself has a live virus in it, but that virus has been modified so that it's super, super weak. It's not a strong, virulent virus that actually makes you get sick. It's a weak little infantile virus. So this types of vaccine elicits a really good immune response because it's just like getting a real infection in that you have virus replicating in your body. But because it's such a weak virus, you don't get sick from it.

However, it does mean that some people who are immunocompromised, who have very weak immune systems, might not be able to get these live virus vaccines because their immune system might not be strong enough to fight off even a very weak virus. Gotcha. Okay. We also have whole killed vaccines. So these are vaccines that are a whole entire virus, so all of the different parts of the virus, but we kill the virus before we make the vaccine out of it. So that's the inactivated polio virus, the one that is an injection, or the influenza vaccine. And so are there also killed bacteria vaccines? There are, yeah.

So there's a killed bacteria vaccine for typhoid, and there's also a live vaccine for typhoid. Hey, there's both. Cool. So these whole killed vaccines, you still develop a really strong immune response, but you might need to get more boosters with this type of vaccine, because it might not be quite as strong of a response as you get from a live vaccine. But people who are immunocompromised can still get these killed virus vaccines because there's no live virus in these vaccines that's replicating. So going back to the flu vaccine, this means that you cannot get the flu from the flu vaccine. Correct. Absolutely not

ever. Nor can you pass on the flu to someone if you have gotten the flu shot. Exactly. It's not possible. It's a killed dead virus. Okay. Sometimes you might get a slight fever or muscle aches, especially in the arm that you got the shot in or the butt cheek where you got your vaccine. Do you know why, Aaron, that you might get a fever and feel achy? Is it some sort of innate immune response? Oh, you're so good. That's your actual immune system actually doing its job. So you might feel a little bit cruddy after you get a vaccine, but it's a lot less cruddy than you would feel if you got that actual infection. Right. And also you wouldn't die. You won't die. Like you could, like you might if you got the actual infection. Right. Exactly. Yeah. No, again, adverse events are extremely,

extremely rare for vaccines. They're very safe. The other thing about live virus vaccines, and the reason why some vaccines that we used to use as live virus vaccines, we no longer use live virus vaccines, is that there is a small chance that people can actually get sick, essentially, from the vaccine itself. Because it is a live virus, there is a chance that either the virus can change a little bit or mutate, or your immune system, even if you have a good immune system and you're not even compromised, might not just be strong enough to fight off that vaccine strain. So, for example, with the oral polio vaccine,

which is a live version of the polio vaccine, that isn't really used much around the world. It's only used in places where there is mostly, where there is still a chance of polio infection, like wild type polio still circulates. In about one in 2.5 million doses, is someone would end up getting polio from the polio vaccine. So it is theoretically possible that with a live virus vaccine that you could end up getting sick

or end up, for example, if you get the varicella vaccine and then end up getting a rash, you could potentially then pass veracella to somebody who's immunocompromised from that vaccine strain. Again, it's very, very, very rare. These would be considered adverse. events, and those are all reported to a system called the vaccine adverse events reporting system. And those would be detectable as vaccine strains, so the infection would be milder than if it were a wild type? Exactly, right. Yeah.

Okay. Okay. Okay. Okay. There's a few other kinds of vaccines. There are toxoid vaccines, which are very fun. Toxoid vaccines are an inactivated version of a bacterial toxin. So do you remember one that we covered already?

Diphtheria. Also, tetanus, okay. I think that toxoid vaccines are my favorite, and I don't know why. You know, actually, they're my second favorite. I'll tell you my favorite in just a second. Oh, I can't wait. So because some bacteria don't actually make you sick themselves, but they produce a toxin that makes you sick,

then we can just take that toxin and give you a vaccination with that inactivated toxin, which is called a toxoid. And that way, you're protected against any strains of that bacteria that contain the toxin. Very cool. Question. Answer. Colora produces a toxin. Is the cholera vaccine toxoid or is it? That's a good question. I'm pretty sure that it is. I was just looking at the cholera vaccine. I think I wrote it down. No, I have it right here. Hold on. Okay, so the one that was produced in 1996 was killed whole. And then the second one that was in 1991 is also killed whole cell. A wholesale vaccine.

And then the one in 2009 was also killed wholesale. Killed holes. So cholera is a killed wholesale vaccine. Maybe that's why it's not a super excellent vaccine. Yeah. It's not the most effective. Anyways. There are also what are called component vaccine.

vaccines. This is, as an example, the hepatitis B vaccine. So a component vaccine, instead of having an entire killed virus, it has just a small part, just the part that you would need to be able to quash that infection. In the case of hepatitis B, we have a single antigen, the surface antigen. So that's like what's on the surface of the hepatitis B virus, aka what your body needs to be able to see to prevent that virus from ever getting in to yourselves. So we have some vaccines like that that are just made of a single component of a virus. Okay. And are there also component bacterial vaccines? Yeah, there are for sure. But what's more common for bacterial vaccines are my favorite vaccine, the conjugate vaccine. So this is what is really commonly used against bacteria.

The reason is, okay, this is where we get back into some immunology. Oh, good. It turns out, bacteria are very good at evading our immune system. They're very clever. They've been with us for millions of years, so they know how to get around our immune responses. So a lot of bacteria on their surface have sugars, polysaccharides. These polysaccharides specifically evolved in order to evade our immune response because as it turns out, that whole amazing immune response that I told you about with the B-cell 10-gallon and the helper T-cells, those only work if the antigen is a protein. So what we figured out to outsmart these bacteria who have polysaccharges. polysaccharides, not proteins on their surface, is that we can take these polysaccharide sugars and we can

conjugate them, which means attach them to a protein antigen, for example, the tetanistoxoid, which we know is safe because we use it in vaccines, conjugate a bacterial polysaccharide to that protein and use that as a vaccine. And then our body will make antibodies to fight off that bacterial sugar. Oh. My brain is tingling. Isn't it? That feels so, that's so fascinating. I know. They're my favorite. So very cool. That's how we got vaccines for homophilous influenza, Nicerium and ingittitis, etc. So those are, I think, definitely the newest vaccines are conjugate vaccines. Well, even newer are DNA vaccines, which I'm not going to talk about today. But how fun, right? That's amazing. It's very cool.

How exactly are vaccines developed? Great question. I'm not going to answer it. Okay. But that's because we were fortunate enough to chat with Dr. Gail Rogers, who is a senior program officer at the Bill and Melinda Gates Foundation, which is the world's largest private charity foundation that focuses on improving health and reducing poverty around the world. and Dr. Rogers has worked on several vaccine initiatives at the development and deployment stages, and she shared with us her expertise on vaccine development. So I'm going to let her answer. Take it away, Gail. So Dr. Rogers, thank you so much for chatting with us today.

Oh, you're very welcome. I'm excited to do it. We're really excited to talk with you about vaccine development and the future of vaccine. So let's jump in. Great. Can you introduce yourself and tell us a bit about your background and your role now at the Gates Foundation? Sure. I'm a pediatric infectious disease physician and I worked in academic and a hospital or children's hospital for many years and then went into industry working on vaccines, specifically in the area of pneumonia. And from there, I moved on to work where I currently work at the Gates Foundation to also

in the pneumonia group to really both develop and make countries that are low resource countries have them have better access to vaccines, in particular to vaccines for pneumonia. Fantastic. So on this episode, we're trying to give listeners information about the process of vaccine development. So when we hear that a new vaccine has just been licensed, like the recent malaria or dengue vaccines, that vaccine has gone through rigorous development and clinical trials before it gets to the licensing stage. Could you explain the general process of vaccine development from when a vaccine is just someone's idea to when it's actually being distributed around the world? Sure. So it's a pretty lengthy process and that's something that, and I think the

right word is rigorous, as you mentioned. So it starts out in somebody's idea of doing this. And usually there is a preclinical stage, which is when it is looked at in the laboratory. It might be looked at against different strains of what you're trying to protect against. And then tested in some forms in animals, usually to start off with, before it goes into what's called First in Human Studies. And first in human studies are in adults, even though the vaccine may not ultimately be used in adults. it always to start off in the first phase in adults. And then moves once, and that really is for safety reasons. And then it goes into the second phase of testing to see if it would work against the target

as well as being safe in other populations. And that's where you start, and those are rather small studies, where you start looking at it in the populations that you want to target, being that for, in my case, it's babies, it's pediatric. So it would start off in adults and then move maybe to toddlers and then move to infants, where it is tested for safety and whether it is useful or whether it works. And then there is what is the big studies, which are called the Phase 3 studies, in which it's tested in many more children, in different schedules sometimes,

in different countries and really rigorously tested under many circumstances to make sure that they're safe. And then this is the one that you want to make sure that it works against the germ that you're treating, that you want, I'm sorry, that you're preventing. So after that, all the evidence is looked at, all this data is looked at by really committees in the countries that are made of committees of experts, of vaccine developers, of physicians, of safety experts, et cetera, where all the data is looked at. And based on those data, then licensure is given.

And from there, from when a license is given, then it can go and be used by doctors as well as by countries themselves. Excellent. So as we talk about on the episode, the past 100 years have been incredibly productive for vaccine development, especially the past 40 years, even the past 10 years. Yet there are still so many other pathogens for which there is no vaccine. So what makes a pathogen a good target or a more challenging target for vaccine development? Yeah, I guess it's really, it really is really interesting. Part of it is what you look to prevent. So a lot of the times one looks to prevent the worst of the worst, the deadliest. So certainly there is a focus on very serious, very serious pathogens being targeted.

And then what makes one more successful, others, I think, is the wide variety of the pathogens and how often they can change, which is pretty daunting. For example, I know you talk to Padmini, and she runs influenza, but influenza changes so frequently that the target for getting one vaccine to cope against all types is really challenging. I can tell you a specific case of the pneumococcus, which, you know, causes is the most common cause of pneumonia and common cause of death in children less than five, and for which there is a vaccine. And there had been a vaccine many years ago.

This is, you know, that was geared to adults. And it was only in when in the 90s, when the technology became available to know how to how to actually compose the vaccine to make children's immune system react to it, that a vaccine became available for children. So the challenges are in the pathogen itself, it's in how our immune system, you know, reacts to it, and what type of protection can be elicited at different ages. And then for pneumococcus, for example, there's over 90 serotypes, they're called, that cause pneumonia. And it's hard to envision trying to do this for all 90. So it started out with doing it for several, for seven initially. And when that worked, and those were the seven that were picked as being

the most commonly cause of disease, and then it got expanded. So currently we have 10 serotypes and 13, two different vaccines that target those serotypes, and more on the way as technology advances. Well, speaking of technology, so there is, as you mentioned, a lot of very interesting future avenues for vaccine development. So what do you see as some of the most exciting future prospects for vaccine technology? Where do you think we're going with vaccines? Oh, I think we are, you know, we're aiming to, you know, challenge and really try to control the worst of the pathogens as, as they become more, more prominent. So I think that for one, technology is helping us to try to get to a universal influenza vaccine, so old pathogens that we know of.

But what I'm kind of really interested in and not directly involved with the development, but really see as new diseases come up that are truly worldwide threats, such as Ebola, such as Zika, that it's pretty now clear that advances can be made pretty quickly in these field with the new technologies that will lead us to having vaccines, for example, for Ebola in a time span that was really unreachable or inconceivable before. So I guess I'm kind of hopeful for response time. In the future, I'm hoping for antimicrobial resistance, a vaccine for that, that would be multi-pathogen. I mean, this is really a dream. As organisms, they're pretty smart, and they can outdo antibiotics quite quickly.

I think that, you know, potentially going the, potentially going the vaccine route, is going to be important. That's really exciting. The idea of a vaccine for multiple pathogens that are anti-microbial resistant, I just, my mind just went, well, that's a dream. But you got a dream big. Right.

And, yeah, and, you know, just seeing, for example, there are other things as well that I think I can point to it. that are really interesting on a different realm, which is trying to get what we strive for at Gates, which is trying to get vaccines that are available or are in development to be aimed toward pathogens for countries that have lower limited resources, so developing countries, for example. And before we had vaccines that were really good, but we have no way. way that low-resourced countries could afford them. And now they're innovative financing mechanisms and, you know, involving tiered pricing, et cetera. So at the same time that they're licensed in the

U.S. in Europe and used in middle-income countries, they can be used in low-income countries as well. And that's, I mean, that's particularly exciting to have that kind of, um, equity being built throughout the world for prevention. Yeah, that's amazing. So for some of our listeners who want to dive even deeper into the future of vaccine development, can you help direct our listeners on where they can go to find more information about some of the vaccines that are being developed by the Gates Foundation and elsewhere? Yeah, sure. So I think that always a really good resource is the CDC.gov website.

they have a really of what's available as well as what's up and coming there's also the clinical trials.gov that tells you all the trials that are being done with vaccines as well as with other drugs so certainly so those are those are really good resources for you to look for that what's what's up and coming. Fantastic. Thank you so much. Well, Dr. Rogers, I think those are all the questions that we have for you today. Thank you so, so much for taking the time out of your busy schedule to chat with us today. We really appreciate it, and we had a great time.

No problem. This is great. Thank you so much. That was so awesome. We learned so much. Oh, my gosh, so much. How cool was it to talk with her? Amazing. Okay, so that's vaccines. Finally. Yay.

That's all I have for the biology. It's like a whole immunology course. Yeah. I feel armed with knowledge. Great. Well, arm me with some leverage then. Okay, well, get ready to learn. I can't wait.

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That's Q-U-I-N-C-E dot com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. For this episode, I'm going to give an overview of the history of vaccine development and the observed effects in disease prevalence after vaccines were widely adopted. I'm not going to go heavily into the various anti-vaccine. movements yet. I'm saving that for next episode, so hold on. Hold tight. Hold on to your butts. Hold on to your bets. And I'm also not going to go into the details of every single vaccine that has been created because if I were to do that, we would be here forever. But I am going to

touch on the highlights of vaccine developments and what I see is the biggest stages of vaccine history. So, act one. I love it. Blossom. Yep. As we know, the word vaccine itself tells us its roots. Edward Jenner developed and tested the first vaccine against smallpox in 1796 in England from a cowpox sore. Vaca means cow. Even though cowpox is no longer used in the smallpox vaccine or any vaccines, the name stuck and is used for all diseases. Okay, so that much we know. technically speaking, though, the smallpox vaccine really is the first vaccine, but that's not exactly where the history of vaccines begins.

Some of this is a bit of a refresher from past episodes, by the way. So the history of vaccine starts over a thousand years ago in China, where writings tell of a tradition called inoculation used to prevent smallpox infections. This practice may even go back to as early as 200 BCE. Wow. Yeah, it's amazing. It's totally amazing. Basically, you were supposed to grind up scabs from people who had recovered from a mild form of the disease and then blow them into the noses of healthy children. Gross.

So gross. This would usually result in some mild symptoms, but it would also ensure that the child would not come down with severe smallpox later in life. Side note. The earliest immunization might be even older than variolation against smallpox. So apparently, people used to try to prevent severe or disfutable. figuring Leschmeniasis infections by scraping an active lesion of someone with the disease and putting it on a child's arm or butt. Really?

Yeah. I know. And so there isn't a licensed Leshamianysis vaccine today, but people at the Texas Children's Hospital Center for Vaccine Development are working on it. Okay. Spoilers. Back to, yeah. Back to variolation slash inoculation.

Because the Silk Road allowed for exchange, not just of goods, but also ideas, Turkey picked up this practice as well. So this concept was starting to pick up steam in Eastern Europe around the same time that people were starting to travel to the new world, bringing with them smallpox among other killer microbes like measles and influenza that would wipe out the majority of the native populations. Yep. In Turkey, the practice was refined a bit.

So instead of snorting ground-up scabs. Snority. Just like do a line of ground-up scats. So, gross. So people actually injected the infectious material just under the skin. So this was variolation. And so even though smallpox was a deadly killer that could devastate communities, people outside of Turkey and China were super hesitant to take up the practice because they viewed it as dirty,

despite numerous reports of its efficacy. This is also the same people who would just, dump poop right in the streets, but cool. That's fine. Cool. A few people went against this thinking, and I mentioned some of them on the smallpox episode, such as Lady Mary Montague and Cotton Mather. And it's not surprising that variolation was slow to catch on, really, because stories of

its effectiveness were largely just stories. At that point, clinical trials weren't yet a thing. But these iconoclastic thinkers definitely helped pave the way for the acceptance of variolation and eventually vaccination. Okay. Smallpox vaccination, as we all know, was developed by Edward Jenner in 1796 in the story we all know and love. Jenner, who already knew about variolation, had his revelation

when he realized that milkmaids never got smallpox because they were protected against it after being exposed to cowpox. Blah, blah. Blah. Blah. See episode three. Yep. He tested this out, and I do want to include this part.

He tested this out on a child named James Phipps. Little Jimmy Jim. Inoculating him first with cowpox on May 14th, 1796. That's the day this episode's being released. Yes. Oh, my God. Did we do it on purpose? 100% no.

No, definitely not. This is my favorite. Just serendipity. I love it. 223 years ago today on the day that hopefully, Hopefully a lot of you are hearing this is the day of the first vaccine. Oh, my gracious. Oh, I feel so excited in my heart.

Good, good. Okay, so anyway, we got Phipps with this cowpox injection thing. He's protected from smallpox. The Royal Society of London is like, okay, this looks great. I love it. Okay. So I don't remember if I mentioned this in the episode of Smallpox, But apparently the cow that was the source of the cowpox used in this vaccination was named Blossom.

Hence the title of Act 1. So her hide, Blossom's Hide, is displayed at St. George's Hospital in London. So if there are any London listeners that are out there, please send us a pick. Okay. Was Jenner actually the first to come up with this idea of cowpox preventing smallpox? Probably not. We know of at least one of the person who, 20 years before Jenner's vaccine, amidst a smallpox outbreak, decided to infect his family with cowpox, and no one became infected. But word got around and the community was like very angry and anxious.

They were like, this family is going to grow horns and utters and they're going to mutate. So you all need to get out of here. So the family moved to avoid the constant physical and verbal harassment from their wonderful neighbors. and they lived out along in smallpox-free life. Alone forever. Alone. So it seems not so much that Jenner was the first to make the logical leap about cowpox protecting against smallpox, but rather the first to conduct trials on multiple people and bring his results to the attention of a large and legit medical society.

And this first vaccine would light the way for the development of so many more. Act 2. Chance favors the prepared mind. Even though vaccination, God, I'm such a dork. I love it. Even though vaccination clearly saved lives by preventing severe cases of smallpox and decreasing epidemics, people didn't really know exactly how it worked. For about 60 or 70 years after Jenner first vaccinated Phipps, germ theory, which is the idea

that microorganisms can cause disease and can be transmitted. from person to person, it hadn't really been developed, much less widely accepted. Luckily for the world, Louis Pasteur had had it up to here with sour wine and spoiled beer. Haven't we all? I'm kidding, though, about that, probably. I don't know for sure if that's what motivated him. In the 1850s and 1860s, Pesture, who's one of our favorite microbiologists, was investigating fermentation in alcohol, specifically wine and beer, and found that yeast, a microorganism,

was responsible for the production of alcohol, and that when exposed to certain other microorganisms, the wine or beer could spoil. He made the logical jump from microbes spoiling wine to microbes causing disease and humans and animals and switched his research focus from alcohol production to the field that we now call microbiology. Where do vaccines come into this? Okay. In the summer of 1880, So almost 100 years after Jenner's vaccine, Louis Pasteur was going on vacation. He packed his bags, double-checked the stove was turned off, and told his assistant to finish up a chicken cholera study they had been working on. So chicken or avian cholera is caused by pasturella Molocita or something like that, for those of you who might be curious. Apparently it's extremely high mortality rate.

In the chickens? And yeah, and wild and domestic foul. Oh, poor babies. So Pesture just set off for holiday, leaving his research in good hands. Or so he thought. It turns out the assistant was busy getting ready for his own vacation and completely forgot about the experiment. Luckily, he returned before Boss Pesture did, and when he got back, he saw the test tube with

avian color broth still sitting on the bench. and the chickens were running around blissfully unaware that they had narrowly escaped a horrible death. The assistant was like, well, better late than never, and injected the chickens with the stale broth. Nothing happened to the chickens. Oh, my gosh. Right. I didn't know this little story. This is so cool.

Isn't it fun? Yeah. So he tried again with a fresh batch of avian cholera. Again, nothing. At this point, the assistant, Chamberlain, is like, oh, God, he's in full panic mode. He's like, I am going to, he's like, I'm about to get fired, but I have to tell the boss. So he fills in Pesture on the results.

And Pesture is like, oh my gosh, are you kidding me? This is the most exciting thing. What do you mean? Do the same exact experiment. Leave the broth out for a long time. And then just do the whole thing all over again. I love this. I feel like I would love to work for Pester.

You're like, okay, I got to tell my boss I really screwed up. And they're like, this is the best news. He's like, what genius. So then that's what Chamberlain does. And again, the chickens remain healthy and cholera-free. Oh, my gosh. Both Pesture and his assistant realized that their stale cholera was acting to protect the chickens from disease in a similar way as to how the smallpox vaccine worked. But even cooler, unlike that smallpox vaccine, this avian cholera vaccine, this avian cholera

vaccine was made from the same species of bacteria themselves. So you didn't have to find a mild or strain or species to create a vaccine like the cowpox virus and the smallpox virus. You just had to weaken the existing one. And so this opened this door in pasture's mind. Hence the phrase commonly attributed to him, chance favors the prepared mind. But he began to test various ways, such as chemicals, to weaken or attenuate different bacterial species to make more vaccines. This itself was a contentious issue because many scientists believed that bacteria were static. They were either virulent or not, and they didn't change over their lifetime. According to them, adding chemicals to weaken the bacteria was not possible.

But Pesture's avian collar vaccine was not a fluke. In the summer of 1881, Pestor successfully produced an anthrax vaccine by attenuating the bacteria using fennel. He demonstrated the effectiveness of his vaccine on various farm animals, and it was pretty widely accepted, especially by farmers, because anthrax was a huge killer of cows and sheep and goats and so on. Pester decided to keep the name vaccine as a nod to Jenner, and the story of vaccines was about to enter its heyday. Act 3. Low-hanging fruit. Pastures' development of the avian cholera and anthrax vaccines using chemical inactivation marks a pretty

big turning point in the history of vaccines. There was now a template or a roadmap that scientists could follow to try to develop vaccines against other diseases. First, identify the causative agent, then weaken it using chemicals or through multiple passages, try it out on animals, and then try it out on humans if things look good. In 1885, Pesture developed the rabies vaccine, which I talked about in the rabies episode, and then Almoroth Wright, Richard Pfeiffer, and Wilhelm Cole developed the first typhoid vaccine in 1896. That same year, Waldemar Mordecai Halfkind developed a cholera vaccine. Yeah, what a name, which he promptly tested on himself and then narrowly escaped with his life.

Oh, apparently. Yeah. But he decided. effective vaccine there? Well, he thought good enough. So he tested that out on a bunch of friends. And fortunately, it worked. And then he went big time with trials in India. So while he was in India, testing at his cholera vaccine, Halfkind witnessed the third plague pandemic and the death and chaos that it brought. He was tasked with developing a plague vaccine, which he did in 1897, and which he, in typical fashion, tested on himself first.

He experienced a mild fever but survived and figured it was good enough to test on other people, such as prisoners. Naturally. Fortunately, the vaccine did work without serious side effects, and his quick work probably saved thousands of lives. However, his fame and accolades were short-lived. In 1902, after being given the plague vaccine, a bunch of people developed tetanus symptoms and 19 died. died. Oh. Yeah. So the deaths were traced to a bottle of plague vaccine manufactured by half kind. And he was fired and exiled and remained unemployed for at least four years. And this whole time he was begging to read the entire report of the inquest. Like what exactly

happened? How could this have gone wrong? I don't understand. So he finally got his wish. And as he read it, he learned that the specific bottle had been handled by a lab tech who dropped his foreseps in the dirt. and didn't bother to clean them or get a replacement. Tetanus loves soil. That's where it hangs out, man. Yeah. Oh, that's so awful. Right.

Yeah. Sterell technique, important. Very. So eventually, Halfkind was publicly exonerated, but the damage to his reputation was already done and would never fully recover. Halfkind's contaminated plague vaccine is a perfect illustration of the lack of overrequent, oversight on vaccine development during this time. While all of these vaccines and antitoxins were being produced in the late 1800s, there wasn't really any government regulation. So a classic example

of technology outpacing the law. And as you might expect, things took a tragic turn, or rather they took several tragic turns. Around 1901, the year before the Half-Kine incident, some smallpox vaccines and diphtheria antitoxin were contaminated with tetanus, and 24 people died. Following these tragedies, people were like, we demand that the government look over the manufacturing of vaccines. And they got their wish. So right after this, in 1902, Teddy Roosevelt signed into law the Biologics Control Act, which would require that health commissioners oversaw vaccine production,

which is some much-needed legislation. Vaccine development didn't slow down with these new regulations. If anything, it spurred researchers to create safer, more potent, more stable vaccines. And there were still plenty of devastating. devastating diseases for which there was no effective treatment or protection. In the 1920s, researchers started to experiment with adjuvants, which comes from the Latin four to help, adding them to increase the efficacy of a vaccine by eliciting a stronger immune response that lasted longer and provided better protection. The French scientist Gaston-Ramon

discovered that the chemical formalin, which had been used just to preserve antitoxin, also actually inactivated the toxins. So this allowed him to develop the diphtheria vaccine in 1923, as well as a tetanus vaccine a few years later. Gosh, it seems like they need it since all their vaccines keep getting infected with tetanus. Right. His contributions to vaccine development have resulted in over 60 million lives saved, estimated. Wow. Jeez. Next was pertussis, Pertussus, aka Whoop and Coff was an infamous child killer alongside measles, still is, and it will definitely have an episode all of its own eventually. Yeah.

And because it was so feared and killed so many children so horribly, it was high on the list for vaccine development. But it was a tough nut to crack. First of all, it had been a real struggle getting the bacteria isolated. And even once it was isolated, it was nearly impossible to culture. but eventually a broth was developed, which allowed Pearl Kendrick, Grace Elderling, and Loney Clinton, Gordon to develop, test, and implement a pertussis vaccine in 1940 that would be used up until the 1990s. Wow. Which is pretty dope.

Yeah. Go ladies. During the 1930s, vaccines against influenza tuberculosis, the BCG vaccine, and yellow fever were developed with Max Tylerer, earning the only Nobel Prize to be given just for the disqualification. of a new vaccine, the yellow fever vaccine. Okay. It wasn't always sunshine and rainbows in the vaccine world. There were some dark turns, including the unethical experimentation on human volunteers that was rampant throughout this entire period.

Quote unquote volunteers? Right. Yeah. Sorry. I forgot to include the air quotes. The contamination of a batch of yellow fever vaccine that led to 50,000 military personnel getting infected with hepatitis B. during World War II.

Holy cred. Yeah, yeah. This is when they didn't know that hepatitis B can survive in plasma. And also the cutter polio vaccine incident in which a batch of polio vaccines were contaminated with the live virus resulting in the paralysis of 56 people, mostly children.

So I'll talk about this a bit in the polio episode. But for each of these, either new laws or regulations were put into place to prevent additional suffering. Most of the vaccines that I've mentioned so far could almost be looked at as kind of the low-hanging fruit of the microbiology world. Of course, it was a huge leap of technology and scientific thought to develop the concept of vaccines in the first place, but once it was there, scientists applied it to the most common diseases, and in particular those whose causative agent

had been identified, those that were cultureable, responded well to attenuation, and had low mutation rates or strain diversity, because these were diseases that were fairly straightforward to develop vaccines for. Right. It was almost just a race to see who could publish their vaccine first in many ways. It's pretty cool. By the 1950s, even though there was a smallpox vaccine, a rabies vaccine, a diphtheria vaccine, yellow fever vaccine, and several others, many terrible diseases including measles, mumps, rebella,

hepatitis, meningitis, hemophilus influenza type B, and polio still killed or permanently disabled many, many people, children in particular. Act 4. Cultured. Why did vaccine development for diseases like measles, rebella, and polio lag behind that of diphtheria plague and cholera? Tell me. An important part of that answer is the fact that measles, rubella, and polio are caused by viruses that can only replicate in cells, while diphtheria, plague, and cholera are caused by bacteria that can replicate on their own, which makes them much easier to grow in a lab setting, because all you need is a correct nutrient broth. If you wanted to make a lot of bacteria to produce your vaccine or study the bacterium, you would just make a lot of broth.

On the other hand, viruses need cells in order to reproduce. So if you wanted a lot of viruses, you had to have a lot of cells where they could grow. And that's trickier than it sounds. Where do you get the cells? Well, one solution was to maintain large numbers of lab animals to infect with the virus. Not great. Another was cell culture. Cell culture, which we haven't talked that much about so far,

involves isolating cells from living tissue and growing them under controlled settings in a lab. These cells can come from animals or humans or plants, but we're not going to talk about those. Sorry, Matt. And they often can continue to replicate indefinitely. All you have to do is just take a little subset of the cells, place them in a new sterile container with the appropriate nutrients, and keep them at a temperature they like. Cell culture is an amazing technology that was really only getting at start in the mid-1900s, but a huge, developments were occurring as researchers kept finding new applications for the cells. One of these applications was growing large quantities of viruses to study and to try to develop

vaccines for. Before cell culture, vaccines for viruses were made either directly in animal tissue, such as chicken embryos, in the case of yellow fever, or animal nervous tissue, such as in the case of rabies. But those were not perfect solutions by any means. Regulating the growth of viruses was more difficult in both cases, and maintaining large numbers of lab animals was expensive and logistically challenging. Cell culture went a long way towards solving these problems. The history of cell culture is fascinating, particularly with the ethical discussions, but I just can't go into it here. But we are going to cover it someday, so keep an ear out for a Henrietta Lacks episode. Oh, definitely. Okay. So cell lines began to be used to culture

viruses which greatly advanced the field. One of the most important developments involves our buddy John Enders, who was of Enders fame, who was one of the creators of the measles vaccine. Also, I just love his origin story. Okay. While finishing his master's thesis on Middle English at Harvard. What? So he got a master's in Middle English.

Give me a break. He was all set to do a PhD. on Middle English. Middle English. But he found himself, yeah, he found himself rooming with an Australian bacteriologist. They became close buds. He was so charming. And Anders would tag along with him to the lab.

And he was like, whoa, what is this? This is super cool. What are you doing? I love this. And so he decided to get his doctorate in microbiology instead of Middle English. That's everyone who studies Middle English who listens to this podcast, right? And then emails us like, no, I'm doing epidemiology. And we're like, yes.

By the way, those emails literally break our hearts with happiness. They're the most thrilling. Oh, yeah, absolutely. Okay. So in the 1940s, Enders began to doubt the conventional wisdom that polio virus only grew a nervous tissue, and he decided to try to grow the virus on other types of human fetal tissue, which was successful. So this was a huge turning point in polio research that would lead to the

the creation of the vaccine that saved countless lives and prevented so many cases of paralysis. This development also earned Anders and his two research partners, Weller and Robbins, the Nobel Prize in Physiology or Medicine in 1954. Using a similar technique, but monkey kidney cells rather than human fetal cells, Jonas Salk developed the polio vaccine in 1952. Monkey kidney cells had been used for a while to grow and study virus. but something concerning came to light in the 1950s. Many of these cells, which were still being used by people like Albert Sabin and Hillary Kaprovsky to develop live polio vaccines, were found to be contaminated by a virus called

SV40, SV meaning simian virus. 40, just being random. The 40th one or something, maybe? Yeah, I think so. So whether these viruses caused any kind of disease in humans wasn't known, But this was really worrisome because many animal cell lines had been found to be contaminated with cancer-causing viruses. The live polio vaccines developed by Kuprovsky and Sabin, which had been widely tested but not yet licensed, were found to be contaminated with the virus. And Salks killed polio vaccine, which had been administered to millions of people around the world, was also found to contain viral particles of SV40.

Wow. So in those people who had already received the live vaccine, researchers found no antibodies for SV40, which indicate that it didn't cause any major infection, but that's still a lot of unknowns. Yeah. And so after this initial study that notified researchers of the presence of SV40, a researcher named Bernice Eddy had been on the hunt for any hidden dangers of the viruses tucked away in these vaccines, and she found some disturbing things. When injected into lab animals such as hamsters, the animals developed tumors and died within a few months.

Not great. No. She published her work, which contributed to the general controversy and concern that was being raised about the existing Salk and Sabin polio vaccines. And she was promptly demoted by her boss, who told her that she wouldn't be allowed to speak at any more meetings without him reviewing and approving everything she was going to say. Rude. Ugh, gross. By that time that regulations were put into place to prevent the contamination of the polio vaccine by SV40, by the time people were like, okay, this is actually a big deal.

Over 98 million Americans had received the Salk vaccine, which had at least inactive and very possibly active SV40 particles in it. Okay, so another researcher who tried to sound the alarm bell about Sv40 was Maurice Hillman, who would go on to become the most. most prolific vaccine developer ever, ever, surpassing even John Anders. His name should be a household name, but he was just super modest. He and his team developed vaccines for over 40 diseases, over 40 vaccines. What? His work is estimated to save 8 million lives every year. Isn't that amazing? That is amazing. Yeah. I really wanted to shout him out. Okay. So anyway,

Vaccines made from SV40 infected cells could not be considered safe, which meant massive inexpensive testing, as well as throwing away the vaccines already produced. There needed to be a longer-term, more stable solution. Enter a man named Leonard Hayflick. Hayflick worked on cell culture at the Y-Star Institute in Philadelphia, Pennsylvania, under Hillary Kaprowski. He had developed a strain of cells from human fetal lung tissue that he believed held great promise for the field of virology and for the development of vaccines overall. This cell strain, which he called W.I.38, came from a fetus that had been aborted by a woman in Sweden in 1962, where abortion had been legal since 1938.

I also want to point out here that tissue from aborted fetuses had been used in scientific research for a while at that point, quite a long while, and is still widely used today, with many more legal regulations in place regarding consent. Just FYI. Yeah. Hayflick wanted to cultivate these lung cells because he believed they would be cleaner and safer for vaccine production compared to monkey kidney cells. The W.I.38 cells did not turn cancerous, as did many other cell types used in culture, and they were shown to be free of any viruses. So most importantly, though, Hayflick was able to grow human viruses in these cells, and that had powerful implications for vaccine development. Because if you can culture, you can study, and you can most likely attenuate.

So these cells were shown to be stable, diploid, non-cancer-causing, and could be maintained in a lab for months. It was a huge deal. But the medical community wasn't quite ready to embrace W.I.38 cells. Many who had spent years developing vaccines using monkey kidney cells, like Albert Sabin, weren't ready to trash their research program and started new, despite the promise the W.I.38 cells had. Others expressed caution. These cells were new. Time would perhaps tell whether they were safe, but not enough time had passed yet. So W.I.38 cells, particularly in the U.S., took a backseat in vaccine development compared to monkey kidney cells. Not everyone, though, was willing to give up on them.

Stanley Plotkin, a vaccine developer, worked at the Y-Star Institute along with Hayflick and Kuprovsky. These are some great names, by the way. I know, right? He had witnessed the rising concern about viruses contaminating monkey kidney cells and became convinced that Hayflick's W.I.38 cells were the way to go.

A couple years after Hayflick had published on these cells, a devastating Rubella epidemic in the U.S. resulted in 12.5 million infections. What? One in 15 Americans. Holy B. Gwak. 2,100 people developed encephalitis.

6,250 pregnancies ended in miscarriage or stillbirth. 5,000 women chose to get abortions because they had been infected during pregnancy. Congenital rebella is terrible. Yep. 2,100 infants died soon after birth and 20,000 babies were born and survived with congenital rebella syndrome. 20,000. Oh, my uterus. So these numbers are actually probably an underestimate

because physicians weren't required to report rebella cases until a year after this epidemic. So this epidemic was horrible, and the urgency for an effective vaccine was keenly felt. Plotkin, who had been working on a rebella vaccine using W.I.38 cells, decided to test his out. To be blunt, it wasn't great. Didn't work.

Many toddlers in the experiment straight up developed Rebella, while others developed no protection whatsoever. Oh, dear. Yeah. But Plotkin didn't give up on his vaccine. Instead, he tried different ways to weaken the virus, growing it over and over again, or growing the virus at different temperatures.

Eventually, he hit the sweet spot. Multiple passages and a low incubation temperature of 86 degrees Fahrenheit or 30 degrees Celsius, weakened the injected rebella enough to not cause any disease or side effects, but left it strong enough to produce antibodies and lasting immunity. Despite Plotkin's W.I.38 derived rubella vaccine having super solid experimental results, it was not getting any traction. Instead, it was getting overshadowed by a different rubella vaccine developed in monkey cells. When Plotkin's W.I.38-based vaccine was dropped from production in 1970, it wasn't noticed by too many people beyond those involved in its development.

But there was another person who did take notice because she had serious concerns about the efficacy of the animal cell-based vaccines that had been selected over the W.I. 381. Her name was Dorothy Horstman, and she was a pediatrician and vaccinologist at Yale Medical School. she found that 80% of those who received the commercially available Rubela vaccine became reinfected within a few months. Really bad. Not effective. That's a lot. And even more concerning, they didn't necessarily develop overt signs of the disease,

but were silently infected, meaning they could shed the virus to pregnant women who were unvaccinated. So she turned to Plotkin's vaccine, testing it along with the commercially available ones at daycares. And she found that Plotkin's vaccine, in contrast to the two commercially available ones, produced an immune response and the types of antibodies that mimicked natural infection, making the immune memory last much longer. So there was a clear winner in this race.

Following Horstman's research, Plotkin's W.I.38-Rubella vaccine was finally licensed in 1978 and the only other competitor, a vaccine made from animal cells, was withdrawn the following year. Wow. W.I.38 cells have gone on to make vaccines that have been given to over 300 million people, and similar methods were used to make an additional 6 billion vaccines. Whoa. These vaccines have saved millions of people from horrific deaths or excruciating infections or debilitating disabilities from infections like rebella, rabies, chickenpox, measles, polio, hepatitis A, shingles, and adenavirus. They've been so integral to the development of vaccines to laying the groundwork for our understanding of how cells function and for examining the safety and application of potential pharmaceuticals that they are displayed in little glass tubes at the National Museum of American History in D.C.

Yeah. Oh, I was just there, and I didn't know those were there. I would have sought them out. Just went straight to Julia Child's kitchen. Oh, of course. Those high counters, got to love them. These cells, which have their origin in a single aborted fetus, have prevented millions and millions of miscarriages, infant deaths, and pain and suffering around the world. There's so much more to the story of W.I.38 cells, if you can.

can believe it. And if you want to learn more, I recommend the book The Vaccine Race. The wise-bred success of various vaccination programs led to record lows in diseases that previously killed or disabled millions each year. Arguably, the biggest accomplishment in vaccine history, besides the invention of vaccines themselves, happened when the world was officially declared smallpox free in 1980, with the last known wild case occurring in 1977 in Somalia. The effort to eradicate smallpox left a larger legacy than just eliminating the disease, though. So by assembling this global team to target this disease, it had built a vaccine infrastructure that could be used to deliver vaccines all over the world.

So the WHO used this already existing infrastructure to deploy additional vaccines, which I'm sure we'll hear more about. And the WHO also set up the expanded program on immunization. EPA to do this. Throughout the 70s, 80s, 90s, and 2000s and beyond, more vaccines were developed, including ones for chickenpox, strepneumonia, Nicerianinotidus, hepatitis B, hemophilinthalinthi type B, cue fever, hepatitis A, rotavirus, typhoid, human papillomavirus. I mean, just, it's amazing. Tick-born encephalitis, got to throw that in there. Yeah. I wanted to illustrate just how many lives vaccines have saved and improved since being developed. So this is what I'll call vaccines

by the numbers. Yes. And this just compares U.S. numbers, because that's all I could find in a table format. So if anyone has global comparisons between the pre-vaccination era and the post-vaccination era, please send them our way. Diphtheria. Before vaccines, annually, 21,000 cases, 1,800 deaths. In the 21st century annually, zero cases, zero deaths. Measles. In the U.S., before vaccines annually, 530,000 cases. Jesus. 440 deaths.

21st century TBD. But let's just say for now tentatively, over 100 cases annually. Yeah, average. Pertesis annually, before vaccine. 20,000 cases, 4,000 deaths, 21st century, on average, 15,600 cases annually, 27 deaths. A lot higher than I thought, actually. It's a lot of waning immunity with the pertussis vaccine. Yeah.

Paralytic polio, before vaccines, annually 16,300 cases, 1900 deaths. 21st century zero, zero. Wow. Rubela, in 1969, which is the last year before a rebella vaccine was licensed, there were over 55,500 cases reported to the CDC. And 10 years later, that number was 11,800. So between those years, the number of congenital rebella cases in the U.S. declined by 36%.

but at the turn of the 21st century, there were 176 reported cases of rebella and nine cases of congenital rebella. Wow. Isn that amazing? That is absolutely incredible. In 2005, the CDC announced that endemic rebella had been eliminated from the U.S. And 10 years later, in April 2015, Pahoe, the Pan American Health Organization, announced that endemic rubella had been eliminated from the Western Hemisphere. I just got chills.

too. And it's hot in this room. Smallpox. There are so many of these. Smallpox in the first half of the 20th century, 29,000 cases and 337 deaths annually. Zero, obviously, in the 21st century. Yeah. It's gone. It's gone. Tetanus in the first half of the 21st century, 580 cases and 470.7,000. two deaths annually. Wow. 21st century, 41 cases, four deaths.

Before the vaccine, homophilus influenza type B caused meningitis, bloodstream infections, and pneumonia, and 20,000 children every year, killing 1,000 of them and causing permanent brain damage

and many more. When fear drove down vaccination rates, outbreaks happened in 2008 and 2009 in Minnesota, Pennsylvania, New York, Oklahoma, and Maine, with at least four children dying because those parents chose not to vaccinate them.

Um, okay. Chickenpox. The incidence of chickenpox and shingles as well as U.S. hospitalizations and deaths, because people do die from chickenpox and shingles. Yes, they do. It declined by 90% after it became part of the routine schedule. Wow. And when a booster was added, the incidence of the incident.

fell another 81%. Wow. No one younger than 20 years old has died of chicken pox in the U.S. since 2010. Wow. Yeah. That's amazing. Okay. Two more numbers. It is estimated that the work done by John Enders and his teams, Ender's fame, has saved over 120 million lives as of 2017. And I said it before, but I want to say it again, Maurice Hilliman's work is estimated to save 8 million lives each year. So he has saved more lives than any other scientist. So let's hear it for Maurice. I kind of want that to be the title of our episode. Let's hear it for Maurice. I like it. Yeah. Okay, good. I really like it. The need for vaccines, has never diminished, and the recent resurgence in vaccine-preventable illnesses only highlight

their importance. Erin, I'm hoping you'll tell me some good news about vaccines today. All right. After one more short break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a constant. It's a constant. concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who watch.

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Lately, car buying has become a pretty dull experience, but on eBay, behind every car in part is a story waiting to be shared. There was a guy who bought a 2020 Porsche Cayman GT4 on eBay. It was well loved. There are plenty of Cayman's in great condition on eBay, but this one needed some work. That's just the start of the story. So after this guy gets a great deal on his dream car, he rebuilds the whole thing with all these parts he found on eBay. Performance brakes, suspension, body panels, the works, guaranteed to fit. Next thing you know, this nearly scrapped Cayman was out there on the track as a full-blown race car.

You're ready to go daily driver, your next restamod. Hello, Lotus Alon, hand the parts to finish it. eBay has thousands of cars and is the largest online selection of vehicle parts and accessories. eBay. Things people love. All right. So let's talk about some of the vaccines, what the vaccine recommendations are around the world. Okay. Great. So the World Health Organization has a list of recommended routine vaccinations. So I'll kind of just go through this. You've already mentioned a lot of these because, as it turns out, these recommended vaccinations are in general the ones that have had the biggest impact around the world

in terms of decreasing the number of disease outbreaks that we see. So the World Health Organization recommends as a blanket statement for all countries with vaccination, programs that they include BCG, which is the tuberculosis vaccine, which I think is interesting because that's one that the U.S. does not vaccinate for. But that one, the World Health Organization recommends as a general recommendation. Why doesn't the U.S. vaccinate against that? So the BCG vaccine is a vaccine for tuberculosis that's good at preventing disseminated, so like full-body tuberculosis in infants. For some of the vaccine. some reason that's not entirely clear, it's not great at protecting adults. So it doesn't

protect adults from getting TB. Yeah, it's not good in adults. It's just good in kids. And it's really just good against disseminated infection. And so infants in a lot of countries get BCG, like at birth. But in the U.S., we don't have high enough rates of tuberculosis to justify giving the BCG vaccine, essentially. Interesting. Yeah. And then some countries only give it to certain subsets of their population if they have, if those children happen to be at high risk or something like that.

Okay. So, all right. We've also got hepatitis B, which is another vaccine giving to infants at birth. Polio, DTP, which is diphtheria, tetanus, and pertussis. H.I.B. Homophluous influenza type B, the horrible one that causes meningitis. the pneumococcal vaccine, which there's actually a couple different pneumoccal vaccines, but this protects against meningitis as well as pneumonia.

Okay. In children and adults, so there's different ones for children and adults. Rhodivirus, measles, rubella, and HPV. So these are the ones that WHO says, every country should vaccinate for sure for these at a minimum. There's a few more that we vaccinate for in the U.S. that the World Health Organization has on their list as recommending for countries that have strong vaccination programs where they can generally achieve at least 80% vaccination coverage.

And so those are mumps, varicella, which is chickenpox, and seasonal influenza. Great. So that's the U.S. vaccine list. We actually also vaccinate against Niceria meningitis in the U.S., which is truly, truly, horrible illness that causes meningitis. And that one is recommended by the WHO for some countries. So the U.S. is one of the countries that has that on their recommendations list. And then there's a whole number of other vaccines that are recommended in certain geographic areas or for certain populations. So for example, some countries like China have Japanese encephalitis as a recommended vaccine for all

children. Hepatitis A is recommended a lot for travelers. It's probably going to be put on the routine vaccination list here in the U.S. pretty soon. And then there's things like typhoid, cholera, yellow fever, tick-borne encephalitis. Okay. I'm getting that this week. Yeah, it's thrilling. So, yeah, so basically recommendations differ around the world because every country is going to decide what is the most important diseases that they want to vaccinate their people

against. And different geographic regions are going to have different risk profiles. so they're going to vaccinate against different diseases. But something that's really important to keep in mind about all of these recommendations is that vaccines are always recommended to be given to the youngest age group that's at risk for developing that disease. So that's a very important part, is that we always want to vaccinate before someone has a risk of being exposed to that pathogen.

Right. And in populations whose members we know are going to respond to that immunization. So some vaccines we don't give to infants, for example, because they might have maternal antibodies still circulating that would neutralize that vaccination. So we have to wait to give some vaccines to infants until they're a little bit older. But in general, we give vaccines to people before they're ever. exposed because a vaccine doesn't do you any good if you've already been exposed to the pathogen. Yeah. Makes sense. What about rabies? Oh, so rabies is a, yeah, rabies is an interesting one.

We give that after because in that case, it actually does help protect you after because when the rabies virus is in, once it makes it into your central nervous system, your body can't produce antibodies against it. So by giving you a vaccine that circulates for longer in your bloodstream, you have time to actually create those antibodies against it. Right. So in the case of rabies, it does work to immunize after. Okay. But for most other pathogens, it doesn't. Okay. So how does coverage actually differ across the globe when we look at all these different vaccines? Yeah. Honestly, it differs so much that it's hard to even get a handle on it. Right. Right. The World Health Organization has numbers ranging from 50% of all children have gotten the polio vaccine

who should have gotten the polio vaccine like in 2018. 85% of children have gotten MMR and DTP and things like that. But the thing is that those numbers don't really tell us much because geographic variation is so high that in some countries you're going to have over 99% coverage and in some countries you're going to have extremely low coverage. Right. And so even, for example, in the United States, so the way that the U.S. mandates vaccinations is that children have to be vaccinated by the time they enter public school.

So by the time you're in kindergarten, if you're going to a public school, you have to be vaccinated. But every state handles differently how they enforce that mandatory vaccination. So some states make it easier to get exemptions, whether for, medical or religious or personal reasons, you can request exemptions. And some states make it really, really difficult where you basically can only get an exemption from vaccines if you have a very legitimate medical reason, like a serious allergy or immunocompromise or something like that. Right. And there are just like two states that don't allow religious or philosophical exemptions? I can guess what one of them is, although I didn't look up which states they were. But,

So in 2017-2018, in 49 states that reported their vaccine coverage rates for kindergartners, while you look at the U.S. overall, vaccination rates were very high for things like DTP and MMR and Veracella, anything from usually about 95 percent if you look at the whole United States. In Washington, D.C., which had the lowest coverage, it was only 81%. And in Mississippi, 99% coverage of kindergartners. Okay. Interesting. Does Mississippi have philosophical exemptions? No, they do not.

You cannot get exemptions for religious, philosophical, or conscientious reasons in Mississippi. Only medical exemptions. Yeah, I didn't know that. Fascinating. That's a high five Mississippi. Right? Way to go. So you can see that even within the U.S., which is a very small part of the world, we have huge variation in vaccine coverage.

And what happens when you have variation in vaccine coverage is that you can have pockets of the population that have very low vaccination rates, and this does lead to outbreaks. We can see this in the data. And what we also see in the data, and I do think this is really interesting, is that a lot of the outbreaks do tend to happen in populations that choose not to vaccinate. Right. So, for example, a recent review found that 70% of measles cases that happened in vaccine-eligible individuals, meaning not including the babies that were too young to be vaccinated, 70% of those cases were among children with. non-medical exemptions. So that's personal or religious exemptions to vaccination. In pertussis outbreaks, and what's interesting about pertussis outbreaks is that unlike measles outbreaks, we do see pertussis happening in previously vaccinated people because immunity can

wane as you get older with the pertussis vaccine. That's why they recommend boosters for the pertussis vaccine. But even among pertussis outbreaks, between 25 and 45% in some outbreaks of cases were among unvaccinated or under-vaccinated individuals. And very often, a large percentage of those unvaccinated individuals are what they call intentionally unvaccinated. Yeah. So for the 70% of measles cases that happen among vaccine-eligible kids, I presume? Yes, kids. What is the other 30%? So it was 70% of cases were children with non-medical exemptions.

So then the other ones might have been kids that had either medical exemptions or another reason that they weren't vaccinated. Okay. Other than being too young. Okay. So that 30% is they may not have been able to or they didn't for some other reason, but it wasn't a non-medical exemption issue. Yeah. Yeah. Okay. They could have also been under-vaccinated. So studies have also found that the kids who tend to be completely unvaccinated and especially intentionally unvaccinated. So families who are choosing to not vaccinate their kids, those kids tend to be from. families of higher socioeconomic and higher education status. Yeah. Whereas kids who are under vaccinated, meaning they have some of their vaccinations, but not all of

them, and those kids are still at risk for getting disease, those kids tend to be from families of lower education and lower socioeconomic status, which suggests that they might be facing barriers to getting vaccinated. So that's a pretty huge deal. Right. It should be, I mean, vaccination should be easy and, um, affordable slash completely free. Speaking of my opinion, I would agree with you entirely.

So let's talk about what the costs of vaccinations are. Fantastic. What a transition. So in the U.S., if you have health insurance, vaccines are covered. All of the recommended vaccines are required to be covered by your health insurance provider. Okay. So you might have co-pays or other out-of-pocket fees. You might have to pay facilities fees at your hospital.

no shade, show so much shade. But the vaccines themselves are covered by health insurance in the U.S. However, this is only true for recommended vaccines. So if you, for example, are outside of the age range of what is recommended for the HPV vaccine, your insurance is not required to cover that, which means it will cost you $200 out of pocket per vaccine, by the way. And so this also applies to travel, like travel vaccines, yellow fever and typhoid and so on. Yeah, so those are pretty expensive. What was the yellow fever one? Like 150 bucks or something? At least, I think it might have been a little more. Yeah. If a child, so if we're talking about childhood vaccines, which is most of what we've talked about so far in this episode, if a child does not have insurance in the U.S.,

they qualify for the Vaccines for Children's Program, which is a federally funded program that covers the cost of all the recommended vaccines for children. It is not always super easy to access. I think in general, you have to go to a federally qualified health center to get those vaccines. So, for example, in Champaign, kids can go to some school-based health clinics or the Champaign Public Health Department. But in theory, there are programs in place to make sure that kids, even if they don't have insurance, have access to vaccines. Doesn't mean that they're always getting vaccinated. around the world, every different country does things a little bit differently. So some countries have entirely free vaccines. Some countries like Australia actually pay people to vaccinate.

That's, I love that. Me too. I think it's so great. Because some countries also find you if you don't or if you're not up to date. So it's like, ooh, different stroke. Well, I'm positive reinforcement, negative reinforcement. Right. Both are effective. kind of one might be more than the other right um and then there's also something called the global alliance for vaccines and immunization gavi or gavi i don't know let's say gavi because it sounds fancier gavi gavi gavi gavi was established gavai i like that let's go with that gavi they're going to hate us was established in 2000, and their goal is improving vaccine coverage around the world.

So they provide funding for a number of different vaccines for countries to establish vaccine programs, to keep them up and running, and things like that. The Bill and Melinda Gates Foundation helped Gabi, helped them get started. And in the first 16 years of the program, more than 640 million children had access to vaccines because of Gavi, and it's estimated that more than 9 million lives were saved.

Awesome. It's pretty great. And then the World Health Organization in UNICEF also have programs in place to help subsidize the cost of vaccines in a lot of countries. Fantastic. And to bring you even more information about the future of vaccines and vaccines initiatives and what's really going on around the world today, we talked with Dr. Padmini Streikentaya, who is another senior program officer at the Bill and Melinda Gates Foundation.

Dr. Shrikantaya, thank you so very much for taking the time to chat with us today about vaccines. Could you introduce yourself and tell us a bit about what you do as a senior program officer at the Gates Foundation and maybe a bit of your background? Sure. So as you know, my name is Padmanee Shrikantaya. I am an infectious disease physician by training and also an epidemiologist. So I trained in internal medicine but knew I was interested in public health. And about almost 20 years ago, trained at the CDC in a program called the Epidemic Intelligence Service, which is a training program and applied public health and epidemiology. And since then, have been focused on infectious diseases in public health. And I came to the Gates Foundation about a year and a half ago.

and here I work in the global health division in the pneumonia team, which is headed by Dr. Keith Klubman. And I lead three initiatives or initiatives on three different pathogens or syndromes. One is on antimicrobial resistance or antibiotic resistance. The second is on a virus called respiratory syncyticial virus, which is a leading cause of pneumonia in young children and especially in infants. under six months of age. And the third is on influenza, which, as you know, is a major killer globally and here in the United States as well. Very cool. Yeah. So I think when a lot of us hear about vaccines, we usually think about the vaccines that we got as children, like the MMR vaccine or the DETAP vaccine or even sometimes the seasonal influenza vaccine. But there are so many

other vaccines out there that are incredibly important and save millions of lives and also help to reduce poverty worldwide. So can you tell us about some of the global vaccine initiatives that are high priorities at the Gates Foundation? Sure. So within the pneumonia team, actually, I can tell you that we are focused on vaccines as our major lever for preventing the infectious pathogens that cause pneumonia and lower respiratory tract infections, which remain among the leading causes of mortality among young children under the age of five. So within the pneumonia team, our focus is on the pneumococcus, which is a bacteria that causes pneumonia and invasive disease, and for which there is a very effective vaccine, which has been in use in the U.S. for a number of years and has shown

remarkable reductions in invasive infections due to pneumococcus as well as what's called herd immunity. In the area that I'm focused on, we are very interested in the and keenly working towards the development of a vaccine for RSV, or respiratory synestitial virus, as they mentioned, And very important and one of the leading causes of pneumonia and an important cause of pneumonia-related mortality in infants under the age of six months. So this population is particularly because the mortality is seen in very young infancy in the first three months of age. This population is a, it presents a important or presents a challenge for how we approach values. vaccination. And in this case for RSV, what we're pursuing with our partners is maternal vaccination. So in this scenario, a pregnant woman is vaccinated in her third trimester of pregnancy, mounts an immune response to the vaccine. And those antibodies are passed through the placenta to the fetus. And so the baby at birth now has levels of antibodies that are protective against against RSV or the idea that they would have protective levels of antibody against RSV,

and then those young infants would be protected against pneumonia for their first few to several months of life. So RSV is one example, and the field is full of a number of other developers who are working on vaccines to protect both young infants as well as elderly populations who are also at greater risk of severe disease and poor outcomes. The other that I'm focused on or that we are focused on in the foundation is influenza. And as you mentioned, right now, much of the effort for influenza is on seasonal influenza vaccination. The goal and the focus of our influenza vaccine development efforts is really on universal

influenza vaccine. So this idea is that a vaccine that is effective against the strains of influenza that are circulating, and then as well as the strains of influenza that may emerge, particularly the concern is for pandemic influenza or influenza that is dramatically different than what the circulating strains are. So this is a tall order, and this is our effort. efforts through our partners are in pre-clinical stages primarily at this point, but I think this is what we're really aiming for with influenza. And maybe the last thing I'll talk about is the work that I'm doing with our partners, again, on antimicropial resistance. Most of the efforts and most of the focus globally when people are talking about antimicrobial resistance has really been on specific.

bacterial and fast-growing bacterial pathogens, but specific to the efforts that I want to mention today are trying to understand the burden of disease due to resistant pathogens and bacteria in particular. And in our efforts, our focus is really on neonatal or newborn subsist, and pathogens or bacteria that are causing sepsis and mortality in these populations. then become our potential target for vaccination. And maybe that's a good point to just mention in terms of how we select what are targets for vaccination. It's really driven by trying to understand where the disease burden lies and where mortality

and disease mortality lies. And where there is that significant burden of disease burden and disease mortality will be our focus for trying to figure out what is the best method of preventing this illness and how could vaccines potentially be an important and successful lever. So maybe I'll stop there and turn it over back to you. Thank you so much. That was incredibly thorough. And yeah, you really did raise a lot of interesting and very important points, particularly in terms of vaccine development and targets and sort of, you know, jumped our questions. bit. No, that's great. Anticipated our needs. Yeah. So one of the things about a lot of these

global vaccine initiatives in the places where they are targeted, resources might be limited or there might not be a strong public health infrastructure set up yet. So what are some of the challenges that you face on the ground and actually getting vaccines to the people who need them? And how are you at the Gates Foundation working to overcome those challenges? Yeah. So, Within the foundation, there is a large group and team that actually works on vaccine delivery that is really focused on a lot of these issues that you raise. And I think that one of the things is many of the countries where we're focused in South Asia, in sub-Saharan Africa, where health systems aren't that strong,

most of these countries do have routine immunization programs. And we certainly advocate for countries to invest. further in their routine immunization programs, which lays the foundation not only for a stronger health system, but also helps to protect the most vulnerable populations and therefore have a more resilient population as these young children grow up. So in terms of thinking about these challenges, one, for example, that I can mention is when we are interested in maternal vaccines. And maternal immunization, where we have to think about not just the challenges in a routine immunization program where children will be brought at certain time points.

You mentioned, for example, at birth, at six weeks, at six months or nine months, and thereafter at routine immunization time points. Here, in a maternal vaccine situation, we actually need to target the mother, the pregnant mother in the antinatal care system. And so our challenge has been together with many experts and colleagues in the field is to figure out how when we do have an effective maternal vaccine like for RSB or Group B Strep or other pathogens that we feel are important pathogens to target with maternal vaccination, we'll need to figure out and we're working hard to try to figure out how do we access and how do we work with the obstetric and antinatal care populations to leverage those

platforms and help to strengthen those platforms to provide immunization to the mother that will ultimately protect the infant. While we see these challenges, we also see that many of these interventions and particularly vaccination interventions can be used in and of themselves to help strengthen and what might not be the strongest health care systems to begin with. That's excellent. And kind of really leads into the next question we were going to ask you, which is that we talk in this episode about how the benefits of vaccines, you know, include that you are protected and like you mentioned,

herd immunity, your neighbor is protected from infectious disease, but vaccines are indirectly tied to a lot of other improvements in health and poverty reduction. So can you talk a little bit more about how this works, how vaccines have had this very multifaceted impact on health and the economy? Yeah. So, you know, I think that vaccines, I think, what is one of the things important to remember is vaccines are one of the most cost-effective health tools that have ever been invented. Every dollar spent on childhood immunization returns up to $44 in economic and social benefits. And while we prevent a specific illness through a vaccine or a specific

pathogen. Many of these illnesses, RSV is a great example when an infant contracts RSV. Not only are they at risk for the poor outcomes of the RSV infection, not only does that lead to the infection and episode of that acute illness, but they are also then potentially at greater risk for subsequent infections. So you can see how for a family where each health health shock is a potential for a drop in economic gains. Not only are they concerned about the health and well-being of that one child, but that illness impacts their ability to earn as a family, their ability to provide for themselves and for other members in the family,

that if there is a subsequent super infection or a subsequent pneumococcal infection, for example, then there is a whole next shock that actually happens. And through vaccination, if you're preventing that first instance, you're actually helping to prevent that cascade of events as well. Yeah. So can you tell us, maybe point our listeners in a direction to where they can find more information on the work that you and that the Gates Foundation is doing? Sure.

So I think the best place to go is just to, our Gates Foundation website, which is www.gattsfoundation.org, and they'll be able to navigate through the plethora of different global health efforts that the foundation is engaged on. I've just touched on just a few that I'm specifically involved with in the pneumonia team, but within global health, there are teams that are focused on TB, on HIV, on Antaric and diarrheal disease, other pathogens within pneumonia, malaria, as well as neglected tropical diseases, just to name a few. So I hope your listeners have a chance to learn more about all of these different efforts. Great.

We do too. Thank you so much. I think those are all of the big questions that we had for you today. Thank you so much for taking time out of your busy schedule to talk with us. We really appreciate it. And I feel like we covered so much ground in a short time. Yeah, thank you. My pleasure. Thanks a lot. That was so amazing. It was so cool to talk with both Dr. Strykantaya and Dr. Rogers and to get more insight into how vaccines actually are developed and also like what vaccines are targeted and what's going on around the world. That was amazing.

We're so lucky that we get to do stuff like this, Erin. It's been thrilling. Thank you so much to Amber Zettis for setting all that up. Yes, Amber, hero, champion. You know how earlier I kept listing all the different numbers about vaccines and lives saved and so on. We've had so many incredible numbers in this episode. So many numbers. Okay. And I'm going to add just one more. Oh, good.

Sorry about that. But so it's a number related to the Gates Foundation that I came across recently that estimates that since 1990 an estimated 122,000, an estimated 122,000. million lives, mostly children, have been saved by the work that the Bill and Melinda Gates Foundation has done. Wow. That's incredible. Isn't that amazing? That's incredible.

So overall, vaccines are safe. They're effective. And we know that there's a lot of misinformation out there right now about vaccines. So next week, next week, you don't have to wait two weeks. Guys, this is a surprise. We're doing this a week early. Because we don't want you to have to wait a single more day. So next week, we will be addressing the history of vaccine hesitancy, which as it turns out, isn't so modern.

No. And then we're also going to address a lot of the specific concerns that you have, that you've written to us about, and that many people have about vaccines so that you can feel good about them and you can explain to your aunt Martha why she should. should feel good about vaccines too. It's going to be fantastic. Oh, it's going to be great. And we have such great guests lined up. We can't wait to tell you about it.

Yes. Oh, my gosh, you guys. All right. So should we do sources? Yes, absolutely. Okay. I have a few books that I've read. Vaccines did not cause Rachel's autism by Dr. Peter Hotez.

So good. So good. Really good. Between Hope and Fear by Michael Kinch, deadly choices by Dr. Paul Offutt, and the vaccine race by Meredith Wadman. And I have some papers as well that I'll post. And I also wanted to give a shout out to some multimedia. So there's a Nova episode. I believe it's called Calling the Shots.

And that's about vaccines today. It touches a little bit on the history, but it has some great information and some great interviews with different people. Excellent. I have more sources for this and next week's episode than I've ever had in my life. So we're going to post all of our sources as we always do on our website. This Podcast Will Kill You.com under the episodes tab. You can find every single source we've ever used for every episode.

Yeah. Yeah. So. So thank you to Bloodmobile for providing the music for this episode and all of our episodes. And you can find Bloodmobile's music now on Bandcamp. Band camp. We'll post a link on our website, but I think it's the real Bloodmobile or something like that. Okay, cool.

Yeah. And also thank you to you all for listening. Thank you so much. This was a really fun episode, and we hope that you loved it and learned a lot. And we can't wait for next week's episode. It's going to be so fun. Okay. Wash your hands.

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