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Ep 26 Vaccines part 1: Let's hear it for Maurice

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Published May 14, 2019, 7:00 AM

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/

 

I am one of the increasingly rare old timers who lived during the pre vaccination era. I am the second to the last of thirteen 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 protessis 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 protessis 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 limps. As a third and fourth year medical student, I remember answering the 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. Jean Gangarosa, who was a professor emeritus from Emory University. He wrote that letter in two thousand. Yeah, it's it is amazing. He's very right. We do forget. And those of us who have never heard it don't know, right, Yeah, we don't know what it's like. My name is Aaron.

Welsh and I'm Aaron Oman Updyke.

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, doctor Gail Rogers and doctor Pedmini Shrikantaya, who are both senior program officers at the Bill and Melinda Gates Foundation. We chatted with doctor Shrikantaia and doctor 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 day tuned. Okay, so what are we drinking today? It's it's vaccine time.

Quarantiny time, quarantiny time. We're drinking wait for it.

Enders fame, finally, finally, Yes. So this quarantini is named for John Enders, who is the recipient of a Nobel Prize for his work on how on cultivating the poliovirus, 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 konnac orange liqueur and lemon juice.

Is basically a sidecar.

Yeah, so fancy little fancy, little fun drink, and we'll have the full recipe for that quarantini as well as our non alcoholic plusy burrita on all of our social media channels as well as our website. This part okays We'll kill You dot com.

Yeah, check it out, check 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 epidemiology, or podcasting or cocktail techniques or honestly whatever you can think.

Of anything you want to know, So send us your questions by email to this podcast will Kill You at gmail dot com.

And if you decide to send us a question that you want us to answer for this episode, please put ask the errands 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 shark 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. 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 see 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 immuneologists don't hate me. I'm going to break this down in the simplest possible way. 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 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 gonna have a play.

Oh my god, mine's the four parts too.

Oh my god, we didn't even plan that.

Oh we didn't.

Okay, thrilling, Oh my goodness.

Okay, so we're uh biology play first four X.

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 gonna 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.

It's nice.

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 incomes the macrophages. The macrophagers are going to see this antigen, this virus or bacteria, and they're going to eat it. They're gonna gobble it up, and they're gonna take that and take a part of it, and they're going to bring it over to their friends who enter stage left. The tea cells and the T cells walk in and they're like, hey, macro how's it going. What you got 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 too.

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 tea cells they're a little wacky, they're a little wild. Okay, they're called the cytotoxic tea 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 gonna exit and they're gonna go start replicating like wildfire, and they're gonna 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 gonna go out and kill it. They're just gonna start murdering things throughout your body.

Okay, okay, shoot first, ask questions later.

Exactly.

So those are the cidotoxic mohawk tea 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 gonna 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 nodebar, they call out amongst the thousands of B cells just hanging out and they're like, hey, hi, everybody, does anyone recognize this anigen? Mcriface 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, swingy Western doors. You hear the clink saloon doors, saloon doors.

There you go.

You hear the clink clink of spurs and in walks wearing a ten gallon hat a B cell and he says, I sure do, I sure do recognize that antigen. And then they get to work actually immunity. So ten 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 specific. 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 and attached to that anigen 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 anigen 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. They can come in and clean up the mess. They take soldiers exactly, So they come in and destroy that infection.

Okay, So can I just review absolutely? Okay. So the macrifhage picks something up weird and then they bring it over and they're like, okay, everyone, T cells, B cells, what is this?

Mm hmmm.

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 anagen. So it's not going to go out and just kill anything that looks similar to it. It'll just okay, 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? So then that makes the killer T cells.

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 ten 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. Maybe 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 rigamarole of acts one, two, and three. They'll just be able to use the antibodies they've already have in the mem resells to make more copies and identify and target that anagen and quash the infection before it ever takes hold. So this is the principle that vaccines exploit. They expose you to an anigen, 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 exactly, 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 you're immune cells in a lot of cases, if 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.

Mm hmmmm cool yeah, cool, it's fantastic. I mean, vaccines are the best.

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 ninety seven percent of one hundred people are vaccinated, that means that those ninety seven 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 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 fifty percent of people are vaccinated, then only fifty percent of people are immune and the other fifty 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 forty nine 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 rubella, which you talked about before, and also verisicella, which is chicken pox. 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. Through this type 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 immunal compromised, 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 vasvaccines. 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 poliovirus, the one that is an injection or the influenza vaccine.

And so are there also killed bacteria vaccine?

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 immuno compromised 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, yes, this means.

This means.

That you cannot get the flu from the fl vaccine.

Correct, absolutely not ever so more, 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 aarin 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 will like you could, like you might if you've 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's mostly where there is still a chance of polio infection, like wild type polio still circulates in about one in two point five million doses. 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 vericella vaccine and then end up getting a rash, you could potentially then pass vericella to somebody who's immunal compromised 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. 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.

Uh, diptheria, diphtheria.

Also tetanus. Okay.

I think that toxoid vaccines are my favorite, and I don't know why you know they.

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 question answer.

Cholera produces a toxin. Is the colera vaccine toxoid or is it?

That's a good question. I'm pretty sure that it is. I was just looking at the color of vaccine. I think I wrote it down.

No, I have it right here. Hold on. Okay, So the one that was produced in eighteen ninety six was killed whole and then the second one that was in nineteen ninety one is also kill killed whole cell, whole cell vaccine, and then the one in two thousand and nine was also killed whole cell.

Okay, killed wholes So cholera is a killed whole cell 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 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 your cells. So we have some vaccines like that that are just made of a single component of a virus.

Okay, and do they are there also component bacterial vaccines, Yeah.

There are, for sure, But what's more common for bacteria 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 ten galon and the helper T cells, those only work if the anigen is a protein.

Mmmmmm.

So what we figured out to outsmart these bacteria who have 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 tetanus toxoid, 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.

They're my favorite, so very cool.

That's how we got vaccines for hemophalous influenzae, nicicerium, and ingititis.

Et cetera.

So those are I think definitely the newest vaccines are conjugate vaccines. Well, even newer are the DNA vaccines, which I'm not going to talk about today. But how fun right, that's amazing, very cool question.

M hm.

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 doctor 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 doctor 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 gonna let her answer.

Take it away.

Gail.

So, doctor 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 in 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 in a hospital and 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 dengay 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 it's a pretty lengthy process and and that that's something that and as and I think the right word is rigorous, as you as you mentioned.

So it starts out in somebody's idea.

Of doing this, and usually there is a pre clinical stage, which is when it is looked at in the laboratory. Uh, 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 and that really is for safety reasons.

And then it 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 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 three studies, in which it's tested.

In many more children.

In different schedules, sometimes in different countries UH and really rigorously tested under under many circumstances to make sure that they're safe and that and then this is the one that they 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 one hundred years have been incredibly productive for vaccine development, especially the past forty years, even the past ten 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 it's really it really is 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 being targeted.

And then what makes.

One more successful than others, I think is the wide variety of the pathogens and how often they can change, which is is pretty daunting.

For example, I know you talked to to Padmini and.

She runs influenza, but influenza changes so frequently that the target forgetting one vaccine to cope against all all types is really challenging.

In I can tell you specific case.

Of the numacaccus, 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 nineties when the technology was became available to know how to how to actually compose the vaccine to make children's immune system react to it, that 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 numacaccus, for example, there's over ninety zerotypes they're called that cause pneumonia, and it's hard to envision trying to do this for all ninety. 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 ten.

Zerotypes and thirteen two different vaccines that target those zerotypes 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.

I think we are, you know, we're aiming to do to you know, challenge and really try to control the worst.

Of the pathogens as as they become more prominent.

So I think that for one, technology is helping us to to try to get to a universal influenza vaccine. So old pathoges that we know of, but what I'm kind of really interested in, and you know, not directly involved with the development, but really see as new diseases come up that are truly worldwide threats, such as bola, such as zeka, that it's pretty now clear that advances can be made pretty quickly in these fields with with the new with new technologies that will lead us to having vaccines, for example, for vola, in a time span that was really unreachable or inconceivable before. So I guess I'm kind of hopeful for a response time.

In the future.

I'm hoping, uh for antimicrobial resistance a vaccine for that that would be multipathogen I mean, this is really a.

Dream as as organisms they're pretty smart and they can outdo antibiotics quite quickly. I think that you know, going the potentially going the vaccine route is going to be important.

That's really exciting that the idea of a vaccine for multiple pathogens that are anti microbial resistant. I I just in my mind just went.

Well, that's a dream, but you got a dream big and yeah, and you know, just seeing for example, there there are other things as well that I think I can point towards that are really interesting on a different realm, which is trying to get what we what we strive for 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 that low resource countries could afford them. And now they're innovative financing mechanisms and you know, involving cheered pricing, et cetera. So at the same time that they're licensed in the US, in Europe and used in middle income countries.

They can be used in low income countries as well as well.

And that's I mean, that's particularly exciting to have that kind of 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 dot gov website. They have a really of what's available as well as, uh, what's what's up and coming. There's also the Clinical Trials dot gov that that tells you all the trials that are that that are being done with with vaccines as well as with with other drugs. So certainly so those are those are really good resources for for you to look for that what's what's up and coming?

Fantastic, Thank you so much well, doctor 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.

That's all I have for the biology is like a whole immunology course.

Yeah, I feel armed with knowledge.

Great well armed me with the.

Okay, we'll get ready to learn. There's a lot of history here.

Let's take a quick break. Huh.

All right, let's do it. For this episode, I'm going to give an overview of the history of vaccine development and the observed effects and 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 bets, 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 as 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 seventeen ninety six in England from a cowpox or 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 vaccines 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 two hundred BCE. Wow. Yeah, it's amazing, 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 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 disfiguring leshmaniasists by scraping an active lesion of someone with the disease and putting it on a child's arm or button.

Really yeah, I know.

And so there isn't a licensed leshmanias's vaccine today, but people at the Texas Children's Hospital Center for Vaccine Development are working on it. Okay, back to back to variolation, slash and oculation. 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 just like do a lot of ground up yeah, so gross, So people actually injected the infectious material just under the skin. So this is varilation. 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 varilation 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, smallpoc.

Vaccination, as we all know, was developed by Edward Jenner in seventeen ninety six, and the story we all know and love. Jenner, who already knew about varulation, had his revelation when he realized that milkmaids never got smallpox because they were protected against it after being exposed to cowpox, loer infections bloh blah.

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, well Jimmy jim, inoculating him first with cowpox on May fourteenth, seventeen ninety six.

That's the day this episode's being released. Yes, oh my god, did we do it on purpose? One hundred percent?

No, No, definitely not.

This is my favorite serendipity. I love it. Two hundred and twenty three years ago. Today, on the day that hopefully a lot of you are hearing this, yeah, 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 hence the title vaccine so her hide. Blossom's hide is displayed at Saint George's Hospital in London. So if there are any London listeners that are out there, please send us a pic. 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, twenty years before Jenner's vaccine emits a smallpox out break 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 gonna grow horns and utters and they're gonna 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. Wow, 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 the first. This first vaccine would light the way for the development of so many more. Act two Chance favors the prepared mind, even though vaccination got him 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 sixty or seventy years after Jenner first vaccinated FIPS 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 Pasture 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 if that's what motivated him. In the eighteen fifties and eighteen sixties, Pasture, 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 in 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 eighteen eighty, so, almost one hundred years after Jenner's vaccine, Louis Pasture 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 maltacida 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 in wild and domestic fowl.

Woh, poor baby.

Yeah. So Pasture just set off for holiday, leaving his search 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 Pasture did, and when he got back he saw the test tube with avian collar 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, wow, 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 good. He's like, I'm about to get fired, but I have to tell the boss. So he fills in Pasture on the results, and Pasture is like, oh my gosh, are you kidding me? This is the most exciting thing. What do you mean do this 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 pest. You're like, I gotta tell my boss I really screwed up, and they're like, this.

Is the best news.

Yeah, it's like that genius. So then that's what Chamberlain does, and again the chickens remain healthy and cholera free.

Oh my gosh.

Both Pasture 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 colera vaccine was made from the same species of bacteria themselves, so you didn't have to find a milder strain or species crede a vaccine like the cowpox virus. In this pox virus, you just had to weaken the existing one. 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 Pasture's Avian collar of vaccine was not a fluke. In the summer of eighteen eighty one, Pastures successfully produced an anthrax vaccine by attenuating the bacteria using phenol. 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 cow and sheeps and goats and so on. Pasture decided to keep the name vaccine as a nod to Genner, and the story of vaccines was about to enter its heyday, Act three, 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 road map 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 eighteen eighty five, Pasture developed the rabies vaccine, which I talked about in the Rabies episode, and then Almroth Wright, Richard Feiffer, and Wilhelm Cole developed the first typhoid vaccine in eighteen ninety six. That same year, Waldemar Mordecai half kind developed a collar of vaccine Yeah what a name, which he promptly tested on himself and then narrowly escaped with his life apparently. Yeah, but he decided.

Super effective vaccine there.

Wow, he thought good enough, so he tested it 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 out his collar of vaccine, half Kind 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 eighteen ninety seven, 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. Actually, fortunately the vaccine did work without serious side effects, and his quick work probably saved thousands of lives. However, his fame accolades were short lived. In nineteen o two, after being given the plague vaccine, a bunch of people developed tetanus symptoms and nineteen died. Ooh 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 forceps in the dirt and didn't bother to clean them or get a replacement. Tetanus loves soil. It loves to live in soil.

Yeah, oh that's so awful.

Right, yeah, sterile technique important, very so. Eventually half Kind was publicly exonered, but the damage to his reputation was already done and would never fully recover. Half Kind's contaminated plague vaccine is a perfect illustration of the lack of oversight on vaccine development during this time. While all of these vaccines and antitoxins were being produced in the late eighteen hundreds, 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 nineteen oh one, the year before Half the Half Kind incident, some smallpox vaccines and dip theory antitoxin were contaminated with tetanus and twenty four 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 nineteen oh two, Teddy Roosevelt signed into law the Biologics Control Act, which would require that health commissioners oversaw vaccine production. Just 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 diseases for which there was no effective treatment or protection. In the nineteen twenties, researchers started to experiment with adjuvants, which comes from the Latin for 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 formuline, which had been used just to preserve antitoxin, also actually inactivated the toxins. So this allowed him to develop the diph theory of vaccine. In nineteen twenty three, 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 sixty million lives saved estimated.

Geez.

Next was Protessis. Protessis aka Whoopincoff 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 Protess's vaccine in nineteen forty that would be used up until the nineteen nineties.

Wow, which just pretty dope.

Yeah, Goo, ladies. During the nineteen thirties, vaccines against influenza, tuberculosis, the BCG vaccine and yellow fever were developed, with Max Tyler earning the only Nobel Prize to be given just for the discovery 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 forgotten with the air quotes. The contamination of a batch of yellow fever vaccine that led to fifty thousand military personnel getting infected with hepatitis B during World War Two.

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 fifty six people, mostly children. I 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 in 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 culturable responded well to attenuation and had low mutation rates or strain diversity. Because these were diseases that were fairly straightforward to develop vaccines for, it was almost just a race to see who could publish their vaccine first. In many ways, it's pretty cool. By the nineteen fifties. Even though there was a smallpox vaccine, a rabies vaccine, a diph theory of vaccine, yellow fever vaccine, and several others, many terrible diseases, including measles, mumps, rubella, hepatitis, meningitis, hemophlus, influenza type B, and polio still killed or permanently disabled many many people, children in particular, act for cultured Why did vaccine development for diseases like measles, rubella, and polio lag behind that of diptheria, plague, and cholera. 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 diptheria, 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. It 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 it start in the mid nineteen hundreds, but 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, and 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 Lax 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 was.

Under same of Ender Shame, 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. Yeah, so he he got he got a master's in Middle English and he was all set to do a PhD on Middle English English. But he found himself. Yeah, he found himself rooming with an Australian bacteriologist. They became close buds. He was charming and Enders would tag along with him to the lab and he was like, Wow, what is this. This is super cool?

What are you doing?

I love this? And so he decided to get this doctorate in microbiology instead of Middle English.

It's everyone who studies Middle English who listens to this podcast, right, and then like.

Now I'm doing every biology and we're like yeah, yes.

By the way, those emails literally like break our hearts with happiness.

They're the most thrilling.

Oh yeah, absolutely. Okay. So in the nineteen forties, Enders began to doubt the conventional wisdom that poliovirus only grew a nervous tissue, and he decided to try to grow the virus on other types of human fetal tissue, which was successful. This was a huge turning point in polio research that would lead to the creation of the vaccine that saved countless lives and prevented so many cases of paralysis. This development also earned Enders and his two research partners, Weller and Robins, the Nobel Prize in Physiology or Medicine in nineteen fifty four. Using a similar technique, but monkey kidney cells rather than human feudal cells, Jonas Salk developed the polio vaccine in nineteen fifty two. Monkey kidney cells had been used for a while to grow and study viruses, but something concerning came to light in the nineteen fifties. Many of these cells, which were still being used by people like Albert Sabin and Hilary Koprowski to develop live polio vaccines, were found to be contaminated by a virus called SV forty SV meaning Simian virus forty just being random the forty one or something, 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 Koprowski and Sabin, which had been widely tested but not yet licensed, were found to be contaminated with the virus, and socks killed polio vaccine, which had been administered to millions of people around the world, was also found to contain viral particles of SV forty.

Wow.

So in those people who had already received the live vaccine, researchers found no antibodies for SV forty, which indicated that it didn't cause any major infection. But that's still a lot of unknowns YEA, And so after this initial study that notified researchers of the presence of SB forty, a researcher named Bernice Eddie 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. No, not great. She published her work, which contributed to the general controversy and concern that was being raised about the existing Salk and Saban 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 regulars were put into place to prevent the contamination of the polio vaccine by SV forty. By the time people were like, Okay, this is actually a big deal. Over ninety eight million Americans had received the Salk vaccine, which had at least inactive and very possibly active SV forty particles in it. Okay, So another researcher who tried to sound the alarm bell about SV forty was Maurice Hillman, who would go on to become the most prolific vaccine developer ever ever, surpassing even John Enders. His name should be a household name, but he was just super modest. He and his team developed vaccines for over forty diseases, over forty vaccines. What his work is estimated to save eight 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 SV forty infected cells could not be considered safe, which meant massive and expensive 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 Weistar Institute in Philadelphia, Pennsylvania, under Hillary Kapowski. He had developed a strain of cells from human feudal 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 WI thirty eight, came from a fetus that had been aborted by a woman in Sweden in nineteen sixty two, where abortion had been legal since nineteen thirty eight. I also want to point out here that tissue from aboard of 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. 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 WI thirty eight 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 WI thirty eight cells. Many who had spent years developing vaccines using monkey kidney cells, like Albert Saban, weren't ready to trash their research program and start anew despite the promise the WI thirty eight cells had others express caution.

These cells were new.

Time would perhaps tell whether they were safe, but not enough time had passed yet, so WI thirty eight cells, particularly in the US, 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 Koprawski.

These are some great names, by the way.

I know right. He had witnessed the rise and concern about viruses contaminating monkey kidney cells and became convinced that Hayflick's WI thirty eight cells were the way to go. A couple of years after Hayflick had published on these cells, a devastating rubella epidemic in the US resulted in twelve point five million infections what one in fifteen Americans Holy guawk. Twenty one hundred people developed encephalitis, six two hundred and fifty pregnancies ended in miscarriage or still birth. Five thousand women chose to get abortions because they had been infected during pregnancy.

Congenital rubella is terrible yep.

Twenty one hundred infants died soon after birth, and twenty thousand babies were born and survived with congenital rubella syndrome h twenty thousand.

Oh my my heterus.

These numbers are actually probably an underestimate because physicians weren't required to report rubella 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 rubella vaccine using w I thirty eight cells, decided to test his out to be blunt. It wasn't great, didn't work. Many toddlers in the experiment straight up developed reubella, 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 eighty six degrees fahrenheit or thirty degrees celsius weakened the injected rubella enough to not cause any disease or side effects, but left it strong enough to produce antibody's and lasting immunity.

Wow.

Despite Plotkin's WA thirty eight 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 Plotkins WA thirty eight based vaccine was dropped from production in nineteen seventy, 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 thirty eight one. Her name was Dorothy Horstman and she was a pediatrician and vaccinologist at Yale Medical School. She found that eighty percent of those who received the commercially available rubella vaccine became reinfected within a few months. Really bad, not eighty percent, that's a lot yea. 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 Plotkins 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 Horsemen's research, Plotkins WA thirty eight Rebella vaccine was finally licensed in nineteen seventy eight, and the only other competitor, a vaccine made from animal cells, was withdrawn the following year. Wow WI thirty eight cells have gone on to make vaccines that have been given to over three hundred million people, and similar methods were used to make an additional six billion vaccines.

WHOA.

These vaccines have saved millions of people from horrific deaths or excruciating infections or debilitating disabilities from infections like rebella, rabies, chicken pox, measles, polio, hepatitis A, shingles, and adinovirus. They've been so integral to the development of vaccines, to laying the groundwork for our understanding of how celles 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 Wood. 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.

No, of course, those high counters got eleve 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 thirty eight cells if you can believe it, and if you want to learn more, I recommend the.

Book The Vaccine Race.

The widespread success of various vaccination programs led to record lows and 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 nineteen eighty, with the last known wild case occurring in nineteen seventy seven in Somalia. The effort to eradicate smallpox left a larger legacy than just elimiting 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 they set up in the WHO also set up the Expanded Program on Immunizations EPI to do this. Throughout the seventies, eighties, nineties, and two thousands and beyond, more vaccines were developed, including ones for a chicken pox, strep, pneumonia, niceria, meningititis, hepatitis B, hemophlis, infalenza type B e Q fever, hepatitis A, rotavirus, typhoid, human papaloma virus. I mean, just it's amazing, tickboarn andencephalitis. Gotta 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, and this just compares us 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 twenty one thousand cases, eighteen hundred deaths. It's twenty first century annually zero cases, zero deaths. Measles in the US before vaccines annually five hundred and thirty thousand cases Jesus four hundred and forty deaths twenty first century TBD. I'll just say for now tentatively over one hundred cases annually. Yeah, average protessis annually before vaccines two hundred thousand cases, four thousand deaths twenty first century. On average, fifteen thousand, six hundred cases annually, twenty seven deaths. A lot higher than I thought. Actually, it's a lot.

Of waiting immunity with the protessas vaccine.

Yeah. Paralytic polio before vaccines annually sixteen thousand, three hundred cases, nineteen hundred deaths twenty first century zero zero.

Wow.

Rubella. In nineteen sixty nine, which is the last year before rubella vaccine was licensed, there were over fifty five thousand, five hundred cases reported to the CDC, and ten years later that number was eleven thy eight hundred. Between those years, the number of congenital rebella cases in the US declined by thirty six percent, but at the turn of the twenty first century, there were one hundred and seventy six reported cases of rebella and nine cases of congenital rebella.

Wow.

That amazing, That is absolutely incredible.

In two thousand and five, the CDC announced that endemic rebella had been eliminated from the US, and ten years later In April twenty fifteen, PAHO, the Pan American Health Organization, announced that endemic rebella had been eliminated from the Western hemisphere. It just got chills me too. It's hot in this room. Smallpox, there are so many of these. Smallpox in the first half of the twentieth century, twenty nine thousand cases and three hundred and thirty seven deaths annually. Zero obviously in the twenty first century. Yeah, it's gone. It's gone. Gonka tetanus in the first half of the twenty first century, five hundred and eighty cases and four hundred and seventy two deaths annually. Twenty first century, forty one cases four deaths. Before the vaccine homophlus influenza type BE caused meningitis, bloodstream infections, and pneumonia and twenty thousand children every year, killing one thousand of them and causing permanent brain damage and many more. When fear drove down vaccination rates, outbreaks happened in two thousand and eight. In two thousand and nine in Minnesota, Pennsylvania, New York, Oklahoma, and Maine, with at least four children dying because those parents chose.

Not to vaccinate them.

Okay, chicken pox. The incidents of chicken pox and shingles, as well as US hospitalizations and deaths because people do die from chicken pox and shingles.

Yes they do.

It declined by ninety percent after it became part of the routine skin schedule. Wow. And when a booster was added, the incidents fell another eighty one percent.

Wow.

No one younger than twenty years old has died of chicken pox in the US since twenty ten.

Wow.

Yeah, ok okay, two more numbers. It is estimated that the work done by John Enders and his teams and Here's Fame has saved over one hundred and twenty million lives as of twenty seventeen. And I said it before, but I want to say it again. Maurice Hillman's work is estimated to save eight 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 from Maurice.

I like it.

Yeah, Okay, I really like it. The need for vaccines has never diminished, and the recent resurgence in vaccine preventable illnesses only highlight their importance. Aarin, I'm hoping you'll tell me some good news about vaccines today.

All right, after one more shortbreak. 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 the one that the US does not vaccinate for, but that one the World Health Organization recommends as a general recommendation.

Does the US 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 reason, that's not entirely clear. It's not great at protecting adults, so it doesn't protect adults.

From getting t B.

Huh, yeah, it's 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 US 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 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 protessis hib homophluous influenza type B, the horrible one that causes meningitis, the new Macacco VAC which there's actually a couple different new Macaco vaccines, but this protects against meningitis as well as pneumonia. Okay, in children and adults. There's different ones for children and adults. Rotavirus, 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 US 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 eighty percent vaccination coverage. And so those are mumps, vericella which is chicken pox, and seasonal influenza. Great, so that's the US vaccine list. We actually also vaccinate against niceria meningitis in the US, which is truly horrible illness that causes meningitis, and that one is recommended by the WHO for some countries, So the US 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 US pretty soon. And then there's things like typhoid, cholera, yellow fever, tick born encephalitis.

Okay, I'm getting that this week. Yeah, that'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.

Some One thing 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.

The World Health Organization has numbers ranging from fifty percent of all children have gotten the polio vaccine who should have gotten the polio vaccine, like in twenty eighteen, eighty five percent 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 ninety nine percent coverage and in some countries you're gonna have extremely low coverage. And so even for example, in the United States, So the way that the US 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 back scenes if you have a very legitimate medical reason like a serious allergy or immunal compromise or something like that.

Right, I think 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 twenty seventeen twenty eighteen, in forty nine states that reported their vaccine coverage rates for kindergarteners. While you look at the US, overall vaccination rates were very high for things like DTP and MMR and verriicella, anything from about usually about ninety five percent. If you look at the whole United States, in Washington.

D C.

Which had the lowest coverage, it was only eighty one percent oof and in mississippy ninety nine percent coverage of kindergarteners.

Okay, interesting, Does Mississippi have a philosophical exemption?

No, they do not.

You cannot get exemptions for religious, philosophical, or conscientious reasons in Mississippi only medical page.

Yeah, I didn't know that. Fascinating.

That's so high five Mississippi.

Right way to go. So you can see that even within the US, 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 seventy percent of measles cases that happened in vaccine eligible individuals, meaning not including the babies that were too young to be vaccinated, seventy percent of those cases were among children with non medical exemptions. So that's personal or religious exemptions to vaccination in Pretessa's outbreaks. And what's interesting about Protessis outbreaks is that, unlike Meso's outbreaks, we do see Pretessis happening in previously vaccinated people because immunity can wane as.

You get older.

With the Protessis vaccine, that's why you need They recommend boosters for the protesters vaccine. But even among Pertessis outbreaks, between twenty five and forty five percent 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 seventy percent of measles cases that happen among vaccine eligible kids, I presume kids, what is the other thirty percent?

So it was it was seventy percent 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 thirty percent is they may not have been able to or they didn't for some other reason, but that it wasn't.

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 undervaccinated, 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 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 US, if you have health insurance, vaccines are covered. All of the recommended vaccines are required to be covered by your health insurance provider. So you might have copays or other out of pocket fees. You might have to pay facilities fees at you're a hospital. No shade show, so much shade. But the vaccines themselves are covered by health insurance in the US. 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 two hundred dollars out of pocket per vaccine.

By the way, and so this also applies to travel like travel vaccines, it does aid and so on.

Yeah, so those are pretty expensive. What was the yellow fever one? Like one hundred and fifty 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 US, they qualify for the Vaccines for Children's Program, which is a federally funded program that covers the cost of all the recomd and in 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 Champagne, kids can go to some school based health clinics or the Champagne 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 oooh or different stroke.

Well, positive reinforcement, negative reinforcement, right, both are effective, kind of one might be more than right.

And then there's also something called the Global Alliance for Vaccines and Immunization GOVEY or Gavy.

I don't know, let's say.

Govey, because it's a fancier Govy.

Govey.

Govey was established, Gavi Gavy.

I like that. Let's go with that.

Gavy.

They're gonna hate us was established in two thousand and their goal is improving vaccine coverage around the world. So they provide funding for a number of different vaccines for countries and to establish vaccine programs to keep them up and running and things like that. The Bill and Melinda Gates Foundation helped Gavy. Gavey helped them get started, and in the first sixteen years of the program, more than six hundred and forty million children had access to vaccines because of GOV and it's estimated that more than nine million lives were saved.

Awesome, pretty great.

And then the 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 doctor Padmini Streakantaya, who's another senior program officer at the Bill and Melinda Gates Foundation.

Doctor 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 Pudmini Shrikantaya. I am an infectious disease position by training and also an epidemiologist. So I trained in internal medicine, but knew I was interested in public health, and about almost twenty years ago trained at the CDC in a program called the Epidemic Intelligence Service, which is a training program in 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 doctor Keith Kligman, 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 sensicial 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 new macaucus, 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 US for a number of years and has shown remarkable reductions in invasive infections due to newmacaccus 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 syncesicial virus as they mentioned, 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 it presents an important or presents a challenge for how we approach 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 the against RSV, or the idea that they would have protected levels of antibody against RSV and UH, and then those young infants would be protected against pneumonia for their first few to several months of life. So r SV 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 influence of 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 a pandemic influenza or influenza that is dramatically different than the than what the circulating strains are. So this is a tall order, and this is our efforts through our partners are in pre clinical stages primarily at this point, but I think this is the what we're really aiming for with with influenza. And maybe the last thing I'll talk about is is the work that I'm doing with our partners again on animicropial resistance. Most of the efforts and most of the focus globally when people are talking about animicropial 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 bard of disease due to resistant pathogens and bacteria in particular, and in our efforts, our focus is really on neonatal or newborn subsis and pathogens or bacteria that are causing sepsists 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 the 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 leaver. So maybe i'll stop there and turn it over back to you.

Thank you so much. That was incredibly thorough and you 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 a bit. No, that's great, anticipated our needs.

Yeah.

So one of the things about a lot of these these global vaccine initiative 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 has 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 and 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, you know, 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 anti natal 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 a maternal vaccine, like for RSV or or group B strap 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 anti natal 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 what might not be the strongest healthcare 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 forty four dollars 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 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 superinfection or a subsequent new macoccal infection, for example, then there is a whole next shock that actually happens, and through vaccination, if you're preventing that first instance, you are 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 dot Gatesfoundation dot go RG 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 TV on HIV, on enteric and diarrheal diseases, 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 doctor Straikantaiya and doctor Rogers and to get more insight into how vaccines actually are developed and also like what vaccines are t targeted and what's going on around the world. That was amazing.

We're so lucky that we get to do stuff like this, Aaron, No, it's been thrilling. Thank you so much to Amber's Eddies for setting all that up.

Yes, Amber, here are our champion. You know how earlier I kept listing all the different numbers about vaccines and live saved, and we've had.

So many incredible numbers in this episode, so many numbers.

Okay, I'm gonna add just one more. Sorry about that, but so it's a number related to the Gates Foundation that I came across recently that estimates that since nineteen ninety and estimated one hundred and twenty two million lives, mostly children, have been saved by the work that the Bill and Melinda Gates Foundation has done.

Wow, that's incredibly 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, hmm, next week 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 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 doctor Peter Hotez.

So good, so good, really good.

Between Hope and Fear by Michael Kinch, Deadly Choices by doctor Paul Offitt, 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. Yeah, and that's 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 at next week's episode than I've ever had in my life. So we're gonna post all of our sources as we always do on our website, This podcast will Kill You dot com. Under the episodes tab, you can find every single source we've ever used for every episode.

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 band camp.

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 mudy.

This is 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 gonna be so fun.

Okay, wash your hands, you filthy animal.

U

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