The future of vaccines

0:00This is Stanford's The Future of Everything, and I'm your host, Russ Altman. Since we started this podcast eight years ago, it's become an archive of the amazing and impactful work done by my colleagues at Stanford University. In a time when the sheer volume of information available to us can make our heads spin and make it hard to determine what's accurate, I'm proud to be able to bring you experts in law, medicine, engineering, technology, and much more. Vaccines are safe, that they work, that we have saved millions of lives because of them. And to really trust in your, if you find somebody that you trust, ask that trusted person to show you data and facts about, you know, what your questions might be about.

0:47This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. If this episode makes you laugh, learn, or just roll your eyes, go ahead and share it with your favorite human. Personal recommendations are a great way to spread news about the show, grow our audience, and improve public understanding of the future of everything. Today, Bonnie Maldonado will tell us that vaccines have become controversial. Yes, but they save lives for sure. It's the future of vaccines. Just a reminder that today we're continuing our feature, The Future in a Minute, where I ask the guests some rapid questions and they give us, hopefully, some rapid answers.

1:25It'll be at the end, so stay tuned. And before we get started, another reminder to share this episode with people you care about so that we can grow the show and improve public understanding of the future of everything.

1:44so viruses have created a ton of human suffering smallpox measles rubella and many others hiv these have created diseases that kill people that disfigure people and that create lifetime disability but starting in the late 19th early 20th century we started getting knowledge and ideas about how to stop viruses through vaccination. There were some amazing, brave, and you'll hear about some, experiments that people did to test these ideas, and they started to work. And we know this because looking back 100, 200, even 700 years, we know that the rates of death from viruses have plummeted, especially in children and the elderly, and many, many of the bad outcomes have been significantly alleviated.

2:34And yet there's questions about whether vaccines are worthwhile. What's up with that? Well, Bonnie Maldonado is a professor of pediatrics, epidemiology, and population health at Stanford University, and she's an expert on viruses, how they work, how they are used, how they're approved by the agencies that approve them, and why the public has some issues with them these days. We're going to get into all of that in this episode of The Future of Everything. So Bonnie, let's just start with basics. Why have you dedicated so much of your career to understanding vaccines, how they are developed, and how are they best used?

3:11Well, I don't know. How far back do you want to go? As far as you want. I always loved science. I was always that kid back in the day. I don't think they have them anymore, but little chemistry sets and things like that. I was trying to figure things out. Didn't pull animals apart or any of that, but just trying to understand the world around me and just love the idea of science. It was just really fun for me. And then in college decided, you know, do I want to do a PhD in this new field called molecular biology, or do I want to go to med school, or do I want to do community work and do a master's in public health?

3:45So I kind of decided to go down medical school route because I thought it was the hardest thing at the moment and just like tackle the harder one first. Loved it. Wanted to do science and also serve communities. And I realized that the best way to do that was prevention. And there's no better place to start with prevention than the fetus and newborn. And I realized that 20 million children a year were dying from vaccine-preventable diseases, low-hanging fruit. And I love, love, love. I discovered I love, love, love viruses. not that they're my friends, but I love studying them. They're actually simple to study, which makes it easier than bacteria, et cetera.

4:28And realize that vaccines were a magic bullet. And I thought, why aren't we doing this? So that was, you know, 40 plus years ago. Now in retrospect, I thought, well, you know, it was a bit of an uphill climb, but it was the easiest climb of all the problems we've had to solve. So that's, you know, we now have 5 million children a year who die under the age of five around the world. Those are mostly preventable, but most of the vaccine-related deaths are gone now, which is great. Great. Thank you. So just so we get everybody on a playing field that's even, can we start with the basics of vaccines?

5:00Maybe a little history, you decide, but like, where do they come from? How do they work? What's the basic idea? So the basic idea of vaccines is to expose yourself to something in the environment, preferably that isn't harmful, that will protect you from all of the pathogens, all of the organisms in the world that are out there that I wouldn't say they're trying to kill you. They're just trying to survive like we are, but how can we either keep them at bay or be more symbiotic with these things? Now we know, and you're the expert here, there's a lot in the world that's out there that's good for us, right?

5:41That we never really knew about. David Relman, for example, created essentially this whole new field of microbiome. We talk about it like it's not a big deal. But I remember when David was talking about this idea of microbiome and we all thought, ah, I don't know how you're going to ever study that. We didn't have the computer capacity, et cetera. But we realized there's a lot of good out there. But then there's the occasional bad actors. And again, not to anthropomorphize them, but they basically are just trying to survive like we are. So how do we get them to not hurt us, to not kill us? And so what you do is you engineer something that's either in that organism or like that organism to then prime your immune system to recognize it so that when you see the real thing, you suppress it immediately.

6:29It's kind of like your frontline first responders. They come right out guns blazing and they knock it down. you know you might still get a little bit infected or sick but you're not going to get the full-blown disease you're not going to die and you're not going to have complications so that's it in a nutshell so what are the sources of variability in the response i know this is something that you study a lot i know that sometimes we have people who get a vaccine and it works great and sometimes there's like a breakthrough infection in the sense that you weren't supposed to get it but you get it So what do we know about the individual response to vaccines?

7:04Well, remarkably little. This is all hit and miss. And I think this is why we're seeing what we're seeing today around, oh, vaccines are toxic substances and we have all these bad effects. Because in reality, we have been able to knock out most of those products. We don't take them very far because we found out early enough that something might not The harm might be worse than the cure, if you will, because we don't really understand very much about not only the immune system and how it responds to different elements in the environment, but we also don't understand those viruses, bacteria. Each one is very, very different in the way it can cause disease or in the way we can suppress it.

7:48we've been very fortunate in spreading a wide array a menu of of ways to attack organisms in the in the in the world and figure out which responses work best and which ones don't work at all and so unfortunately that is something that i'm hoping we could learn better how do we understand our immune system it's incredibly complex i mean obviously the brain is more complex But the immune system is just, you know, very complicated. And we are basically hitting it at this point with a very wide approach. But again, we still are able to measure, we measure very broad outcomes like symptoms, harm, you know, are there symptoms that a vaccine will cause, for example.

8:35And we stop those studies immediately. So, unfortunately, we don't know much, but we do have general markers like, first of all, can you develop immunity? Can you develop an antibody response? Can you develop a T-cell response of some sort? Are T-cell responses as important as antibody responses? And then we study these in test tubes first. We study these in animals. We're going to have to move away from animals, which is not a bad idea, looking at biomarkers. And then can we take those into clinical trials? So it's a long, long process. It takes, you know, what, five to 10 years or more, sometimes multiple decades to develop an understanding of which vaccines work and which don't.

9:17But in the end, they're fairly crude markers of outcome. When we do study them and we see some side effects, is it the case that they look at how bad the infection would be and how bad the side effects? And is it like a little bit of a sliding scale? If it's a terrible disease, you might accept more side effects. Whereas if it's like inconvenient and like bad, but like not terrible, maybe you have a higher bar or is that not part of the calculation? Absolutely. You know, we're always, as we learned from COVID, this is always about risk benefit. I think everything we do every day from the minute we wake up until the minute we go to bed and in between is all about risk benefit.

9:57Should I cross the street? Should I drink this particular brand of beverage, et cetera? It's no different with organisms on a higher scale, obviously. So smallpox, for example, one of the greatest achievements of mankind or humankind is that we eradicated a whole disease that had been plaguing humans for millennia, we were able to eradicate smallpox. Now, the reason it needed to be eradicated is it had a 30 to 50 % mortality rate. And the people who survived had many, many complications thereafter. And the infection rate was pretty high. And it was a scourge. And there was something that you could do to prevent it.

10:43So why not try that. Now the vaccine themselves were not initially not eat. They had a lot of side effects, but they didn't kill you. I guess that was the bar, right? You didn't die, but you actually, you know, it did manage to cure you and you might've gotten pretty sick with the vaccine. So that's a good example at the one end of the scale. At the other end of the scale, let's just say vaccines for Lyme disease, which there have been vaccines for Lyme disease. And And again, apologies to people who've had Lyme disease. It can be a terrible illness with lots of complications. But in the overall scheme of things, it's not that prevalent that we know of.

11:22And it's hard to understand how to get rid of it or whether vaccines really work. And so the first round of vaccines were relatively safe. But nobody cared, sadly, because they thought, well, I don't live in an area that has Lyme disease or it's really not that bad for many, many people. And so it's also part of it is a market value, right? Is it really going to sell on the market, meaning our providers, our patients going to want it? So that's kind of the very rough way that these things are done. Great. And in fact, you mentioned smallpox and you made a reference to kind of deadly vaccines, deadly viruses.

12:00I always have wondered this, and maybe you can help me. Why would a virus kill us? And I know that sounds crazy, but like they need us to survive and to replicate. So is there an understanding of when a virus goes too far and actually kills its host and therefore is kind of shooting itself in its viral foot? But do we understand what's going on there? Nope. I mean, that's a teleological question. We have many of those, right? I have a whole book of teleological questions about these organisms. And you're right. Some of them don't make sense. Like anything else, they evolve just like we do. And sometimes they hit a dead end and they're gone, right?

12:38I mean, that happens to species throughout the history of the natural world. There are mistakes out there. And the smart virus, if you will, will live long enough, will let you live long enough to let it propagate, right? So here's a perfect example, HIV. HIV makes you, without therapy, it's 100 % fatal, we know. But it doesn't make you sick until 10, 20, 30 years into your infection. So you've been able to propagate that virus around the world in absent any treatment or prevention. and that's the perfect pathogen in some ways because we, and it also, the other really smart thing about it is it attacks your immune system.

13:25The host is your immune system. So not only does it take a long time for you to recognize it and allow it to spread, but it attacks the very thing that should be protecting you. Now, it wasn't smart. Obviously, it just evolved. This is something that just evolved. So this is the kind of thing that we see with most of these organisms. They are just random mutations over time. Obviously, if you believe in a higher power, you could say, well, this is a scourge sent from whoever you believe in. But I don't think about it that way. I think about this is natural mutation. And how do we understand that so we can prevent the next bad natural mutation?

14:00Great. And that leads me to my final kind of ground setting question, which is, could you remind us why sometimes we get it once in our life and we never have to think about it again. Sometimes we have to get a series of two or three, and sometimes we have to get it every year or on a regular basis. What determines that? We don't know. But yeah, so I'm telling you, you know, whoever's out there, let's look at AI. I mean, AI, I think, can really help us try to understand this. Of course, we're going to need more than just AI, but the complexities of what it takes to understand all the different molecular biomarkers and how they go into play, we just don't know.

14:39And how they interplay in the human side and the virus or bacteria side is very complex and we don't know. I will say that for me as an epidemiologist, and I also have a lab. So I work in the lab and I use my lab to help me understand my epidemiologic research. And not the other way around. My epi doesn't inform my lab. It's the other way around. So I take viral samples. I take blood samples from kids from all over the world after different diseases or after vaccination. One of the things I try to understand is associations, right? What is associated with what? I can't prove any of these things.

15:18That's not the kind of lab I have. But I can show that a particular set of vaccines is associated with this kind of outcome. And that's very blunt, a blunt, broad way to do it. But that's how we do it now. So we can, for example, the easiest way to look at these diseases is to go back in time. I teach a history, a class on the history of pandemics, and you can just see over 22 ,000, 3 ,000 years, what has infected us over time. And you get a sense of what disease will do what. Like we, you know, a classic example is smallpox. Again, I hate to come back to that one, but it's just easy. when Edward Jenner realized that cow maids, milk maids, did not get smallpox.

16:07They just, when you have a whole population dying and one group of people is not dying or not even getting infected, you have to figure that out. That's an epidemiologic question. What's different about that person? Well, there's nothing different about them. It's the fact that they were milking cows that had cowpox and they would get cowpox leashes. Now, cowpox and smallpox are not the same virus. They're cousins, but they're not in the same species. They're not the same virus. And so this was providing cross-protection. And in his way, he figured that out. But he took a big step. He scraped the udders of cows, inoculated that into a six-year-old boy.

16:49Yeah. Yeah, which is no informed consent, right? And then exposed that child later on to smallpox. And lo and behold, the child did not die, which was probably good for both the boy and for him. Couldn't do that today and shouldn't do that. But again, it's more about associations in the real world and what can we draw inference from so that we can then start to build our hypotheses about why that might happen. Great, great. And then what about this concept of herd immunity? I'm sure it's important to epidemiologists because you guys look at populations and this is a population effect. So can you walk us through what that means?

17:27And do we always see it with infectious agents, or is it a special situation that is required to have it emerge? Yeah, it depends on the type of transmission. So again, organisms adapt to us and to the natural environment. And so depending on routes of transmission, herd immunity may be more or less important. Measles is a perfect example. Measles, as far as we know right now, and I say that now because another virus could show up tomorrow, but it is very contagious. Probably the most infectious agent we know of. TB and chickenpox are the other two. Maybe Ebola, but in a different way. And the reason is that measles can aerosolize into very tiny, less than five micron droplets.

18:14And because they're so small, they come from the lower airway, They're expelled when you breathe or cough. They can sit in the air with Brownian motion for up to two hours. They can sit out there just like you see dust motes in the air. If you walk into a room where somebody has been who had measles, you can get infected even though the person's not there. So it's highly contagious. And so the question then is, how do you prevent transmissions? Well, it turns out a virus like that is going to be much more transmissible because the opportunity to infect people is much broader. But the other thing that you have to take into account is we can see lots and lots of viruses who might be able to do something like that.

18:55But for some reason, they don't affect us the same way. They may not be as infectious to us. There are many, as we talked about at the beginning, there are many organisms. In fact, most organisms out there don't make us sick, but measles does. So that's the other piece of it. Not only does it have to have an effective transmission, but it has to make us sick. When you put those two together, there are formulas that we can come up with and we can calculate what's the risk of this disease. Now, in general, the more you have people in the community who are not susceptible, the less likely this ping pong or this pinball effect is diminished, right?

19:33So you've got this virus randomly moving in a community. If it bounces against the golden shield of immunity, it's not going to affect you and then therefore not spread in that community. So that's basically how herd immunity works. And so the idea of herd immunity is that you don't need, I mean, is this true that you don't need every, you can get protection without vaccination if everybody around you is protected and they create this shield? Is that the general idea? Yeah. And you know, again, it's not a hundred percent, but it's pretty darn close. And the more infectious something is, the more susceptible, the more immune people you need.

20:09So if you have a very low risk, if there's a disease that's not super contagious, you don't need everybody to be immune. You just need so many people. That's why measles is the canary in the coal mine. Because it's so infectious that if you're not vaccinated at a high left level, it's the first disease that's going to show itself. It's just the harbinger of others to come that are less infectious. This is the Future of Everything with Russ Altman. We'll have more with Bonnie Maldonado next.

20:46Welcome back to The Future of Everything. I'm Russ Altman. I'm speaking with Bonnie Maldonado from Stanford University. In the last segment, we discussed the basics of vaccines, how they work, why they work, how they're approved, and stuff like that. In this segment, we get down to the issue of why have they become controversial. Bonnie will give us a really nice understanding of some of those issues and what we can do to improve public trust and acceptance of vaccines so that we don't go back literally to the Middle Ages. Don't forget, after the end of our conversation, we'll move to the future in a minute where I'll ask Bonnie some questions and she'll give me some answers.

21:22Bonnie, in this next segment, I wanted to ask you kind of an obvious question. Why have vaccines become so controversial? You know, there's not one answer to that question. I scratch my head every single day wondering that, But I think if you take the very meta view of this, I have to look at the history of humankind. We are the healthiest, most entitled generation of people that have ever existed. We live better than kings and queens did in the Middle Ages. Now, that's not that the bar was pretty low there, but we are advancing there. If you look at data around child mortality, children up until the middle of the 20th century, the child mortality rate was still 50%.

22:07So it wasn't until the 1920s to 50s that we started to see child mortality drop. We are doing remarkably well. The thing is that we have very short vision. We're looking at yesterday, today, and tomorrow. But overall, we're doing great. We're living longer. We're living healthier, but we're also suffering from effects of all of the great things that we've been able to do. We eat more because we have more food. We don't exercise because we don't have to. And so we're dying of diseases, of lifestyle diseases. And so there's a backlash now. I think people are seeing all of these effects. And then they include, they embrace vaccines in that.

22:48Vaccines must be bad too because they put chemicals in your body. Well, that's generally not true. We're not putting lots of chemicals in people's body, and the things that they get are very safe. But here's the real issue. The real issue is that you have a, and I've seen this time and time again, just in my short-ish career, meaning, you know, when we're talking about millennia, 30 years is a short time. But I have seen a 75 % reduction in child deaths around the world in my time. When I first started doing research, a million children a year were dying from measles. Today, it's about 100 ,000, 90 % reduction.

23:23So I'm still thinking, I still think we're doing a good job. But the point is our doctors haven't seen measles. Our patients don't see measles. If you have mild side effects from the measles vaccine, but you never saw anybody with measles, why would you get the vaccine? It doesn't exist in their mind. So we haven't done a great job of communicating why these things are important. And the fact that these diseases aren't gone, we're just protected. At the same time, there are a lot of influencers out there, social media saying, look, you don't need the vaccine. Just take more of this vitamin or take more of that supplement.

23:59So we're facing colliding messaging. And I think we need to do a better job of communicating and really reminding people that 100 years ago, this country was a developing third world type country where children were dying. 30 % of children under five were still dying in the first five years of life. Imagine seeing that today. That would be unthinkable, but we don't remember that. So I think a lot of it is messaging. Yeah. It reminds me of that old saying about if you don't learn history, then you might be doomed to repeat it. And that would be really terrible. I mean, people do hear about things like infections in the Civil War.

24:40And so there might be some hooks about some famous examples. So let me ask you, is this a global phenomenon? So I'm very aware of this controversy where we live because it's in the news. We hear about it every day, pretty much. Is this happening all over the world or in different flavors or is it not even happening? What do you see globally? Oh, absolutely. It's happening globally. I mean, there is mistrust in big pharma, in these big organizations. There is mistrust in communication. And frankly, people sometimes don't trust their governments. They see that their governments are maybe not telling them the truth about other things.

25:20So why should they believe this? In many cases, I work with the American Academy of Pediatrics. It's a very trusted organization. And in general, when I go around the world talking about vaccines, the pediatric societies within those groups, first of all, They don't represent the government. These are usually nonprofit institutions. They have a lot of trust. And those are the people that can go out. But they also don't have the same bully pulpit that, say, the government might have or other politicians. And so there's definitely a move over the last 20 years. We definitely have seen this reduction in confidence.

25:57Some of it is, yes, some bad products were rolled out in lower developed countries that didn't have access to the better products. And the other thing is that they're also starting to see reductions in deaths. And so they're also saying, I don't need this anymore. I haven't seen that disease. Let me tell you a brief story. When I was, my very first NIH grant, when I was a brand new faculty member, was working with the Mayan population in southern Mexico. And I came in to study polio. I walked in the door. We set up a field trial, a great field trial, published a lot of work there, found out a lot of stuff.