Why measles is resurging—and the rise of vaccine hesitancy, with Adam Ratner

Adam Ratner: So the measles vaccine was licensed in the US in 1963. It was a scientific triumph, and it’s a story I like telling. It came on the heels, I think it’s important to realize, of the polio vaccine. It leveraged a lot of the knowledge and the technical know-how that we gained from the development of the polio vaccine. So the reason that we were able to make a polio vaccine in the mid-fifties, it was largely due to this group of … John Enders who was an investigator at Harvard, who learned how to culture cells in dishes in a way that they would support viral replication. So mid 1950s, you have this randomized control trial of more than a million kids, is successful. It shows that the vaccine works. We roll out the vaccine to kids across the country. And people were unbelievably excited about that.

Paul Rand: And grateful.

Adam Ratner: Yeah, absolutely. And the technology that enabled that was then applied to the question of measles. Actually, John Enders had started working on measles before he started working on polio and circled back to it after that. And Enders’ lab was the place where the measles vaccine was developed and where the first testing was done.

Paul Rand: Well, we like to think that this vaccine resistance is a newer phenomena post COVID political world we’re living in. But the fact is, even when the vaccine came out, and there was a live vaccine and then an inactivated vaccine, there was a lot of confusion, if that’s the right word, over what to do. And arguably, that could have started some of this early skepticism.

Adam Ratner: So confusion is exactly the right word. So there was the live attenuated vaccine, which is essentially the vaccine that we still use today. And then there was an inactivated vaccine that came out at the same time. When the Surgeon General made the announcement, there was a preference for the live vaccine. But there was also a description of the fact that the live vaccine had more side effects, meaning that more kids got fever and fatigue and stuff for a couple of days after vaccination. And so parents were confused I think, because given the choice between a vaccine that gave half of the kids fever and one that didn’t, you would choose the one that didn’t if they worked equally well, but they didn’t work equally well. And in fact, we no longer use the inactivated measles vaccine because over time, it showed that it did not work as well as the lab attenuated.

Paul Rand: But it was more than just confusion between two vaccines that had U.S. parents skeptical. They had a concern that we still hear today, why bother getting vaccinated if you can gain immunity from getting the virus naturally?

Adam Ratner: Measles can be clinically not so bad, kids don’t feel terrible and they get a rash and they get better. And so there was this dichotomy in how people experienced measles prior to the vaccine, where for wealthy people in wealthy countries, it was a childhood rite of passage. And you hear that even in the language, like the word measly means something smaller and significant. And that’s how people thought of it.

Paul Rand: But that wasn’t the case for every kid, especially in poorer communities with limited access to healthcare.

Adam Ratner: Then you have these more severe cases and often that manifests as pneumonia, and that can be pneumonia either due just to measles virus or often we see bacterial infections that come on top of measles and can cause pneumonia and sepsis if it disseminates. And internationally, especially in low and middle income countries, it was a much worse burden because measles thrives where it’s crowded, where there’s poverty, where there’s malnutrition. And if you looked there, the death rate was much higher. The time at which people got measles in life tended to be earlier and measles is more deadly in younger infants.

Paul Rand: If I recall from your book, it also affects your immune system’s ongoing ability to fight infections and disease.

Adam Ratner: So this is something that we’ve learned relatively recently and I think is just tremendously interesting about measles virus and is unique to it as far as we know. For several years after measles infection, you are more susceptible to other infectious diseases, non-measles infectious diseases. And there was this paradox that people noticed in some of the early vaccine studies where the measles vaccine overperformed, meaning that they calculated the reduction in deaths that they should see in a particular area if they got rid of deaths from measles. And after measles vaccination, you had a reduction in deaths, but it was beyond what was expected just for measles.

Adam Ratner: And the reason was that for a couple of years after measles infection, these kids had been dying at higher rates of diarrheal disease, pneumonia, other things. And the way that that seems to work is that because measles targets these SLAM receptors, the cells that express these receptors are memory B and T cells. So those are the cells that are responsible for immunological memory. So it’s the reason that once you get a particular strain of the flu or once you get a particular strain of some other virus, you have some immunity to it going forward. And measles, not completely, but pretty significantly, wipes that slate clean.

Paul Rand: These SLAM receptors aren’t just responsible for keeping our immunity intact. They also explain why only humans contract and spread measles.

Adam Ratner: Measles is interesting in some ways because it affects only humans and that makes it unlike a lot of other viruses. Measles travels through the air and when you breathe it in, it encounters cells in the airway that have these receptors called SLAM on them. So SLAM has a day job, which is that it’s involved in cell-to-cell signaling among white blood cells, but a protein on measles recognizes SLAM and it enters those cells. The neat thing is that you have this lining of the airway, these epithelial cells that make a border of the airway and measles doesn’t infect those cells when it first comes into your body. It infects the white blood cells that patrol the airway.

Adam Ratner: So it gets inside those using SLAM and then it gets trafficked to lymph nodes where it comes into contact with tons of other cells that have SLAM. And so it amplifies there and then spreads throughout the body before you get a rash. Before it’s really contagious, it traffics back to the lungs and you cough it out and that’s when you’re most contagious. But by the time that happens, you have this enormously high viral load in your body.

Paul Rand: Because measles has this unique biology and ability to target our most precious cells, it’s even more contagious than the flu, polio or COVID. And there’s a metric that epidemiologists use to measure its contagiousness. It’s called R0.

Adam Ratner: R, which is a reproductive number, is a measure of how well a virus spreads or any contagious thing spreads in a population. The R0, the estimate for measles is around 12 to 14. Depends on how you do the calculations, which population you’re in, et cetera. The estimate for COVID also varies. It depends on when in the pandemic people were making the estimates, but the early estimates were somewhere around two to four. Then you look at something like polio, which is this thing that was very contagious and the people were very worried about until the Salk and Sabin vaccines. That’s about five. Pertussis has an R0 of about somewhere in the neighborhood of 10. So that’s very contagious. But measles really is the king.

Paul Rand: The development of the measles vaccine was a huge breakthrough for public health, but scientists quickly realized they could bundle up the measles vaccine with other vaccines from mumps and rubella. So they created what we know today as the MMR vaccine, a staple of American life for school-age kids.

What is the MMR vaccine?

Adam Ratner: The reason that that particular combination vaccine came about was one of the issues with measles vaccine uptake early on was that unlike with the polio vaccine, the licensure of measles vaccine didn’t come with the way to pay for it. And so individual families were supposed to shell out the money to pay for vaccines. So you’ve automatically at that point, you have accentuated inequity, because richer families are going to do it and poorer families are less likely to be able to do it. There was then some more governmental support for measles vaccine, which is great. It got bundled into some of the same programs along with polio vaccine.

Adam Ratner: Then in the late sixties, there was a vaccine for rubella licensed, and that was really important. We had had a big rubella outbreak in the United States in the years prior to that. And then for many places in the U.S., there was a choice. Are we going to funnel money away from the measles vaccine and into providing support for the rubella vaccine? It wasn’t just something where it was going to get added on. And measles vaccination rates started to drop again because places made that choice. And the idea was A, it also cuts down on the number of shots that an individual kid needs. But B, bundling these things together makes it so that you don’t have these competing priorities.

Paul Rand: The MMR vaccine became part of the U.S. vaccine schedule in 1971. And today, the MMR vaccine is required if you send your kids to school in the majority of schools across the U.S. But now schools are faced with a growing problem, parents who are choosing not to vaccinate their kids against standard diseases. Ratner explains why vaccine hesitancy is growing and what we can do to reverse it. That’s after the break. If you’re enjoying the discussions that we’re having on this program, there’s another University of Chicago podcast network show that you should check out. It’s called The Pie. Economists are always talking about the pie, how it grows and shrinks, how it’s sliced, and who gets the biggest share. Join veteran NPR host, Tess Vigeland, as she talks with leading economists about their cutting edge research and key events of the day. Hear how the economic pie is at the heart of issues like the aftermath of a global pandemic, jobs, energy policy and much more.

Paul Rand: So let’s go back and you’ve obviously spent a lot of time thinking about this. Can you trace this decline in vaccinations rates back to any really benchmark areas or developments, that you look back and say, “This is when it really caught hold”?

Is there a link between vaccines and autism?

Adam Ratner: I think there’s been vaccine hesitancy and vaccine skepticism, as I said, for as long as there’ve been vaccines. And it is fully reasonable for parents to ask questions about any medicine or any treatment that their child is receiving. We hold vaccines to a really high standard because they’re something that is given to essentially the whole population and they’re given to people who are well. You tolerate different side effects in cancer chemotherapy, for example, than you would trying to prevent a disease. So the idea that people ask questions about vaccines goes back a long way, and that is fully reasonable. I think the issue was never that people raised concerns about vaccines. There was the watershed moment of the Andrew Wakefield study in the nineties, where he had a fraudulent and unethical study that purportedly linked the measles vaccine to autism. This study has been debunked in many, many ways. Many follow-up studies have shown no link whatsoever between any vaccine and autism, but certainly not between MMR and autism.

Paul Rand: But that concern persists.

Adam Ratner: Yes, it is sticky, as some people would call it. That concern persists, in part because it is a simple explanation for something that medicine in general doesn’t have a simple explanation for. And that may be because there is no one simple explanation for it. I have a mentor, Paul Offit, who says it’s much easier to scare someone than it is to unscare them. Again, many, many studies … And many studies now that have looked at early diagnosis of autism, genetic diagnoses of autism, things that precede receipt of the MMR vaccine, that would make it to the MMR vaccine, could not possibly have caused it. But even in the face of all of that, there’s not a three-word explanation for autism like vaccines cause autism, that science will likely ever be able to give. And that is a disadvantage.

Paul Rand: Well, one of the arguments that comes up of people that have chosen not to vaccinate themselves or their children is, “Well, that’s a personal choice.” And you’re making the case that it’s not really a personal choice because is of the extraordinary, really, ability for this disease to infect so many other people. It is a community choice. And it really isn’t hypothetical if you look back to 2019 in New York.

Adam Ratner: Yeah, it certainly didn’t feel hypothetical at that point.

Tape: The national measles outbreak keeps growing. 333 cases have been confirmed this year in 15 states. The largest outbreak is in Rockland County, New York.

Adam Ratner: There was a outbreak that took place in two places. In New York City where most of the cases were, and then in Rockland County.

Tape: So measles outbreak in New York City has been declared a public health emergency. The outbreak centers on a community in Brooklyn where more than 250 people have gotten measles since September.

Adam Ratner: And we had between six and 700 cases in New York. The initial cases were seeded by an unvaccinated person returning from international travel, which is often how it goes. And the reason that there was sustained spread was that within a relatively cloistered community, there was a much lower rate of vaccination than we needed to prevent measles spread.

Tape: Mayor Bill de Blasio has ordered mandatory vaccinations. People who don’t comply could face a fine of up to a thousand dollars. Officials are blaming the outbreak on anti-vaxxers who are spreading false information.

Adam Ratner: So in the city as a whole, if you just looked at the statistics for New York City in 2018, somewhere between 95 and 98% of kindergartners had their MMR vaccines up to date. So they were immune to measles. But the problem is that rates at the level of cities or counties or states, can miss pockets of undervaccination. So in this case, the community in which that child returned to, had about a 60 or 70% MMR vaccination rate, and that is enough for measles to spread and to pick up speed. The story of that outbreak goes back a decade or two prior where that’s a community that used to have high rates of vaccination and over time, due to a number of issues, there was specific targeting of the community by the anti-vaccine group and an erosion of trust in public health.

How long does the measles vaccine last​?

Paul Rand: Even with really high vaccination rates, there’s always going to be the slight risk of an outlier. And a lot of vaccines, including the measles vaccine, aren’t a hundred percent perfect at immunizing everyone.

Adam Ratner: There’s a primary vaccine failure rate for the measles vaccine of about 5%. And if you get two doses, that’s about 3%. Meaning that if you appropriately vaccinate a hundred people, you have three of them who are still susceptible to measles. If you vaccinate everybody, that’s fine. That’s not enough people to have measles continue to spread in the population. But if you have a lot of people opting out and you have that situation where not everybody is protected … And you have people who can’t get the vaccine. We don’t give it until about a year of age, first of all. So everyone under a year is susceptible. And then you have kids who are adults who are getting chemotherapy or who’ve had an organ transplant or something like that. The measles vaccine is a live attenuated vaccine that we don’t give to immunocompromised people. And so there’s this built-in susceptible population that you can’t avoid. And the way that we avoid that is by vaccinating as much of the population as we can.

Paul Rand: Okay. And there is the perception that if you’ve been vaccinated or you’ve had measles, you’re likely not to get it again. But the question that really starts coming up, and I think the New York Times just ran an article recently that really talked about adults being of higher risk for developing diseases, because vaccinations have gone down. So this really is … Again, if somebody’s being by the fact, “Well, I’ve had the vaccine,” that really shouldn’t provide that much comfort.

Adam Ratner: Yeah, I think that most people who are appropriately vaccinated have lifelong immunity against measles. And it’s not a hundred percent true for measles. Like measles immunity can wane.

Paul Rand: These outlier cases of vaccine failures, or protection warning, have been used as talking points by vaccine skeptics. And we saw the same talking points used about the COVID vaccine, when people learned that the vaccine didn’t stop you from getting infected.

Adam Ratner: The messaging was not ideal for many of these things, and people gave different messages over time because things changed quickly. I think there was such relief when the initial studies of the mRNA vaccines came out, when it looked like they protect beautifully against death and hospitalization, which they do, and they provide short-term protection against acquisition of infection, which is also true and still true. I think we didn’t know at that point whether people would need to be boosted. I think we didn’t know the extent to which there would be variability of the virus over time. And some of it was public health, people’s failure to communicate those things. Some of it was that people tried to communicate those things and they weren’t heard.

Adam Ratner: I think that the side effect thing is in maybe in a more nuanced way, also a triumph, though. The rare but significant side effects, so I’m talking about myocarditis after the mRNA vaccine or clots after the adenovirus vector vaccine, the Johnson Johnson, those are real but rare side effects. Those are things that were detected in post-licensure surveillance. I think the risk-benefit still favors certainly for the mRNA vaccine, and arguably, if it were the only choice, for the adenovirus vaccine as well. The risk-benefit in the middle of a pandemic would still favor getting those vaccines. Your odds of getting COVID and getting myocarditis from COVID far exceed your odds of getting myocarditis from the COVID vaccine. And I think that kind of messaging was lost.

Paul Rand: While many side effects are rare, there is still no guarantee that any vaccine is a hundred percent safe. That’s why in 1986, then President Ronald Reagan signed into law the National Vaccine Injury Compensation Program.