 This is Schneiderman, Dean Bennett. Ladies and gentlemen, it's an honor to be here. I'm very grateful for the invitation and welcome this opportunity to share some thoughts with you. The issue of immunization today is really at the forefront of the interplay between science and public policy. And that's what I hope to talk with you about for the next few minutes. I want to begin with a syllogism that all successful public health programs ultimately rely on a broad societal consensus, whether we're talking about treatment for multi-drug resistant tuberculosis or a needle-sharing program. And the consensus that has supported our US immunization programs is beginning to erode. And I would argue that a public dialogue about the values that underlie the immunization programs is what is needed to sustain the public consensus required to get the full benefit of modern vaccinology to protect the public health. And this is what I'm going to explore with you this evening. Now, it helps to want to begin by acknowledging the bioethicists who have helped me learn a little bit about this along the way from my institution. And the usual disclosures. I have no financial conflicts of interest and will not be discussing any specific products. And finally, the most important disclosure, which is that I am not a bioethicist, but a general pediatrician. So the need to set the stage. And we have these two cavemen. And they say to each other, something's just not right. Our air is clean. Our water is pure. We get plenty of exercise. Everything we eat is organic and free range. And yet nobody lives past 30. So it seems like a good place to start to talk about what immunization has, in fact, accomplished in the last 120 years. The column on your left is the average 20th century annual morbidity from these vaccine-preventable diseases. The middle column are the reported cases in 2007. And the right-hand column is the percent decrease. And you can see, with the exception of Hupenka for pertussis, we have really had an enormous impact on the incidence of these diseases. And while a number of factors have played a role, most would agree that widespread immunization has been the key factor. The number of vaccines that are recommended for children in the United States has increased dramatically since the 1990s due to our better understanding of immunology, molecular biology, and new technology. So until about 1988, we had essentially DTP, MMR, and polio. And since then, first, we started with the hemophilus influenza vaccine, which was the first of the conjugate vaccines, where a protein was conjugated to a polysaccharide, which then made it possible to immunize very young children against a disease whose morbidity was equivalent to that of polio every year, although largely unknown to most of the public. And what is remarkable are that that disease is essentially gone, very unusual to see a case of hemophilus influenza be meningitis today. But the number of vaccines that are recommended is now relatively large compared to where we were. In 2000, about one-fifth of parents had concerns about the safety of immunizations. Within about four years, most practicing clinicians, who saw children, had experienced a parent who refused a vaccine. Today, instead of 20% being concerned, we are up to 20% of parents actually refusing or delaying some vaccines. And a study that was done to publish just this year gives you a fairly good cross-section of where we are as a nation. Overall, there is strong support for immunization. The great majority of people support immunization, 72%. But we have a growing minority who have serious concerns about immunization. And they manifest that either by expressing their uncertainty or by acting on it and delaying some immunizations or refusing some. Now, some of the things that make this concerning is that compared to parents who accept vaccines, those who refuse them are, in general, older, better educated, and not members of minority groups. And when you look at what their concerns are, they're concerned about vaccine safety. They're concerned that the vaccine itself may cause harm, that it will overload the immune system, and we'll talk more about that later. And they would argue that their children are really not at risk for those diseases or that the diseases themselves are no longer dangerous. What are parents today concerned about? I don't know if this is the right list, but speaking with my pediatric colleagues, we thought this was a pretty good list of what a young parent today would be worried about. And you'll notice that what's missing from that list is any vaccine preventable disease. Were you going to draw this list in 1950? Polio would have been on top of the list. So some things have really changed. Now, what I'd like to do is to briefly explore some of the factors that I think have contributed to immunization hesitancy. Now, first is the decline in vaccine preventable diseases. Again, polio, measles, much less diphtheria, are not part of our cultural experience as a society today. I think also there has been broad recognition, particularly since about the 60s, about the limits of medicine and technology. Has this nation emerged from the Second World War? We had a view that modern technology could pretty much fix anything. It was the primacy of the engineer. And I think little by little we have learned that many of the major concerns of life are not easily solved by medicine and technology. And this, I think in part, explains some of the resurgence of complementary and alternative medicines as people look for other ways to solve problems that they face. There's been a broad growth of consumerism which affects our entire society. And then there are major failures of the US health care system. And here I would point specifically to our failure to deal with mental health and behavioral disorders, autism being among them. Concomitant with that has been a new growth of the Vaccine Injury Compensation Fund, which was a fund created in roughly mid-1980s to compensate people who had been thought to have been injured by a vaccine appropriately manufactured and administered. And that's funded by a tax on every dose of vaccine. Well, that fund, which cannot be used for anything but compensating for injury, is now over $3 billion. And it's no surprise that individuals whose family members have conditions that are not taken care of by our health care system might look to that fund as a way of getting some resources. But there's more, because the origins are complex. Clearly, there has been today a distortion of the scientific process of proposing a hypothesis, testing it, accepting it, or rejecting it, and then refining it. Today, hypotheses are regularly vetted first in the media. And then they are validated by repetition. And when you look for the enemy here, the enemy is us, because I think every major medical journal today releases its findings first to the press, and then those of us who work in clinical medicine often hear about it first on The Today Show or for myself on NPR. Excuse me, going in the wrong direction. Then the issue of causality. And the criteria for establishing causality differs in the world of science or medicine, in the legal world, and in the world of public opinion. And the quickest and simplest example of that is breast implants. Do breast implants cause chronic disease? There is no credible scientific evidence that they do. However, the manufacturers were found libel in a court of law, and clearly they were found guilty or responsible in the court of public opinion. Risk communication is a very complicated art, and case reports are enormously powerful. No matter what the study shows, when you see a parent with a child suffering from a disease or a bad condition, and whose parents believe that that was related to vaccines, that is very, very powerful and often much easier to understand than, for example, an Institute of Medicine report. And today, the media is interested in controversy, and that's what sells. The media's concept of balance is to present both sides of a story. I always like this little piece from the Scientific American. Good journalism values balance above all else. We owe it to our readers to present everybody's ideas equally. If politicians or special interest groups say things that are untrue or misleading, our duty as journalists is to quote them without comment or contradiction. To do otherwise would be elitist and wrong. And then you might notice the date that that appeared in the Scientific American. April 1st, for those of you who can't read, that was a joke. But to make the point, the media do regard balance as evidence of journalistic integrity. They tend to equate one expert with another. And again, their focus is mostly on controversy rather than necessarily a search for truth. Now, not all these names on this slide may be familiar to you, but I would submit that those on the right are highly qualified experts or a website that tries to present strictly science-based information, whereas some of the folks on the left have particular viewpoints and are very effective communicators. And today, communication tends to trump science. And in part, that's because in general, parents do not have a clear idea how to evaluate the credibility of a source of information about immunization. It's not something that they're knowledgeable about, and they really don't know how to go about figuring out who to believe. Now, I'm going to shift and talk now a bit about the history of compulsion for immunization. In both Massachusetts and in England, laws were passed right at the beginning of the 19th century, requiring populations to be vaccinated against smallpox. And interestingly, I just learned on the plane here today that it was about, I think, in the 1890s that the British first dealt with the issue of objections to immunization, and that's where our term conscientious objector comes from. It actually comes from issues around immunization in England in 1890. Well, we were dealing with the same issues here, and the famous case is Jacobson versus Massachusetts. And in that case, Jacobson argued that he had a right to care for his own body as he thought best. And this case, he lived in Cambridge, Massachusetts, and did not want to be immunized against smallpox. And this case went all the way to the Supreme Court, where Justice Harlan wrote in a famous opinion that no one in our society has an absolute right to be solely free from constraint and that society could not exist without constraints. But the constraint had to be based on the necessity of the case and not to exceed what was reasonably required to ensure the safety of the public, and that the compulsory measure should not pose a health risk to the subject and shouldn't be arbitrary or oppressive. Well, that looks very clear, but there's some words in there that require interpretation. What is required for the safety of the public and not pose a health risk to the subject. Now, John Stuart Mill is usually cited as the source of what today we're for having well articulated what we call today the harm principle. And that says that the only purpose for which power can rightfully be exercised over another member of the community is to prevent harm to others. That doing it for their own good is not sufficient. So this then leads us to the fundamental questions that we're going to be talking about for the rest of the afternoon evening, which is when is it justifiable to restrict individual freedom by requiring immunization? And there are a series of steps that most people would argue. When the action or inaction places another individual at substantial risk of serious harm and to protect helpless individuals from a significant threat of harm. And again, going back to Justice Harlan, the restriction of freedom must be effective in preventing that harm. And there must be no less restrictive alternative available that would be equally effective. So now let's talk about what constitutes a threat to the public health. I don't think there's much argument about the first line. These are diseases. This is contagion. This is the risk of epidemics. Smallpox, tuberculosis, polio, diphtheria, measles. Most people would see those diseases as posing a significant threat to the public health. For those of you who may have questions about why is measles on that list, remember back in the days when measles was ubiquitous, essentially everyone got measles. And about 1 in 1,000 children ended up dead or with lifelong brain damage. So in the state of Washington, which has 80,000 births a year, that was 80 kids either dead or with lifelong brain damage. And that becomes, over time, a major burden for the state as well as a tragedy for the individuals. So then we have diseases that are less likely to be spread in outbreaks, but still cause major harm. Hemophilus influenza, again, 20,000 cases a year. About 25% of those kids would end up with some residual. Unlike polio, the victims would not be recognizable in the supermarket, but rather in the classroom. Then what about things that just have an adverse effect on children and the state's interest in protecting the next generation? What about car seats, booster seats, where we're trying to protect individuals from harm? And at least since we're dealing with children here, presumably, a principal motivation is protecting the young, the vulnerable. But then we also have other kinds of costs, and motorcycle helmets are a good example. In my own state, in a state legislature, looking at head injuries from motorcycles, passed a helmet law. A couple of years later, the nature of the legislature changed, the law was overturned, and there was a God given right now to drive down the highway with the wind blowing through your hair for those who have hair. But then the advocates for safety went back to the legislature and showed them who paid for head injuries. And it was this state. And we now have a motorcycle helmet law. So I come back to what is a public health problem, where on this continuum lies the interests of public health, and at what point are those interests strong enough to restrict freedom? Then going back to Justice Harlan, recall that he said that the intervention had to be safe. And so I come back to, again, another balance. What disease risk or threat of harm balanced by what assurance of vaccine safety and efficacy justifies a universal recommendation for a vaccine or even stronger, a mandate, a requirement. Now, this is a good point at which for me to point out that safety is relative. It is not absolute. And that in medicine, we can reject but not prove the null hypothesis. In other words, you begin a study by saying there is no association between a vaccine and an adverse event. You then do a study, and if you find evidence of an association, you can reject the null hypothesis because you found evidence. What you can't do is prove the null hypothesis. You can't prove there is no association between an adverse event and a vaccine. So you can't prove absolute safety. Safety is, again, a relative issue. And I would ask you to think for a second about the old rotavirus vaccine that is no longer on the market. It was called a rotor shield. And it was withdrawn from the market about nine years ago. And with the vaccine, if we had a million individuals vaccinated, about 100 got sick, either from the disease or from the side effects of the vaccine. And one died. And the side effects of this vaccine were an intestinal obstruction called interception. Without the vaccine, about 16,000 will get sick. And about 10 will die from the effects of the disease. And the point in this vaccine was then withdrawn from the market as unacceptable in this country. And the point that I'm trying to make here is that if you are culpable for the deaths related to the vaccine, you're also culpable for the deaths that have occurred when you withhold the vaccine. So you are on the horns of the lemma. So we come back to the fundamental question, which is, what should be the balance between the state's duty to protect the public health and the individual's right for free choice? Now let's look at how that plays out. The way we have restricted freedom in this country is through school immunization laws. And the modern origin of school immunization laws is just up the road in Los Angeles when there was a major measles outbreak in the 1970s. There were deaths associated with numerous hospitalizations. And a very courageous county health officer decided to exclude children from school if they did not have proof of immunity. Some 50,000 kids were excluded from school, but most were back in school within a few days. But that was kind of the beginning of the school entry immunization laws. Quickly, multiple states enacted such laws, and some of them enforced them, but not all. And a CDC study back here in 1978 looked at the incidence of measles in those states that enforced the laws versus those that did not. And as you can see, you had a 10-fold difference in the incidence of measles. So in fact, mandates were effective in achieving high levels of immunization and in ending outbreaks of measles. Well, we have had a growth in the number of kids or parents choosing to exempt their children from immunization. And there are important risks that those kids are exposed to. Exemptors are much more likely to get measles and they're more likely to get whooping cough. Perhaps even more important, no vaccine is 100% effective. Some people who get the vaccine are not protected by it, but they assume that they are. And there are also individuals in the community who can't be immunized because of medical conditions. Well, among the vaccine failures, about 11% of vaccinated children actually acquired their measles cases in an outbreak from an exemptor. So exemptors are, in fact, spreaders who imperiled the health of others in the community. Now, let's look at where we are nationally. There are three kinds of exemptions to state immunization laws. Medical exemptions, religious exemptions, and so-called philosophic or personal choice exemptions. And the green states here have those philosophical or personal choice, or if you want to be British or Australian, conscientious objectors. And keep in mind where those states are, as I show you the next slide, which is the rate of immunization exemptions across the country. And just to go back, you can see that it's most of the highest rates of exemptions are in the areas of the country where there are philosophic exemptions allowed. And Washington State, as you may notice, my state leads the nation. Perhaps why I've been focusing on this issue for a bit. This is a map of Washington State that shows the counties. And the colors of red here designate counties that have greater than 5% of kids exempting. And let me just spend one extra second here on why I picked the 5% number. If you have a school in which 95% of the kids are immunized against measles and 5% are not, and measles gets into that school, it will do all it can do, which is pick off all the susceptibles. 5% is a high enough rate of susceptibility to sustain a measles outbreak in a closed environment like a school. So here's where we were in 1999. And the darker red, by the way, is greater than 10% exemptions. And here's where we are today. Now, if you ask me what are the reasons for exemptions, the short answer is I don't know. Our belief, based on some interviews and experience, the belief of people who work in public health in my community, is that the reasons vary in different parts of our state. In some parts of our state, these are people who have major concerns about vaccine safety or have an alternative lifestyle. In other areas of the state, it is individuals who have a civil libertarian view and object to the state requirement irrespective of the medical issues involved. So let's look what has happened to the US. And this is measles cases from last January. And the first thing you should notice by this slide is the cross-hatching. And all of the cross-hatch areas are unimmunized. So the vast majority of the measles cases are occurred in people who were unimmunized. And next, focus on the colors. The orange half are individuals who were unimmunized by choice. They opted out. So half the measles cases, essentially, of last year were due to individuals who had opted out. But much more concerning is this slide. And this slide is a little complicated, so I'm going to go through it somewhat slowly. The red line shows you the total number of important measles cases each year. The blue bars are imported cases. The yellow bars are cases that occurred within the country as a result of importations. So look at the 2008 bar. And what you see is that measles spread to a far greater extent in 2008 than it had in the preceding decade. And how did it spread? It spread among individuals who had exempted themselves from the immunization requirements. So we have the first harbinger of a threat to the public health from exemptors. Now, when you look at school immunization laws and you ask folks, do they agree with them or not, what you will find is, in fact, that most people agree with school entry immunization laws. And in a survey we did, it stated as the obverse, so disagree here means you support school laws. And back then in 2000, 80% essentially, if parents said children should be immunized to attend school. And today, while those numbers may have changed somewhat, there still is general support for school entry immunization. School laws have worked because parents rely on physician recommendations about whether or not to immunize their children. And by and large, physicians have been supportive of both immunization and school entry laws. What's changing is that not all parents rely on physicians' advice today. And there is more heterogeneity, particularly in some areas, on physicians' advice. So now I would like to now go through what I see as our immediate challenges and give you my view of what we need to do as a nation to restore the societal consensus that we need to support immunization. The first is that we need to be prudent about mandates, that we need to have an exemption process that ensures informed decision making, that we need to be much more effective about communication, about immunization, that we have to greatly expand our investment in vaccine safety science, and that we have to engage the public in developing our policies. And I want to explore each of these a bit. Australia has a rather different approach to assuring high immunization. They do not mandate immunizations in Australia. And you can see that they have immunization rates that are roughly comparable to our own. So let's look at children under the age of two. We have mandates about entry into child care, that is licensed child care. In Australia, they have financial rewards for individuals who are immunized. There are two ways they do this. One is through a child care subsidy and that if you're entitled to a child care subsidy, I think everybody gets some child care subsidy and you get a greater payment if your kids are fully immunized. There's a maternal infant health allowance of some sort and you get a bigger check if your child is fully immunized. At school entry, they have no mandates and by and large, those financial rewards apply only to the first couple of years of life. Interestingly, in this country, we have used finances to achieve immunization, but we did it through penalties. A lower rate of Medicaid supplement or not through rewards. So there are other ways to achieve public health objectives than mandates. It's my belief and now this has been manifested in our state that you need to develop a transparent process for mandating immunization. I'm sorry, I don't know if California has dealt with that, but I think mandates have to be applied only to diseases that are indisputable public health importance and that requires defining what is the threat to the public health. If you're mandating tetanus immunization, tetanus is not a communicable disease, you need to be clear as to why you're doing it. Is it because of the state's interest in protecting children or because of the cost of taking care of people who have tetanus? So for some future disease, we do explain the rationale. You don't want to mandate a immunization unless there is broad support within the medical community for use of that vaccine. The rationale has to be transparent and clear, and the process of mandating should engage the public. And the Washington State Board of Health, in fact, has adopted a series of criteria that with which it will approach future vaccines. Decision making about vaccines needs to be informed. We need to monitor exemption rates. When people ask for exemptions, we need to understand their reasons. And the process for exemption should be thoughtful. We need to discourage what we call convenience exemptions, which is check the box, object in order to get your child registered for school. I'm fond of pointing out that in Washington State, two people or two agencies that work for the governor work at cross purposes. The health department wants to get the kids immunized. The office of public instruction wants to get the kids in school. If you can't get in school unless you have immunized, the school doesn't get paid for that pupil. So somehow we need to remove the financial incentive to opt out in order to get the child registered for school. Also, I think we need to avoid imposing what some of my colleagues are in favor of, which is what I call irrelevant hurdles to exemptions, such as having the parent's injection notarized, which I don't think in any way educates about the risks and benefits. And finally, an exemption should be time limited unless it's for an irreversible medical condition so that people will come back and revisit the issue. And where we have widely held erroneous beliefs or perceptions, those should be confronted. And the one I would like to just address very quickly is the concept that multiple vaccines administered simultaneously overwhelm the immune system. And it's relatively easy to point out that that's fallacious. When we were using smallpox vaccine and whole cell pertussis vaccine, the number of immunogenic antigens that we were injecting greatly exceeds all the vaccines that we administer today. Let me go through that one more time. The smallpox virus vaccine has 200 separate immunogenic antigens. The vaccines we're giving today total somewhere around 125. So the actual immune load is actually less. Now, I couldn't come to Southern California without talking about the problem with selective and alternative schedules. Options other than the recommended schedule. One of the principal objections to those schedules are they really undercut the rationale for the universal schedule, which has been carefully worked out to maximize the benefit, both for the individual child and for the community, and to minimize the side effects. Alternate schedules give credence to erroneous beliefs and reinforce unfounded fears. I think they misinform by failing to distinguish between good and bad science. It leaves infants vulnerable by withholding vaccines for the period of when they are most vulnerable to the adverse effects of disease, and it encourages basically free writing or relying on immunizing other people in order to protect your own child. Finally, by spacing out the schedule, you are absolutely increasing the costs of immunizing the community. We have underinvested in vaccine safety science. Questions have arisen and will continue to arise that require resources to answer rapidly that are not in the budgets for vaccine safety. We need to study the factors associated with adverse reactions, including the potential genetic factors. We need to look at the efficacy and safety of vaccines in special populations. What do I mean by special populations? Individuals who have, for example, congenital heart disease, individuals with family histories of certain kinds of disorders. We need to increase the capacity to do large epidemiologic studies, and I'll show in a minute why they need to be large. We need to explore a greater time window after immunization where we look at adverse effects. This is just a quick snapshot of how big a study has to be to look at an adverse reaction. So if you're looking at something that occurs about one in 100,000 times, you need about 300,000 people in your study. So the last rotavirus vaccine that was licensed was tested in 70,000 children prior to license because we were looking for an adverse event into the perception that with the prior vaccine occurred at about one in 10,000. Now onto the issue of risk communication. Risk communication is a complex art, and I'm just touching on it here. We have a number of inbred biases. Two of them that are just the way we are wired intellectually. The omission bias is that it's safer to do nothing than to do something. And I come back to the withdrawal of the rotavirus vaccine where we accepted more deaths rather than be responsible for a death. Compression, we overestimate rare risks and we underestimate common risks. Many of you, I suspect, would never go out on a golf course with an umbrella and a thunderstorm, but you might very well drive to the shopping center without putting on your seatbelt. That's a good example of irrational behavior. Your risks are far greater on the way to the shopping center. And then there's this issue of the credibility of your information source. There's a belief that if you judge, just remember our cavemen at the beginning, that if you eat well and you exercise right, your immune system will be strong and you won't get sick, or that you can protect your child somehow from contagion by what you feed them or how much they exercise. So talking to this audience, it's particularly important to emphasize that while good science is essential, it is not sufficient. It's complex. There's junk science out there. Safety concerns are presented as plausible. And people's concerns are, by and large, often fear-based. And science alone is not sufficient to overcome their fears. You can't just bludgeon them with scientific information. They often lack trust in the integrity of the expert spokesperson. And they have faith in total alternative beliefs. When you deal with issues that are of low concern, expertise is what people look to. They believe you if you're an expert. But if you deal with issues of high concern, what they care about is your compassion, not your expertise. And I love this quote. I just found out it was from Will Rogers. They want to know that you care before they care about what you know. Now, there's a trend in medicine to use something called motivational interviewing, how you make people implement behavioral change. And the point is that styles that promote resistance are styles that are judging, commanding, lecturing, and things that enhance change are a style of communication that's empathetic, non-judgmental, respectful, with an emphasis on choice. Ultimately, it's the parents who must choose. And in the individual encounter, one needs to use styles that enhance the likelihood of change. So within concerned parents, my bottom line is that's where you play softball. But with the intentional misinformers who have books to sell or other interests in, one needs to play hardball. I love this quote by Jonathan Swift. When erroneous information is repeated on a regular basis, it comes to be believed. So we need a national campaign to assist the primaries' physician in carrying out the education of the public about immunization. We need to use modern techniques of social marketing to, in fact, change behavior. It has to be focused on evidence. And the clear intent is to change behavior and to do so by helping parents to make informed choice. Finally, we need to engage the public in developing policy. There are well-developed methods for public engagement. They're only in the last five years beginning to be used broadly by public health. Interestingly, places like the EPA and the Army Corps of Engineers have had a fair amount of experience with them. I think the first major involvement that I'm aware of was where, in fact, the public came up with a rather different set of priorities for limited amounts of vaccine against pandemic flu than did the infectious disease experts. So I would argue that what Larry King and Oprah should be talking about are what's on this slide. They ought to be talking about what are the duties of families, what are the duties of societies, how we get justice, and what is basically the right trade-off between freedom to choose and the responsibilities of living in our society. I started with a cartoon. I like to end with this cartoon when the sheep is saying to the other, sure, I follow the herd, but it's not out of brainless obedience. Mind you, it's out of a deep and abiding respect for the concept of community. I would be remiss if I didn't end this talk by talking about what the future of vaccinology holds, what the potential is for vaccines to improve the public health. There are a whole number of new strategies listed on this slide, and there are individuals in the audience who are far more qualified than I to discuss many of them. But we have a whole new armamentarium of scientific tools which will allow us to develop vaccines against a vast number of infectious diseases that today we have no ability to or very limited ability to prevent. And this is what I think the future will hold as we begin to learn about, as genetics tell us, which individuals are at risk for a specific adverse effect or which individuals are most at risk for the complications of a disease and therefore need to be protected. In 1954, we had the first transistor radio. Last year, we had the iPod shuffle. Look at where electronics has come in that 55-year period. Well, the analogy I want to draw is this. The error of modern vaccinology began in the 1990s with the hemophilus conjugate vaccine. Where could we be in 2064? If we fully exploit its potential to protect the public health.