MANDATORY VACCINATION: WHY WE STILL GOT TO GET FOLKS TO TAKE THEIR SHOTS
Class of 2006
April 27, 2006
This paper is submitted in satisfaction of the Food and Drug Law course paper and the Harvard Law School 3L Written Work Requirement
Vaccination is widely considered one of the greatest medical achievements of modern civilization. Childhood diseases that were commonplace less than a generation ago are now increasingly rare because of vaccines. In order to be effective at eliminating communicable diseases, vaccines must be administered to sufficient levels of persons in the community. Because of this, public health officials have mandated vaccination for certain diseases as a condition to school attendance. The overwhelming effectiveness of vaccination programs may lead individuals to ignore the benefits of vaccination and focus more on the risk of side effects. Moreover, some have criticized the coercive nature of these programs. These objections may lead to an unacceptably high number of exemptions, which can compromise vaccination programs and leave the population susceptible to outbreaks.
This paper explores vaccination programs with an eye toward greater public safety without ignoring the reality of a small but committed group of vaccine critics. The paper begins with a discussion of the historical development of mandatory vaccination policies and the issues posed by exemptions. It then addresses some of these issues in the context of vaccine safety. It also seeks solution by framing the discussion in economic terms. It concludes by recommending stricter enforcement of mandatory requirements for most vaccines and greater dissemination of information on the continued importance of vaccination.
TABLE OF CONTENTS
Vaccination is widely considered one of the greatest medical achievements of modern civilization. Childhood diseases that were commonplace less than a generation ago are now increasingly rare because of vaccines. The smallpox vaccine has eradicated a disease that was responsible for centuries of outbreaks and had a 30% fatality rate. Physical handicaps resulting from polio can still be observed on some of those who were children before Jonas Salk developed a vaccine in 1955. Formerly common childhood diseases are now rarely observed. Even ear infections may soon be prevented by vaccination. The widespread success of vaccinations has led one medical report to comment that “[n]ext to clean water, no single intervention has had so profound an effect on reducing mortality from childhood diseases as has the widespread introduction of vaccines.”
The story of modern vaccination begins with Edward Jenner’s development of the vaccine for smallpox, one of the most feared diseases in recent history. At first, vaccination was optional and not everyone chose to vaccinate. In time, states would allow municipalities to mandate vaccination in time of outbreak in order to protect the public from epidemics. A further step was taken when states imposed smallpox vaccination as a prerequisite for attending public schools. These requirements were amended in time as new vaccines were developed. At some point actual outbreaks and epidemics ceased to be the trigger for mandatory vaccination, and prevention became the overriding justification. Most states today require vaccination for a multitude of childhood diseases, including measles, diphtheria, pertussis, polio, and now even chickenpox.
Because of the success and the mandatory nature of vaccination, most people would probably not consider vaccination an optional method of medical treatment. For most parents, the “decision” to vaccinate is equivalent to the “decision” to feed one’s child. Typically, a doctor informs parents of the school vaccination schedule and the parents consent to having their child vaccinated. Since the vaccination schedule usually corresponds to the scheduled doctor visits for infants, full compliance with mandatory vaccination schedules is typically not a problem and can usually be substantially accomplished by age two.
For some parents, however, vaccination is no routine matter. From the time of Jenner’s smallpox vaccine, vaccination has had its critics. In the two centuries since that time, many different types of objections have been raised. Some have questioned the scientific qualifications of mass immunization. Others have focused on the personal liberty interests at stake and have objected to the paternalistic nature of government imposition of what is viewed as a personal medical choice. Still others have opposed vaccination for personal or religious reasons.
Today, some parents raise similar objections. The idea that a potentially harmful substance is being placed directly into the bloodstream raises a red flag for some. Additionally, the decline of many diseases for which vaccination is still mandated may make some parents skeptical of the continued wisdom of subjecting a child to a vaccine, even if the vaccine is considered extremely safe. This skepticism grows when some point to the correlation between vaccinations and conditions such as SIDS and autism. Whether or not such a correlation is scientifically significant, many parents simply wonder if it is wise to vaccinate against a disease unlikely to afflict their child if any chance exists that the vaccine will cause autism, SIDS, or any other side effect.
Since the efficacy of a particular vaccine corresponds directly with the percentage of a given population that has been vaccinated, proponents of mandatory vaccination have sought to convince those with reservations about vaccines that vaccination is the right choice. The Center for Disease Control has attempted to allay possible reservations parents may have with vaccinations by rebutting some of the commonly held fears about vaccines. The CDC has pointed out, for example, that most adverse effects from vaccines are “minor and temporary, such as a sore arm or mild fever.” Because vaccination often involves the introduction of a harmful live (although seriously weakened) organism into the patient, vaccination can never be 100% safe. Serious side effects usually occur only between one per thousands to one per millions of doses, while some serious reactions and death occur so rarely that accurate risk assessment is difficult. The CDC has also responded to many of the other concerns raised about the need for vaccination, and the FDA continually works to ensure vaccine safety and efficacy, but many still harbor reservations toward vaccination.
This paper will endeavor to discuss some of the most common objections to vaccination programs in general while trying to shed light on the veracity and tenability of these objections. Part I will discuss the nature of mandatory vaccination programs in this country; both scientific and historical issues will play a key part in this discussion. Part II will describe the role of the FDA and other governmental bodies in the overall vaccination picture. Part III will attempt to utilize multiple analytical tools in search of possible solutions to the dangers posed by those who may attempt to opt out of vaccination programs. It will first examine vaccination through the lens of an old television show episode. It will then adopt an economic analytical framework to discuss the balance between individual and general welfare in the context of vaccination. Part IV will conclude with some observations on how the goal of greater public health might be achieved without completely neglecting the concerns of many in the community regarding the prudence of using a medical technique that by definition relies on a degree of coercion.
I. MANDATORY VACCINATION
Jenner’s smallpox vaccine led to the research and development of vaccines for other widespread and epidemic diseases. The twentieth century saw the development of vaccines for such diseases as polio, diphtheria, tetanus, pertussis, measles, and others. As with the smallpox vaccine, many of these vaccines soon found their way into vaccination programs mandated by the government, albeit through a somewhat different pathway.
Mandatory smallpox vaccination programs typically arose through state police power legislation authorizing municipalities to deal with outbreaks. Typically, when a local municipality decided that the threat of outbreak was sufficient to exercise this authority it would require vaccination of everyone in the community (with a possible exception for individuals who could demonstrate uncommonly high health risks from receiving the vaccine, although this exception sometimes applied only to children) and fine and/or quarantine those who refused to be vaccinated. When other diseases became preventable by vaccination, outbreak ceased to be the trigger for mandatory vaccination. Rather, because of their cost-efficiency and their ability to reduce and ultimately eliminate disease, vaccination programs became an important part of general public health policy.
Most of the time, vaccination programs are accomplished through the dual efforts of national entities (which tend to develop and recommend vaccines) and state legislatures and local boards of health (which usually implement these recommended vaccines through vaccination programs). It is not entirely accurate to refer to this as “mandatory vaccination,” as typically individual states will not criminally punish parents for not vaccinating their children or forcefully subject individuals to vaccination. Instead, states typically condition school enrollment on proof of vaccination. Though it may be a high price to pay, home schooling is usually an available means parents have if they wish to bypass these vaccination requirements. Moreover, most states grant exemptions to vaccination requirements for religious reasons and some even grant exemptions for philosophical reasons (in addition, every state exempts from school vaccination requirements individuals who cannot be vaccinated for medical reasons).
The connection between school enrollment and vaccination programs may now seem obvious. Public health officials, faced with a means of protecting the general population from the harmful disease smallpox, realized that mass vaccination could lead to a sufficient level of immunity to eliminate the risk of outbreak, even for those in the community unable to vaccinate (because of medical reasons, for instance). Because of the concept of herd immunity, public health officials considering the proper utilization of vaccines were dealing with a medical procedure quite out of the ordinary. Since vaccination itself does not typically provide 100% immunity to a disease, vaccinated individuals can still contract the disease. Yet because of herd immunity, if a sufficient level of vaccination within a population is attained, the entire population will no longer be susceptible to the disease. In this way, vaccination came to be viewed not only as a personal medical choice but also as a step taken to improve the overall health of the population.
With the rise of public schooling in the mid- to late-nineteenth century, cities decided to condition public school attendance on smallpox vaccination. By the latter part of the century, many states had adopted this practice. Such a policy makes sense when one considers the increased risk of infectious disease in public areas like cities in general and schools in particular. By mandating vaccination for school attendance, of course, the state would eventually have ensured the vaccination of the entire population by the time the initially vaccinated generation became the oldest living one.
These vaccination schemes have faced challenges, both legal and social, throughout their existence. The reasons for such challenges have ranged from personal liberty interests to doubts about the efficacy of vaccines. State courts in the nineteenth century typically upheld both the enactment of mandatory vaccination programs and the delegation of power to local authorities. More importantly for the future of mandatory vaccination policy, two important Supreme Court decisions in the early part of the twentieth century affirmed the power of state governments both to mandate vaccination and to delegate a broad degree of authority to local municipalities and health boards to carry out particular vaccination programs.
In 1905 the Court held in Jacobson v. Massachusetts that the general police power of states is broad enough to overcome a Due Process claim brought by an individual who claimed his personal liberty interests were unconstitutionally invaded by the mandatory smallpox vaccination program in question. In an opinion by Justice Harlan, the Court ruled that the constitutional guarantee of liberty “does not import an absolute right in each person, to be, at all times and in all circumstances wholly free from restraint.”
This case still represents the initial constitutional basis of most mandatory vaccination legislation. Many states still provide for the governor or a public health official to mandate vaccination for all in the event of an outbreak. Individuals who cannot vaccinate for health reasons or who refuse to vaccinate may be quarantined in order to protect the population in some states. These laws gained greater relevance following the terrorist attacks of 9/11 and the increased public concerns regarding bioterrorism. For the most part, however, mandatory vaccination laws in the name of outbreak control have given way to vaccination requirements as a prerequisite for school attendance.
The issue of school vaccination came before the Court nearly two decades after Jacobson . In Zucht v. King , the plaintiff challenged a general grant of authority from Texas to local boards of health to condition school entry on proof of vaccination. To differentiate the case from Jacobson , the plaintiff noted that the San Antonio ordinances mandated vaccination even in the absence of evidence of outbreak. The Court, speaking this time through Justice Brandeis, upheld the validity of the ordinances as well as the broad grant of authority to local health boards. On the issue of the state’s power to mandate vaccination, he merely cited Jacobson : “[l]ong before this suit was instituted, Jacobson v. Massachusetts...had settled that it is within the police power of a state to provide for compulsory vaccination.” As for entrusting a broad degree of authority on local health officials, he noted that Jacobson and other cases had affirmed that a state may “delegate to a municipality authority to determine under what conditions health regulations shall become operative.” This delegation includes the permission to vest municipal officials with “broad discretion in matters affecting the application and enforcement of a health law.” In summary, the Court found that these ordinances were valid assignments of “that broad discretion required for the protection of the public health.” The language of the opinion emphasizes the importance of the public health as the key justification for mandatory vaccination.
Zucht , along with Jacobson , thus became the legal foundation for the mandatory vaccination laws of the twentieth century. Modern school vaccination laws and policies have grown from early mandatory smallpox vaccination laws:
The early successes of school vaccination laws against most political, legal, and social challenges helped lay the foundation for modern immunization statutes. Since the introduction of smallpox vaccination policies in the mid-to-late 1800s, states have amended them to include additional diseases as new vaccines become available.
Though various amendments and additions have been made to mandatory vaccination laws throughout their history, the past half century has experienced the true culmination of mandatory vaccination policy. Public health officials have been able to institute a scheme for near-universal vaccination:
Many existing school vaccination laws were enacted in response to the transmission of measles in schools in the 1960s and 1970s. State legislatures at that time were influenced by the significantly lower incidence rates of measles among school children in states that strictly enforced vaccination requirements and school exclusions in outbreak situations without significant community opposition. Rather than having health departments require immunization in emergency conditions, legislatures acted to prevent disease by mandatory immunization as a condition of enrollment or attendance in schools or licensed day care facilities.
Moreover, states have not been completely left to implement the recommended immunization schedule. Though school requirements are still a state matter, national public health officials are typically able to enact their recommendations through federally funded immunization plans. These plans require states to implement and enforce federally recommended immunization requirements before the states can receive federal funds. The current recommended vaccination schedule appears below.
Recommended Childhood and Adolescent Immunization Schedule
Common Name or Symbol
Number of Doses
Birth, 1-2 months, after 24 weeks
Diphtheria and tetanus toxoids and acellular pertussis
2 months, 4 months, 6 months, 15-18 months, 4-6 years, Td booster at age 12 and every 10 years thereafter
Haemophilus influenzae type b conjugate
2 months, 4 months, 12-15 months
2 months, 4 months, 6-18 months, 4-6 years
Measles, mumps, and rubella
Two shots at least four weeks apart beginning at age 12 months
Any time after age 12 months if the child has not had chickenpox
2 months, 4 months, 6 months, 12 months
6 months and annually thereafter for children with certain risk factors
First dose at 12 months, second dose at least 6 months thereafter
Challenges and Concessions
While school vaccination requirements have been credited with bringing about the control and elimination of many devastating childhood diseases, critics have continued to voice concerns and raise legal and political challenges to the entire process of mandatory vaccination.
Personal Liberty Concerns
One key argument against mandatory school vaccination has always focused on government intrusion into what is considered a personal medical choice. Just as the government cannot force a person to have surgery to repair a torn ligament, for example, the government should not be able to force parents to vaccinate their children if the parents believe that vaccination is not the best medical decision. One prominent critic of mandatory vaccination has stated her organization’s goal as simply providing parents with choices: “[w]e believe that health care consumers should have the right to choose the type of preventive health care that they want to use – including choosing whether to use one, ten, or no vaccines.” Other objections along similar bases argue that mandatory vaccination violates the medical ethic of informed consent or even that school district control over mandatory vaccination policies amounts to the unlawful practice of medicine without a license.
The typical counterargument given by the public health officials is to point out that one’s decision to vaccinate, unlike one’s decision whether to undergo surgery, affects the health of others in the community. To allow parents the right to choose not to vaccinate is to infringe on the ability of other parents to raise their children in a society free of certain deadly diseases. From a legal standpoint, Jacobson still seems to have settled the issue that at least under some circumstances, the government may force an individual to receive a vaccination.
Although public health officials have the legal authority to mandate vaccination for the public health under Jacobson, they should be very mindful of the personal liberty concerns just stated. Those with such views often cling to them vigorously. As certain vaccine-preventable diseases decline, such concerns become even stronger. For this reason, it is important for public health officials to support their mandatory vaccination programs with justifiable arguments rather than simply citing legal precedent or historical tradition in support of their exercise of power. Fortunately for public health officials, the benefits provided by vaccination programs can be utilized to justify the existence of such programs.
Safety Accountability Concerns
A variation on the consumer choice challenge to mandatory school vaccination requirements tends to accuse the public health community of conspiring with or at least willfully acquiescing to powerful vaccine manufacturers at the expense of citizens. Mandatory programs, the argument goes, eliminate any accountability from vaccine manufacturers that the free market might otherwise provide. Both the safety and efficacy of vaccines fail to improve because manufacturers do not have to respond to consumer concerns. Mandatory programs thus prevent better vaccines. A prominent critic of these programs has stated that if mandatory vaccination programs are ended, “we will have the ability to put economic pressure on the drug companies and on the health agencies to do a better job with vaccine safety and efficacy.”
The strength of this argument lies in its apparent lack of hostility toward vaccines per se. Given the historical success of vaccination in eradicating smallpox and in reducing or eliminating the risk of other childhood diseases, any critique of mandatory vaccination programs that focuses on the use of vaccines generally is likely to be dismissed by those in the field of public health. By focusing on the economic drawbacks inherent in a mandatory vaccination program and how those drawbacks can negatively affect the quality of vaccines, this argument may gain more traction. Indeed, all sides of this debate claim to desire both safer and more effective vaccines.
The response to this argument, I would imagine, would be to emphasize the drawbacks of opening up the “market” in this case. Because vaccination programs depend on a sufficient percentage of the community being vaccinated, complete consumer choice carries with it problems that might be absent in a standard market. As for vaccine quality, FDA regulation is in place to ensure a sufficient level of safety and efficacy to accomplish the goals of vaccination. The pressure faced by vaccine manufacturers to obtain and maintain FDA approval should provide a check sufficient to guarantee proper vaccine quality. If not, the answer should be to raise FDA standards, rather than to jettison the entire mandatory vaccination process and with it the likelihood of maintaining a sufficient level of immunity among the population.
This response might be unacceptable to those concerned. If the connection between public health officials entrusted with implementing the mandatory vaccination schedule and FDA regulators entrusted with ensuring the safety and efficacy of vaccines is seen as too close, proposing higher FDA standards as a solution may not allay concerns. The independence and integrity of FDA is therefore critical in this arena, just as it is in other areas of public health.
Concern of Unknown Risks
In what may be a combination of the two challenges previously discussed, many individuals challenge vaccine programs because of a lack of information about vaccines. Many people, for example, legitimately question the wisdom of forced vaccination before long-term effects of a vaccine are studied. One website that purports “to provide a wide range of news and views on vaccination and vaccination policy” has summarized this challenge to vaccines simply as opposing the idea of “a parent, any parent, being forced to do something that has even a remote chance of harming their child.” Since long-term (ten or more years down the road) and low-risk (on the order of one-per-million or less, for example) side effects may truly be unknown, this concern does present a challenge for public health officials.
Unfortunately, even the best studies are unable to fully determine all long-term consequences of vaccination. In addition, “[t]here is no such thing as a ‘perfect’ vaccine which protects everyone who receives it AND is entirely safe for everyone.” Therefore, it is true that mandatory vaccination probably forces some parents to inject their children with a substance that will cause some unknown harm.
As with the other objections to mandatory vaccination, however, this objection suffers from a critical flaw. Mandatory school vaccination requirements are not justified solely on the benefit they provide to the recipient. Instead, it is the benefit they provide to the community as a whole by ensuring a sufficient level of vaccination to prevent outbreak that justifies their intrusive nature on individual medical decision-making. For this reason, if public health officials did not enact the mandatory vaccination program, they would be forcing on parents a system that had at least a “remote chance of harming their child.” Because the decision to enact a community-wide vaccination program must be made at the general level if it is to be made at all, and because some children will undoubtedly suffer some health consequences regardless of which policy is chosen, individuals will always be able to raise this argument against mandatory vaccination programs.
A better critique of these programs would focus on whether mandatory vaccination causes more overall harm than a voluntary system; that is, is it better when viewed at the general, rather than the individual, level? Ironically, the very success of vaccination programs in reducing the incidence of once-prominent diseases has led some to ignore the overall and continuing benefit of community vaccination (herd immunity). But for parents to decry the “remote chance” of harm from vaccination while ignoring the very real chance of outbreak in an under-vaccinated population is to reframe the issue entirely.
Other challenges to vaccination laws have cited strongly held religious or philosophical positions against vaccination in general. Such challenges require a different type of response from public health officials; often the options are limited to overriding such objections and excluding children of parents adhering to such positions from public schools (which is constitutionally permissible under Jacobson and its progeny) or creating exemptions to vaccination requirements (which is detrimental to the overall goals of mandatory vaccination if a sufficient number of exemptors exist). Reactions to such religious and philosophical concerns vary from state to state, with a general trend toward greater accommodation of objectors.
In response to these and other challenges to mandatory vaccination laws, states have enacted various exemptions to vaccination requirements for school entry. Actual enforcement varies by state.
All states provide exemptions for those with medical risks associated with vaccines. If certain contraindications indicate a likelihood of harm from a particular vaccine, the exemption will be allowed. Because such cases are rare and exemptions relatively easy to enforce, there usually is very little risk of compromising the efficacy of the overall vaccination program by granting these exemptions. The ability to grant medical exemptions while still maintaining sufficient levels of vaccination to provide community-wide immunity is one of the great accomplishments of the vaccination system.
In addition to medical exemptions, almost every state grants religious exemptions for those with sincere religious beliefs opposing vaccination. Individual states tend to vary with regard to the level of religious conviction necessary to obtain a religious exemption. Such exemptions reflect the sometimes uneasy balance between mandatory vaccination programs and First Amendment Free Exercise rights, even though the Supreme Court has validated the right of states to mandate vaccination without providing for such exemptions. West Virginia, for example, does not provide religious exemptions.
Some religious exemption statutes have spurred challenges on Establishment Clause grounds by those who claim they favor organized or recognized religions over the sincerely held religious views of others. These challenges, if successful, would lead to the invalidation of many religious exemption statutes. Rather than decrease the number of religious exemptors, however, this may actually lead to more religious exemptors. The political climate of our day, along with the experience of a few states already (such as Arkansas), suggests that legislatures may respond to invalidation of religious exemption statutes that require adherence to an organized religion by drafting more general and expansive religious exemption statutes. By subjugating religion to compulsory vaccination, courts may actually be helping to bring about a system with even more religious exemptors, thereby harming the very vaccination programs to which religious objections had been subordinated.
The possibility that some parents who strongly oppose vaccination for other than religious reasons has led to other means of exempting from mandatory vaccination programs. In some states, people may avoid vaccination requirements by way of philosophical exemptions. In California, for example, a parent need only “submit a letter or affidavit stating that the immunization is contrary to his or her beliefs” to exempt their child from vaccination requirements. “Where available, parents are taking advantage of such exemptions with growing regularity; and in states offering both exemptions, the number of philosophical exemptions far exceeds the number of religious and medical exemptions.”
States without philosophical exemptions, moreover, are often lax with their enforcement of religious exemptions. Because of this, parents in these states can usually submit insincere affidavits purporting to object to vaccination for religious reasons and local health officials, unconcerned with delving into the sincerity of such affidavits, will widely grant exemptions. In most states, therefore, persistent parents can usually find some way to exempt their children from vaccination requirements. If all else fails and vaccination is still regarded as unacceptable to the parent, the option of home schooling may provide a final avenue of evading these school vaccination requirements.
Dangers of Widespread Exemptions
The ease with which non-medical exemptions can typically be obtained has raised concerns among many that the benefits of widespread immunization are being compromised. Because of the nature of medical exemptions, unvaccinated persons in a community with only medical exemptions would be expected to be few and dispersed. Herd immunity can be attained, and protection is ensured for both the vaccinated majority and the unvaccinated few. Broadly granted philosophical and religious exemptions make herd immunity more difficult to attain and increase the risk to the community. This risk is exacerbated by the fact that many of those who apply for such exemptions “will cluster together in one geographic area.” This cluster effect tends to increase the likelihood of serious outbreaks:
Recent studies have shown that clusters of exemptors, who are significantly more susceptible to contracting vaccine preventable illnesses, pose an increased risk of spread of diseases not only to their unimmunized peers, but also to the surrounding, largely vaccinated population.
Given that many childhood diseases seem to be in decline, exemptors may fail to realize the continued value of vaccination. As the mumps outbreak in Iowa makes clear, however, vaccination programs take time and are at risk if vaccination rates fall. Other diseases are still prevalent in other parts of the world, and outbreaks can still occur in this country due to the prevalence of international travel. Ever though measles is rarely observed in the US, for example, the World Health Organization has reported that nearly 900,000 measles-related deaths occurred in developing countries in 1999. Until diseases are eradicated globally, it may be necessary to continue vaccination.
Because many of the aforementioned risks are frequently underappreciated by those who seek exemptions, some have suggested a combination of stricter enforcement of exemption requirements and increased public knowledge of the reasons underlying childhood vaccination requirements. Knowledge is indeed essential to the resolution of this problem. The easier it is to obtain an exemption, the less likely individuals are to understand and appreciate the importance of widespread participation to the success of a vaccination program. Greater public appreciation of the need for such participation (even for diseases that seem to be in retreat), along with greater information on the safety of vaccines can go a long way toward increasing public health in this area.
Partial Exemptors – A Modern Phenomenon
The availability of exemptions has led to other interesting developments in the vaccination debate. Recently, for example, challenges have been raised against the need for mandatory chickenpox and hepatitis B vaccines. Diseases such as these, which are either not greatly feared (chickenpox) or transmitted primarily through voluntary rather than involuntary contact (hepatitis B), do not fit neatly into the typical justification for mandatory vaccination. Nevertheless, public health officials have decided that recently-developed vaccines for these diseases should be placed on the recommended schedule. This has given rise to a significant number of partial exemptors – those who are not opposed to vaccination requirements per se, but who oppose particular vaccines on the schedule. Such a position may not have been comprehended by those who drafted the religious and philosophical exemptions, which seem to assume that a parent’s opposition is to vaccination generally, rather than to a specific vaccine.
Because the religious exemption is usually constructed to apply to those who oppose vaccination generally because of sincere religious beliefs, would-be partial exemptors have difficulty fulfilling their optimal desires. In states without a philosophical objection, parents must choose either to accept the entirety of the recommended schedule of vaccines or to obtain a religious exemption for all vaccinations. Parents who live in states with a philosophical exemption are much more able to tailor their objection to those vaccines with which they disagree.
From the standpoint of a public health official, this presents two possible worlds. In the world with traditional religious exemptors but no philosophical exemptors, overall percentages of vaccinations would be relatively equal from vaccine to vaccine, and higher vaccination rates would be obtained for diseases associated with more objectionable vaccines at the expense of lower vaccination rates for diseases associated with less objectionable vaccines. By contrast, in the world with philosophical exemptors, the public health official would observe higher vaccination rates for the less objectionable vaccines and lower vaccination rates for the more objectionable vaccines.
The difference between these two worlds can have far-reaching implications. If parents are forced to make the all-or-nothing choice, a significant enough number could choose to forego vaccines (including some which they would otherwise accept) that herd immunity is lost, even for less objectionable vaccinations. On the other hand, a significant enough number could accept the more objectionable vaccinations to bring about herd immunity for those diseases. Though the public health official might prefer a world in which neither religious nor philosophical exemptions exist, such a world may not be possible. Therefore, the official should determine which of the two possible worlds provides a greater overall level of safety for the society. In addition, potential public reaction to a vaccine should cause the public health official to consider the ramifications the addition of a vaccine to the schedule will have on those vaccines already on the schedule.
Because partial exemptors have the potential to sway the balance between herd immunity and vulnerability, public health officials must take account of their concerns. Unlike in years past, today the development of a new vaccine presents public health officials with a choice that can affect other vaccines on the recommended schedule. Though the possibility for a chickenpox- and Hepatitis-B-free nation may seem tempting, officials should now consider the possible consequences of mandating such “borderline” vaccines. Parents who might otherwise vaccinate according to the old schedule might have second thoughts about the new vaccines on the schedule and seek means of avoiding the new requirements. If no means exist for avoiding the new vaccines other than complete exemption on religious grounds, parents who would subsequently pursue such exemptions would bring about a lower level of immunization for older diseases.
Studies may be necessary in the above situation to determine whether herd immunity status could be in jeopardy for those diseases for which vaccines are already on the schedule. While one solution might be to provide parents with greater ability to tailor their individual vaccination desires, such a solution would undermine the efficacy of newly scheduled vaccines. In addition, greater levels of flexibility in vaccination choice would undermine public understanding of the community-based nature of vaccination. I think it might be worth sacrificing the efficacy of the newer vaccines in order to maintain that of the more established ones. The public might be willing to suffer the possibility of chickenpox outbreaks, for example, in order to prevent an even minor epidemic of diphtheria or the measles.
Again, information should play a key role in the resolution of this issue. Many of the websites urging parents to carefully consider the vaccination decision do not inform parents that their decision to vaccinate may affect the overall health of the community. The CDC, for its part, does urge parents to take note of this concern. The very persons who most need to know of this concern (those seeking exemptions), however, are often those most likely to distrust CDC publications. For supposed citizen-oriented websites to urge individuals to make vaccination choices without considering how such decisions affect the community is irresponsible, especially given the scientific stability of the concept of herd immunity.
II. THE ROLE OF THE FEDERAL GOVERNMENT
Some of the problems posed to vaccination programs by exemptors and others could be partially solved through greater public awareness of the stringent safety and efficacy testing done on vaccines before they may enter the market. This section summarizes the role of FDA in the context of vaccination programs. In addition, this section will discuss other ways in which the federal government gets involved in the vaccination issue, concluding with a brief synopsis of the no-fault compensation scheme enacted pursuant to the National Childhood Vaccine Injury Act of 1986.
Though state governments determine which vaccinations are mandatory for school attendance, the federal government plays a key role in vaccination. Perhaps most importantly, the federal government regulates the safety and effectiveness of all vaccines. The FDA’s Center for Biologics Evaluation and Research (CBER) is charged with this critical task. The role of CBER ranges from pre-approval testing of potential vaccines to facility inspection to continued oversight and sampling after approval. Regulation of vaccines can be more stringent than for other biologics or drugs. Even after a vaccine is licensed, for example, FDA oversight is prevalent. Since vaccines are derived from living organisms and are particularly susceptible to contamination and other environmental factors, manufacturers usually must submit samples of each vaccine lot for testing before release.
Before a vaccine can even be licensed for distribution and use, it must go through an extensive testing process relatively similar to that of drugs and other biologics. First, a new vaccine must be tested for safety on animals. The vaccine manufacturer next must file an Investigational New Drug application (IND) with the FDA. Studies are then undertaken to ensure safety before any human testing takes place. In addition, the IND must describe the studies intended for humans.
Once these initial steps are completed, proposed vaccines must undergo three phases of clinical trials, in which the vaccine is tested on humans. Phase 1 testing looks only for very serious or very common problems. A small number of subjects (usually less than 100) are closely monitored, usually for only a few months. Testing expands in Phase 2 to begin evaluating efficacy, as well as to further test safety. Phase 2 trials can last up to two years and typically include hundreds of subjects. The final stage of testing, Phase 3, further studies safety and effectiveness. Thousands of people may be involved in this stage of testing, and if successful it can lead to application for FDA licensing.
Once the clinical trials are completed, the FDA can examine the results of the tests to determine whether the vaccine is safe and effective enough to be placed on the market. At any point in the process, the FDA may halt ongoing studies if safety concerns require such action. The FDA also reviews the data from the studies and inspects the manufacturing facility. At this point the vaccine may be licensed.
As stated above, the FDA’s role in protecting the safety and effectiveness of vaccines does not end at the licensing stage. Before any vaccines from a particular lot can be released, the manufacturer must typically submit samples for potency, safety, and purity testing. Periodic facility inspections also continue for the duration of the license. Furthermore, formal post-market studies may be conducted in order to identify problems that would not show up in pre-market clinical testing. These tests are referred to as Phase 4 tests and are not mandatory, but can help identify problems that may only occur very infrequently. Post-marketing surveillance programs are important because manufacturers are “never going to be able to do studies big enough to detect risks that might happen at a level of one in 100,000 or one in 1 million.”
The Vaccine Adverse Event Reporting System (VAERS) is another valuable tool in identifying problems with a vaccine once it has been approved for the market. VAERS was developed following Congress’s enactment of the National Childhood Vaccine Injury Act of 1986 and has become a very useful tool for identifying possible adverse effects that would otherwise escape detection. VAERS allows anyone to report a problem that may be associated with any vaccine.
It is important to keep in mind that VAERS is simply a reporting system. Experts and others use the data in VAERS to attempt to determine whether a vaccine actually causes a particular adverse effect, but the events that VAERS documents are not all caused by vaccines. It is therefore easy to understand why VAERS encourages doctors and others to report any adverse event that may be related to a vaccine. “VAERS is designed to detect signals or warnings that there might be a problem rather than to answer questions about what caused the adverse event.” It is important to keep these facts in mind when looking at VAERS data, as many of the adverse effects may be completely unrelated to the vaccine in question. Often the effects are correlated with, but unrelated to, vaccination simply because many of the problems reported are those usually associated with events happening during the vaccination period (the first few years of life).
Used correctly, VAERS can lead to useful studies and the discovery of potentially rare adverse effects. VAERS can also be used to monitor individual lots of a vaccine. Unfortunately, by encouraging individuals to report any adverse effect that may possibly have been caused by a vaccine, VAERS can provide ammunition for those claiming a definite link between a vaccine and a particular adverse effect, even if the data is silent on whether such a link exists. While VAERS is in place to help identify actual risks associated with vaccines, these risks cannot be accurately assessed solely on the basis of reported incidents of adverse effects.
The real value of VAERS lies in the testing and hypotheses that are developed in response to the data that has been reported. Because of the serious adverse effects already occurring during the typical vaccination period, it will often be easy and convenient to point to the correlation between vaccines and reported adverse events. Lost in the picture is the foundational proposition that VAERS is, at its core, a data collection system. To forego scientific inquiry and point instead to simple correlation may be convenient, but it is unwise.
The recent public discussion surrounding the use of thimerosal as a preservative in vaccines helps to illustrate the importance of the FDA and other factors in furthering the goals of vaccine safety and public confidence in the entire safety regulatory process. Thimerosal is a mercury-containing organic compound that for many years has been used as a preservative in vaccines to help prevent contamination with microbes that could potentially be fatal. Recently, fears that mercury at very low levels may be toxic to the brain have raised concern among many in the public about allowing the use of thimerosal in vaccines. Many began to fear a connection between thimerosal and autism. Standard FDA testing of lots, as well as studies measuring the amount of mercury contained in the standard immunization schedule versus accepted safe amounts, did not lead to safety concerns sufficient to pull thimerosal from the market. Though one committee (the Immunization Safety Review Committee, commissioned by the Institute of Medicine) concluded that a theoretical link between thimerosal and autism was biologically plausible, most health experts continue to assert that there simply is no scientific evidence of a link between the two.
During this time period FDA performed additional tests to verify or refute the supposed link between thimerosal and autism. In 1999, FDA performed a comprehensive study and review of thimerosal use in vaccines for children. This review revealed no risk from thimerosal use, other than “local hypersensitivity reactions.” Indeed, none of the standard safety protocols in place suggested or required that FDA pull thimerosal from the market. This is not to say, however, that no risk existed. As is clear from the foregoing summary of FDA vaccine approval, not all adverse effects will be known from clinical trials. It may take years or longer to assess some of the risks of vaccines, including the risk of thimerosal as a preservative.
Continued public concern over the safety of thimerosal caused FDA to begin to work with vaccine manufacturers in order to reduce or eliminate thimerosal from vaccines as a precautionary measure. About this time, the American Academy of Pediatrics and the Public Health Service urged the removal of thimerosal from vaccines. Today, with the exception of the inactivated influenza vaccine, all recommended childhood vaccines are either thimerosal free or contain only trace amounts of the compound. Even though the risk may not have been as great as feared by the public or even existent at all, if the new vaccines are equally effective, the elimination of thimerosal from vaccines can probably be seen as a safety improvement, albeit at the expense of the added research and development needed to create the new thimerosal-free vaccines.
Rather than quell the existing safety concerns, this action led many of those who had decried the use of thimerosal to accuse FDA of participating in a cover-up to protect vaccine manufacturers. Government agencies, for their part, continue to claim that vaccines with thimerosal are as safe as thimerosal-free vaccines, suggesting that the added development may have been superfluous. While this may be so, the availability and now prevalence of thimerosal-free vaccines does provide the scientific and medical community with a new means of assessing the possible autism-causing effects of thimerosal. Namely, since thimerosal is suspected to cause autism within the first few years of life (the routine vaccination calendar), those who were vaccinated in the years since thimerosal-free vaccines have comprised the overwhelming majority of vaccines (that is, those born after 2001) would be expected to experience lower incidences of autism than the groups vaccinated with thimerosal-containing vaccines.
In spite of the potentially costly decision to encourage the development of thimerosal-free vaccines when there is no sufficient safety concern to pull thimerosal from the market, FDA and other government officials have had little success in assuaging the fears and concerns of thimerosal critics. Scientific arguments often fail to persuade, either because they are inconclusive or because of a perceived bias favoring vaccine manufacturers. To back up their own arguments, thimerosal critics rarely point to scientific studies. Instead, their reasoning seems to stem more from anecdotal evidence and comparison of thimerosal (which contains ethyl-mercury) to methyl-mercury-containing fish. Representative Dan Burton (R-Indiana), a key supporter of the fight against thimerosal, explained that his belief in the toxicity of thimerosal stemmed from a personal episode: “[m]y grandson received nine shots in one day, seven of which contained thimerosal, which is 50 percent mercury as you know, and he became autistic a short time later.” Others point to the rise in autism rates in the past twenty years and put the onus on the medical community to prove that this rise is not due to thimerosal.
The response of health officials has been to ask why the burden should be placed on them to disprove a link between thimerosal and autism; cell phones, ultrasound, or diet soda could just as easily be the culprit. Indeed, the typical response to those charging vaccination with causing many of the adverse effects occurring in life’s first few years is to point out that usually such accusations are based on nothing more than the temporal proximity of the vaccine and the illness. Some have suggested that the rates of autism may be on the rise not because of thimerosal, but because of generally more accurate diagnosis of the affliction. In the past, an autistic child may have been wrongfully diagnosed with other mental disorders. Figures showing a correlation between the rise in autism and the drop in other diagnosed mental disorders bolster such assertions, and suggest that vaccination may simply be a convenient scapegoat.
As the thimerosal issue makes clear, vaccines often provoke strong feelings amongst various segments of the population. Proper consideration of public reaction to its actions is a delicate aspect of FDA regulation of vaccine safety. To complicate matters further, one can easily imagine an equally vehement response and similar claims of conspiracy had the FDA not worked to reduce thimerosal from vaccines as a precautionary measure. Indeed, public confidence in the safety of vaccines is often influenced by factors outside the typical FDA calculus. Though FDA must act in the interests of the general safety regardless of public opinion, it may sometimes be necessary for FDA to consider public opinion, at least when exercising discretionary oversight. After all, the entire VAERS system is to a large extent dependant on public cooperation. Nevertheless, when the choice is between FDA popularity and doing what is right for the safety of Americans, the FDA should not allow itself to be swayed by a misinformed public.
Vaccine Injury Compensation Program
Congressional reaction to safety concerns goes beyond the adverse reporting system VAERS. The National Childhood Vaccine Injury Act of 1986, which created VAERS, also created a no-fault compensation scheme for people injured or killed by vaccines as an alternative to the traditional tort system. This system was intended to efficiently and rapidly compensate those who are actually injured by vaccines while maintaining an environment in which further vaccine research and safety improvement could exist. The situation giving rise to this compensation program sounds remarkably similar to the more recent concerns surrounding thimerosal:
In the early 1980's, reports of harmful side effects following the DTP (diphtheria, tetanus, pertussis) vaccine posed major liability concerns for vaccine companies and health care providers, and caused many to question the safety of the DTP vaccine. Parents began filing many more lawsuits against vaccine companies and health care providers. Vaccination rates among children began to fall and many companies that develop and produce vaccines decided to leave the marketplace, creating significant vaccine shortages and a real threat to the Nation’s health.
Funding for the no-fault compensation scheme initially came from Congressional grants of federal tax dollars totaling $110 million per year. Since October 1, 1988, funding has proceeded from the Vaccine Injury Compensation Trust Fund, which is funded by a $0.75 excise tax on all doses of vaccines covered under the program.
One may wonder what makes vaccines worthy of an alternative dispute resolution system. Perhaps it is the result of the power of the vaccine manufacturing lobby or simply an attempt by Congress to pass some legislation in the face of strong public sentiment. Although these reasons may appear plausible, it seems more likely to me that the Act created this no-fault compensation scheme because of the mandatory nature of vaccination. For those injured by other medical devices or drugs, the traditional tort system or medical insurance seem the proper means of addressing the issue. When people are told to undertake a medical procedure they may not agree with because it helps further a public goal, however, it may make sense to have a system in place whereby they can obtain relief quickly if harmed by the procedure. Moreover, because certain vaccines may be closely associated with particular adverse effects, the efficiency of a no-fault scheme may trump the standard fact-finding processes of the legal system. The government has chosen to enact such a no-fault scheme, and err on the side of compensation.
III. ANALYTICAL MEANS OF ADDRESSING THE ISSUE
The concerns and problems raised in the context of mandatory vaccination programs do not readily suggest a simple answer. In examining the issue, I came across two particularly useful tools for analyzing the problem. The first comes from an old episode of The Andy Griffith Show in which a local farmer refused to accept a vaccination from the local nurse. In addition to providing substantial entertainment to the viewer, the characters can be viewed metaphorically to represent the various parties in the mandatory vaccination debate. The episode’s solution, in turn, sheds some light on the current debate.
This section will also utilize the analytical framework of economic analysis. Though not as enjoyable a topic as The Andy Griffith Show, economic theory helps to reshape the vaccination discussion and greatly facilitates the process of assessing the various positions.
“We got to get folks to take their shots” – Sheriff Andy Taylor
The Andy Griffith Show addressed the concept of popular resistance to universal vaccination over forty years ago. In “The County Nurse,” Sheriff Andy Taylor confronted a local nurse who was trying to bring everyone up to date on their tetanus shots. Not surprisingly, at least to Andy, many of the mountain farmers had not been inoculated. The naïve nurse would soon discover the reason for the low vaccination rate.
Rafe Hollister, one of the leading farmers in Mayberry, had little use for modern medicine or doctors in general. “We don’t need any nurse, nobody gets sick up here.” Thermometers? “I know when I got a fever, I’m hot.” Stethoscopes? “I know my heart’s beating, I’m alive ain’t I?” But his strongest objection was saved for vaccinations: “I ain’t never been jabbed and I ain’t fixin’ to be.” Such were the views that the nurse was up against in her attempt to achieve 100% vaccination rates.
Rafe Hollister’s reasons for opposing vaccination went beyond his desire to avoid getting “jabbed.” He was a farmer who lived off the land, and when he got sick he let his body fight the sickness naturally. His daddy had lived to the age of hundred and he aimed to do the same. The concept of a vaccination was certainly something foreign to him, as was the idea that a health official could force him to do anything. Even in the wake of the nurse’s impassioned plea to accept a shot that could someday save his life, he retorted simply, “I done alright before you come around and I’m doing alright now.”
Although the county nurse was not acting pursuant to a mandatory vaccination program, under the circumstances her attempts to get Rafe inoculated were pretty forceful. The nurse was accompanied by the local sheriff to Rafe’s farm to try to convince him to take the shot, and when he refused, the sheriff and nurse continued to attempt to make him acquiesce. When Deputy Barney Fife heard of Rafe’s stubbornness, he insisted the nurse return to Rafe’s farm with him to force Rafe to take the shot. After all, boasted the deputy, “Rafe Hollister’s like a child and he’s gotta be treated like one...I’ll make him take his shot.” When the deputy arrived at Rafe’s farm yelling that he was forcing Rafe to accept the vaccination, Rafe decided to fight the mandatory vaccination by drawing his rifle and forcing the deputy to leave the farm.
In a classic manifestation of the early spirit of the television series, Sheriff Andy Taylor finally convinced Rafe to take the shot through a little reverse psychology. Andy began by facetiously praising Rafe’s refusal to take the shot as stemming from Rafe’s desire for immortality. Namely, by refusing to take the shot, Rafe was sure to become the impetus for all the other townspeople not to neglect to take their shots. Unfortunately for Rafe, this heroic stature would only be achieved posthumously, as he will have succumbed to a violent and painful death from tetanus. As Andy explained to Rafe, someday, after getting cut by a rusty saw or bitten by an animal, without the shot he’ll “be a cinch to go.” Eschewing the chance to be a dead hero, Rafe finally took the shot.
Sheriff Andy Taylor
Vaccination has changed the modern world. Indeed, it has led to the elimination or significant decline of many diseases that once posed significant and potentially deadly health risks. Public health officials in the United States have managed to institute a program that, though subject to variations on a state by state basis, essentially mandates certain vaccinations as a requirement for school attendance. While these vaccination programs are touted by most public health officials, a significant number of people oppose mandatory vaccination. The County Nurse episode helps illuminate the perspectives of the various sides of the issue, as well as one possible solution.
The nurse herself represents the public health officials. Though she is not implementing a mandatory vaccination program, her stated goal is to inoculate 100% of the population. As mentioned above, she has the assistance of local law enforcement and she is quite persistent. Rafe Hollister, the stubborn farmer, represents those within the community who oppose or resist mandatory vaccination programs. His reasons initially rest on a general reluctance to stray from natural medicine. In this way he represents the contingent of society that scientists and medical researchers will always find difficult to convince of any developments in the medical field. In many ways, he is comparable to the plaintiff in Jacobson . Andy and Barney can be seen as the arms of the state that are entrusted with carrying out the general vaccination plan. Their varying styles can be seen as varying state requirements and enforcement options for vaccination.
Though these comparisons may seem elementary and of little value, the character development that the characters undertake during the episode greatly increases the episode’s usefulness as a surrogate for real world concerns and issues. Rafe resists the shot initially not only because he distrusts medicine in general, but also because he resents the idea that a county nurse can make him do anything. Many who resist mandatory vaccination schemes do so because of personal liberty concerns; they do not want the government to tell them what to do, especially in the context of personal medical decisions. Just as Rafe’s stance becomes more vehement the harder the nurse attempts to convince him, many who oppose mandatory vaccination see the persistence of the medical community as evidence of blind adherence to a potentially dangerous system, or worse yet as an active promotion of the special interests of the vaccine manufacturers. The episode does not paint the nurse in this way at all, however. Rather, after seeing how strongly Rafe opposes vaccination, the nurse passionately pleads with him to reconsider. Her stance truly seems to stem from a genuine concern that he not suffer the potentially terrible effects of the disease. As before, he refuses; this seems to illustrate that the stance of some may be so strong that they will never accept vaccination on the basis of arguments advanced by government officials.
Barney Fife’s insistence that Rafe accept the shot demonstrates the lack of understanding among many in the government and in the general population as to the vehemence with which those opposing mandatory vaccination hold to their views. His paternalistic stand only serves to exacerbate the situation with Rafe. Indeed, Barney Fife helps to illustrate that there cannot be a one-way solution to the issue of mandatory vaccination.
Andy Taylor’s method of convincing, which eventually carried the day, may not be very conducive to real-world implementation. After all, it is unrealistic to think that reverse psychology will convince those currently opposed to vaccination programs to change their minds. What I think is important to notice, however, is the role information can play in this issue. Andy finally convinces Rafe Hollister to take his shot after describing the horrible effects of the disease and how likely Rafe is to contract it. Similarly, any solution to the issue of mandatory vaccination holdouts must rely on increased information dissemination. That the information in the episode came from a trustworthy source may also have been crucial, which seems to imply that public health officials may need to work more closely with local personnel in order to obtain higher vaccination rates.
Because this episode deals with the vaccine for tetanus, a non-communicable disease, the usual community-based arguments in favor of vaccination do not enter the equation. Extra-personal consequences of Rafe’s decision to vaccinate do exist, however. Most importantly, as the unofficial leader of the farming community, his decision will be followed by the other farmers. This is shown both in Andy’s assurances to the nurse that Rafe is the most important of the farmers to convince on the issue and later, after Rafe has decided to get the shot, in his promise to the nurse that all she has to do is come with him and he’ll get all the farmers to take their shots. Perhaps those parents who support vaccination can help bring about higher vaccination rates by being more vocal and persistent with their neighbors who oppose vaccination programs.
Economic analysis provides a useful theoretical basis for evaluating the competing sides of the vaccination debate. Arguments regarding the wisdom of the current vaccination policy can often be recast as economic questions involving a cost-benefit analysis.
When an epidemic breaks out, for example, the benefits of vaccination (protection from the disease both for the individual and for society through herd immunity) seem more clearly to outweigh the costs (potential side effects of the vaccine, decreased ability of the immune system to defend the body from variant strands of the disease, or personal or religious objection). Vaccination rates would, therefore, be expected to be highest during such epidemics. Consequently, those few who continue to oppose vaccination during such epidemics would be expected to do so for only the strongest reasons. This is due to the fact that in economic terms, the opponent of vaccination would have to believe that the benefits of vaccination still do not outweigh the costs, even during an epidemic. This might stem from a relative undervaluation of the benefits of vaccination (perhaps due to a belief that contracting the disease would not be so bad) or a relative overvaluation of the costs of vaccination (possibly due to the greater cost to the conscience of the personal or religious opponent of vaccination) or some combination of both. Medical exemptions directly illustrate this cost-benefit analysis: for a person likely to suffer serious side effects from a vaccine, the cost of vaccination is much greater than the cost to the average individual. Even in a time of epidemic, therefore, vaccination might not be rational for such an individual.
This economic analysis of vaccination is well illustrated by the facts of Jacobson v. Massachusetts , the first Supreme Court case addressing the constitutionality of mandatory vaccination legislation. The case involved a Massachusetts statute allowing local authorities to mandate vaccination for smallpox if necessary for the public health and safety. Subsequently, and upon a determination that smallpox was “prevalent to some extent” and “continues to increase,” the city of Cambridge passed a mandatory vaccination ordinance. This ordinance represented the economic determination that the benefit of mandatory vaccination outweighed the cost of supplying vaccines, finding and prosecuting holdouts (such as Jacobson), and the decreased liberty of individuals to be permitted to decide whether to vaccinate.
Jacobson subsequently challenged his prosecution under the ordinance by claiming it to be an unconstitutional denial of his liberty under the 14th Amendment (as well as in violation of the Preamble and the “spirit” of the Constitution, arguments that were summarily dismissed).
Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. Three specific hypotheses have been proposed: (1) the combination measles-mumps-rubella vaccine causes autism by damaging the intestinal lining, which allows the entrance of encephalopathic proteins; (2) thimerosal, an ethylmercury-containing preservative in some vaccines, is toxic to the central nervous system; and (3) the simultaneous administration of multiple vaccines overwhelms or weakens the immune system. We will discuss the genesis of each of these theories and review the relevant epidemiological evidence.
A worldwide increase in the rate of autism diagnoses—likely driven by broadened diagnostic criteria and increased awareness—has fueled concerns that an environmental exposure like vaccines might cause autism. Theories for this putative association have centered on the measles-mumps-rubella (MMR) vaccine, thimerosal, and the large number of vaccines currently administered. However, both epidemiological and biological studies fail to support these claims.
On 28 February 1998, Andrew Wakefield, a British gastroenterologist, and colleagues  published a paper in The Lancet that described 8 children whose first symptoms of autism appeared within 1 month after receiving an MMR vaccine. All 8 of these children had gastrointestinal symptoms and signs and lymphoid nodular hyperplasia revealed on endoscopy. From these observations, Wakefield postulated that MMR vaccine caused intestinal inflammation that led to translocation of usually nonpermeable peptides to the bloodstream and, subsequently, to the brain, where they affected development.
Several issues undermine the interpretation by Wakefield et al.  of this case series. First, the self-referred cohort did not include control subjects, which precluded the authors from determining whether the occurrence of autism following receipt of MMR vaccine was causal or coincidental. Because ∼50,000 British children per month received MMR vaccine between ages 1 and 2 years—at a time when autism typically presents—coincidental associations were inevitable. Indeed, given the prevalence of autism in England in 1998 of 1 in 2000 children , ∼25 children per month would receive a diagnosis of the disorder soon after receiving MMR vaccine by chance alone. Second, endoscopic or neuropsychological assessments were not blind, and data were not collected systematically or completely. Third, gastrointestinal symptoms did not predate autism in several children, which is inconsistent with the notion that intestinal inflammation facilitated bloodstream invasion of encephalopathic peptides. Fourth, measles, mumps, or rubella vaccine viruses have not been found to cause chronic intestinal inflammation or loss of intestinal barrier function. Indeed, a recent study by Hornig et al.  found that the measles vaccine virus genome was not detected more commonly in children with or without autism. Fifth, putative encephalopathic peptides traveling from the intestine to the brain have never been identified. In contrast, the genes that have been associated with autism spectrum disorder to date have been found to code for endogenous proteins that influence neuronal synapse function, neuronal cell adhesion, neuronal activity regulation, or endosomal trafficking .
Although no data supporting an association between MMR vaccine and autism existed and a plausible biological mechanism was lacking, several epidemiologic studies were performed to address parental fears created by the publication by Wakefield et al.  (table 1). Fortunately, several features of large-scale vaccination programs allowed for excellent descriptive and observational studies—specifically, large numbers of subjects, which generated substantial statistical power; high-quality vaccination records, which provided reliable historical data; multinational use of similar vaccine constituents and schedules; electronic medical records, which facilitated accurate analysis of outcome data; and the relatively recent introduction of MMR vaccine in some countries, which allowed for before and after comparisons.
Studies that fail to support an association between measles-mumps-rubella vaccine and autism.
Studies that fail to support an association between measles-mumps-rubella vaccine and autism.
Ecological studies.Researchers in several countries performed ecological studies that addressed the question of whether MMR vaccine causes autism. Such analyses employ large databases that compare vaccination rates with autism diagnoses at the population level.
In the United Kingdom, researchers evaluated 498 autistic children born from 1979 through 1992 who were identified by computerized health records from 8 health districts . Although a trend toward increasing autism diagnoses by year of birth was confirmed, no change in the rates of autism diagnoses after the 1987 introduction of MMR vaccine was observed. Further, MMR vaccination rates of autistic children were similar to those of the entire study population. Also, investigators did not observe a clustering of autism diagnoses relative to the time that children received MMR vaccine, nor did they observe a difference in age at autism diagnosis between those vaccinated and not vaccinated or between those vaccinated before or after 18 months of age. These authors also found no differences in autism rates among vaccinated and unvaccinated children when they extended their analysis to include a longer time after MMR exposure or a second dose of MMR .
Also in the United Kingdom, researchers performed a time-trend analysis using the General Practice Research Database—a high-quality, extensively validated electronic medical record with virtually complete vaccination data . More than 3 million person-years of observation during 1988–1999 confirmed an increase in autism diagnoses despite stable MMR vaccination rates.
In California, researchers compared year-specific MMR vaccination rates of kindergarten students with the yearly autism case load of the California Department of Developmental Services during 1980–1994 . As was observed in the United Kingdom, the increase in the number of autism diagnoses did not correlate with MMR vaccination rates.
In Canada, researchers estimated the prevalence of pervasive developmental disorder with respect to MMR vaccination in 27,749 children from 55 schools in Quebec . Autism rates increased coincident with a decrease in MMR vaccination rates. The results were unchanged when both exposure and outcome definitions varied, including a strict diagnosis of autism.
Additional population-based studies considered the relationship between MMR vaccine and the “new variant” form of autism proposed by Wakefield et al. —specifically, developmental regression with gastrointestinal symptoms. Although it is difficult to analyze such a phenomenon when it is unclear that one exists (which complicates the formulation of a case definition), conclusions may be gleaned from the data with respect to developmental regression alone (i.e., autism irrespective of coincident bowel problems).
In England, researchers performed a cross-sectional study of 262 autistic children and demonstrated no difference in age of first parental concerns or rate of developmental regression by exposure to MMR vaccine . No association between developmental regression and gastrointestinal symptoms was observed.
In London, an analysis of 473 autistic children used the 1987 introduction of MMR to compare vaccinated and unvaccinated cohorts . The incidence of developmental regression did not differ between cohorts, and the authors observed no difference in the prevalence of gastrointestinal symptoms between vaccinated and unvaccinated autistic children.
Two conclusions are evident from these data. First, the explicit consideration of developmental regression among autistic children does not alter the consistent independence of MMR vaccine and autism. Second, these data argue against the existence of a new variant form of autism.
Retrospective, observational studies.Four retrospective, observational studies addressed the relationship between MMR vaccine and autism.
In the United Kingdom, 71 MMR-vaccinated autistic children were compared with 284 MMR-vaccinated matched control children through use of the Doctor's Independent Network, a general practice database . The authors observed no differences between case and control children in practitioner consultation rates—a surrogate for parental concerns about their child's development—within 6 months after MMR vaccination, which suggests that the diagnosis of autism was not temporally related to MMR vaccination.
In Finland, using national registers, researchers linked hospitalization records to vaccination records in 535,544 children vaccinated during 1982–1986 . Of 309 children hospitalized for autistic disorders, no clustering occurred relative to the time of MMR vaccination.
In Denmark, again using a national registry, researchers determined vaccination status and autism diagnosis in 537,303 children born during 1991–1998 . The authors observed no differences in the relative risk of autism between those who did and those who did not receive MMR vaccine. Among autistic children, no relationship between date of vaccination and development of autism was observed.
In metropolitan Atlanta, using a developmental surveillance program, researchers compared 624 autistic children with 1824 matched control children . Vaccination records were obtained from state immunization forms. The authors observed no differences in age at vaccination between autistic and nonautistic children, which suggests that early age of MMR vaccine exposure was not a risk factor for autism.
Prospective observational studies.Capitalizing on a long-term vaccination project maintained by the National Board of Health, investigators in Finland performed 2 prospective cohort studies. Researchers prospectively recorded adverse events associated with MMR-vaccinated children during 1982–1996 and identified 31 with gastrointestinal symptoms; none of the children developed autism . A further analysis of this cohort revealed no vaccine-associated cases of autism among 1.8 million children . Although this cohort was analyzed using a passive surveillance system, the complete absence of an association between gastrointestinal disease and autism after MMR vaccination was compelling.
Thimerosal—50% ethylmercury by weight—is an antibacterial compound that has been used effectively in multidose vaccine preparations for >50 years  (thimerosal is not contained in live-virus vaccines, such as MMR). In 1997, the US Food and Drug Administration Modernization Act mandated identification and quantification of mercury in all food and drugs; 2 years later, the US Food and Drug Administration found that children might be receiving as much as 187.5 µg of mercury within the first 6 months of life. Despite the absence of data suggesting harm from quantities of ethylmercury contained in vaccines, in 1999, the American Academy of Pediatrics and the Public Health Service recommended the immediate removal of mercury from all vaccines given to young infants . Widespread and predictable misinterpretation of this conservative, precautionary directive, coupled with a public already concerned by a proposed but unsubstantiated link between vaccination and autism, understandably provoked concern among parents, which led to the birth of several antimercury advocacy groups. However, because the signs and symptoms of autism are clearly distinct from those of mercury poisoning, concerns about mercury as a cause of autism were—similar to those with MMR vaccine—biologically implausible ; children with mercury poisoning show characteristic motor, speech, sensory, psychiatric, visual, and head circumference changes that are either fundamentally different from those of or absent in children with autism. Consistent with this, a study performed by scientists at the Centers for Disease Control and Prevention years later showed that mercury in vaccines did not cause even subtle signs or symptoms of mercury poisoning .
Despite the biological implausibility of the contention that thimerosal in vaccines caused autism, 7 studies—again descriptive or observational—were performed (table 2). Four other studies have been reviewed in detail elsewhere  but are not discussed here because their methodology is incomplete and unclear and, thus, cause difficulty in drawing meaningful conclusions.
Ecological studies.Three ecological studies performed in 3 different countries compared the incidence of autism with thimerosal exposure from vaccines. In each case, the nationwide removal of thimerosal—which occurred in 1992 in Europe and in 2001 in the United States—allowed robust comparisons of vaccination with thimerosal-containing and thimerosal-free products, as follows:
In Sweden and Denmark, researchers found a relatively stable incidence of autism when thimerosal-containing vaccines were in use (1980–1990), including years when children were exposed to as much as 200 µg of ethylmercury (concentrations similar to peak US exposures) . However, in 1990, a steady increase in the incidence of autism began in both countries and continued through the end of the study period in 2000, despite the removal of thimerosal from vaccines in 1992.
In Denmark, researchers performed a study comparing the incidence of autism in children who had received 200 µg (1961–1970), 125 µg (1970–1992), or 0 µg of thimerosal (1992–2000) and again demonstrated no relationship between thimerosal exposure and autism .
In Quebec, researchers grouped 27,749 children from 55 schools by date of birth and estimated thimerosal exposure on the basis of the corresponding Ministry of Health vaccine schedules. School records were obtained to determine age-specific rates of pervasive developmental disorder . Thimerosal exposure and pervasive developmental disorder diagnosis were found to be independent variables. Similar to previous analyses, the highest rates of pervasive developmental disorder were found in cohorts exposed to thimerosal-free vaccines. The results were unchanged when both exposure and outcome definitions varied.
Cohort studies.Four cohort studies that examined thimerosal exposure and autism have been performed, as follows:
In Denmark, researchers examined >1200 children with autism that was identified during 1990–1996, which comprised ∼3 million person-years. They found that the risk of autism did not differ between children vaccinated with thimerosal-containing vaccines and those vaccinated with thimerosal-free vaccines or between children who received greater or lower quantities of thimerosal . They also found that the rates of autism increased after the removal of thimerosal from all vaccines.
In the United States, using the Vaccine Safety Data Link, researchers at the Centers for Disease Control and Prevention examined 140,887 US children born during 1991–1999, including >200 children with autism . The researchers found no relationship between receipt of thimerosal-containing vaccines and autism.
In England, researchers prospectively followed 12,810 children for whom they had complete vaccination records who were born during 1991–1992, and they found no relationship between early thimerosal exposure and deleterious neurological or psychological outcomes .
In the United Kingdom, researchers evaluated the vaccination records of 100,572 children born during 1988–1997, using the General Practice Research Database, 104 of whom were affected with autism . No relationship between thimerosal exposure and autism diagnosis was observed.
Too Many Vaccines
When studies of MMR vaccine and thimerosal-containing vaccines failed to show an association with autism, alternative theories emerged. The most prominent theory suggests that the simultaneous administration of multiple vaccines overwhelms or weakens the immune system and creates an interaction with the nervous system that triggers autism in a susceptible host. This theory was recently popularized in the wake of a concession by the Vaccine Injury Compensation Program with regard to the case of a 9-year-old girl with a mitochondrial enzyme deficiency whose encephalopathy, which included features of autism spectrum disorder, was judged to have worsened following the receipt of multiple vaccines at age 19 months . Despite reassurances by the Centers for Disease Control and Prevention that the Vaccine Injury Compensation Program's action should not be interpreted as scientific evidence that vaccines cause autism, many in the lay press and the public have not been reassured.
The notion that children might be receiving too many vaccines too soon and that these vaccines either overwhelm an immature immune system or generate a pathologic, autism-inducing autoimmune response is flawed for several reasons:
Vaccines do not overwhelm the immune system. Although the infant immune system is relatively naive, it is immediately capable of generating a vast array of protective responses; even conservative estimates predict the capacity to respond to thousands of vaccines simultaneously . Consistent with this theoretical exercise, combinations of vaccines induce immune responses comparable to those given individually . Also, although the number of recommended childhood vaccines has increased during the past 30 years, with advances in protein chemistry and recombinant DNA technology, the immunologic load has actually decreased. The 14 vaccines given today contain <200 bacterial and viral proteins or polysaccharides, compared with >3000 of these immunological components in the 7 vaccines administered in 1980 . Further, vaccines represent a minute fraction of what a child's immune system routinely navigates; the average child is infected with 4–6 viruses per year . The immune response elicited from the vast antigen exposure of unattenuated viral replication supersedes that of even multiple, simultaneous vaccines.
multiple vaccinations do not weaken the immune system. Vaccinated and unvaccinated children do not differ in their susceptibility to infections not prevented by vaccines [33,–,35]. In other words, vaccination does not suppress the immune system in a clinically relevant manner. However, infections with some vaccine-preventable diseases predispose children to severe, invasive infections with other pathogens [36, 37]. Therefore, the available data suggest that vaccines do not weaken the immune system.
Autism is not an immune-mediated disease. Unlike autoimmune diseases such as multiple sclerosis, there is no evidence of immune activation or inflammatory lesions in the CNS of people with autism . In fact, current data suggest that genetic variation in neuronal circuitry that affects synaptic development might in part account for autistic behavior . Thus, speculation that an exaggerated or inappropriate immune response to vaccina-tion precipitates autism is at variance with current scientific data that address the pathogenesis of autism.
No studies have compared the incidence of autism in vaccinated, unvaccinated, or alternatively vaccinated children (i.e., schedules that spread out vaccines, avoid combination vaccines, or include only select vaccines). These studies would be difficult to perform because of the likely differences among these 3 groups in health care seeking behavior and the ethics of experimentally studying children who have not received vaccines.
Twenty epidemiologic studies have shown that neither thimerosal nor MMR vaccine causes autism. These studies have been performed in several countries by many different investigators who have employed a multitude of epidemiologic and statistical methods. The large size of the studied populations has afforded a level of statistical power sufficient to detect even rare associations. These studies, in concert with the biological implausibility that vaccines overwhelm a child's immune system, have effectively dismissed the notion that vaccines cause autism. Further studies on the cause or causes of autism should focus on more-promising leads.
Potential conflicts of interest.P.A.O. is a coinventor and patent coholder of the rotavirus vaccine Rotateq and has served on a scientific advisory board to Merck. J.S.G.: no conflicts.
Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children,
Lack of association between measles virus vaccine and autism with enteropathy: a case-control study,