Thursday, July 01, 2004

Scientists, Families, and Courts Clash Over the Elusive Causes of Autism

By: Mark Parascandola Ph.D.

Discovery that a child is autistic changes forever a parent’s hopes and dreams. Thus, when a British medical journal reported that childhood vaccinations might be a cause of autism, a storm of anxiety ensued—and the tort lawyers came on the run. Subsequent studies failed to confirm the autism-vaccine link, and the journal that published the original study retracted it. As of now, however, the lawsuits are going forward and childhood vaccination rates are dropping.

What causes autism is still unknown. When childhood vaccines were proposed as a possible cause, cautious public health leaders urged changes in vaccine formulations; tort lawyers seized a potentially lucrative opportunity. As new evidence became available, however, the proposed vaccines-autism link was largely discounted by scientists and leading science organizations. So far, that has not prevented an alarming increase in parental skepticism about childhood vaccinations, a mindset that poses a threat to public health. Has science failed us as a guide to decision making? An expert in evaluating scientific evidence argues that the real fault is an unwillingness to recognize that science must consistently revise its conclusions in the face of new evidence— not partially, or just when the revision suits us.

Autism is among the most mysterious medical conditions known to science. It occurs in people of all racial and ethnic groups and at every socioeconomic level. Defined as a complex brain disorder that inhibits a person’s ability to communicate, respond to surroundings, or form relationships, autism typically is diagnosed early, by age two or three. It is characterized by symptoms, including extreme social withdrawal, loss (or lack of development) of language, and cognitive deficits. The autistic child often engages in endlessly repetitive movements, such as circling, spinning, or rocking. For parents, the child’s world is heartbreakingly remote from any normal life.

The term “autism” is usually traced to Swiss psychiatrist Eugen Bleuler, who used it in 1911 to describe people who shut out the world and withdraw from social life. By implication, their sole focus is themselves. Thus, “autism” is derived from the Greek “autos” or self. In fact, however, Blueler and his contemporaries used the term to describe behaviors attributable to mental retardation or some other cause. Autism was not characterized as a disease until 1943, when Baltimore child psychiatrist Leo Kanner, M.D., applied the term to a specific psychological condition with a consistent pattern of symptoms observed in 11 child patients. He wrote that “there is from the start an extreme autistic aloneness that, whenever possible, disregards, ignores, shuts out anything that comes to the child from the outside.”1 

We know little about what causes autism. For decades, psychiatrists blamed parents, especially mothers. Freudian theory popular in the 1940s and 1950s proposed that autism was a psychological disturbance caused by detached, uncaring mothers. Kanner identified a “maternal lack of genuine warmth” in his autism cases, stating that autistic children were “kept neatly in refrigerators which did not defrost. Their withdrawal seems to be an act of turning away from such a situation to seek comfort in solitude.” In the 1950s, this explanation of autism was popularized by American developmental psychologist Bruno Bettelheim, Ph.D., most notably in his essay, “Joey, the Mechanical Boy.” 

Not until the 1970s did medical researchers begin to marshal evidence for other possible causes. In London, research psychiatrists Susan Folstein, M.D., and Michael Rutter, Ph.D., did a classic study of twins to determine whether autism had a genetic component. They found that it did. Autism was more likely to occur among children who shared identical genetic information, indicating that the cause of the disorder could not be solely the behavior of parents and the home environment. Subsequently, studies of people with autism found physical abnormalities in several regions of the brain, including the cerebellum, amygdala, hippocampus, septum, and mamillary bodies. Neurons in these regions appear to be smaller than normal and to have stunted nerve fibers, which can interfere with nerve signaling. These abnormalities, and the twins study, suggest that autism results from disruption of normal brain development early in the life of the fetus. 

Since the mid-1980s, advances in technology for genetic research have enabled investigators to connect specific genes, or at least regions on the human genome, with particular functions or defects. Because autism is a complex disease, unlikely to be solely caused by a single gene defect, many regions (including regions of chromosome 15 and chromosome 7) probably contribute to its development. Despite these discoveries, scientists remain puzzled about how these genetic differences lead to autism—and genetic abnormalities are now thought likely to be only part of the story. 

A striking anomaly that appears to go against the genetic hypothesis is that autism appears to be on the increase. For most of its 60-year history, autism has been considered a rare disorder, with approximately 4 cases per 10,000 children. Studies from the past 10 years, however, suggest that this was a considerable underestimate. Current figures vary from the original 4 to almost 60 per 10,000 children, depending on the place, time, country, and population from which the estimate is derived. 

The U.S. Department of Education reported that during the 1990s the number of 6 to 21- year-olds classified as having autism under the Individuals with Disabilities Education Act increased more than four times, from 1 case in 10,000 births to more then 4 per 10,000.2 The California Department of Developmental Services reported that 3,577 children with new cases of autism accessed services in 2002, compared with only 633 children in 1994. Autism is now the top disability requiring initiation of services in the state.3 If autism were solely a genetic disease, its prevalence in the population would not be expected to change substantially over a period of even decades. Does the apparent increase mean that some change in the environment is involved? 

An obvious question scientists were quick to pose is whether the apparent increase is real. Clearly, more children today than in the past are being identified as having autism. But it is possible more cases are being identified because of increased public awareness of the disease and how to diagnose it. Physicians are more aware of autism and more likely to diagnose it correctly than in the past, and parents are more aware of the disease and more likely to seek help. Also, the definition of the disease has changed; a wider range of people are now being classified as having some variant, including people with good language and thinking skills in some areas but who have unusual ways of interacting or behaving. Too, diagnosis of the disease remains somewhat subjective, based on a physician’s interpretation of clinical observations of behavior and detailed histories from families of the children. This leaves plenty of latitude for researchers and clinicians to make varying interpretations of their diagnostic assessments, and it greatly widens the capacity to accept children with social, cognitive, and behavioral problems, along with what might be called “eccentricity” in former times, as being diseased. Therefore, although the “refrigerator mother” theories of the mid20th century are now debunked, the true causes of autism remain elusive.

A PRIME SUSPECT IS IDENTIFIED

A promising lead came in 1998. A team of researchers at the Royal Free Hospital in London, led by British gastroenterologist Andrew Wakefield, M.D., claimed the discovery of a new syndrome in a group of 12 children who shared a history of chronic intestinal disease and a sudden loss of behavioral skills. In most of the cases, autism was diagnosed for these behavioral problems. Also in most cases, the onset of behavioral problems occurred shortly after the child had received the standard measles, mumps, rubella (MMR) vaccine. 

Wakefield’s findings were published in the British medical journal the Lancet in February 1998 and widely reported in British news media. The authors of the article inserted the usual scientific caveats about the limitations of their methods and acknowledged that “[w]e did not prove an association between measles, mumps and rubella vaccine and the syndrome described.”4 This did not seem to matter; the suggestion of a scientifically established link was more than sufficient to raise alarms. Then, a larger study in which Wakefield was involved produced evidence to suggest that children with the new syndrome had measles viruses in their guts more often than healthy children. The researchers hypothesized that exposure to the measles virus in the MMR vaccine (live but “attenuated”) was the mechanism by which the vaccine could cause autism. 

Overall, this evidence linking the vaccine and autism was extremely limited, and other studies at the time showed no association. The National Board of Health of Finland had routinely collected information about adverse events in children receiving the vaccine since 1982, but by 1996, only 31 instances of gastrointestinal symptoms had been reported among more than three million vaccine recipients. There was no evidence of the epidemic proportions of gastrointestinal disorders and behavioral changes that Wakefield’s findings would predict. 

Scientists recognized early on some of the limitations to Wakefield’s study, such as the small number of patients in the study and the potential for bias. In particular, researchers were concerned that Wakefield’s study relied on parents’ own assessments of when behavioral changes became evident in their children. Epidemiologists are well aware of a phenomenon called “recall bias,” in which parents can be more likely to attribute specific behaviors or symptoms to the vaccination because they seek an explanation for their children’s disease. 

Officials worried that parents would not allow their children to receive the vaccine because of the Wakefield report, and, if such resistance spread, lack of immunity could trigger a disease outbreak. 

Despite the lack of proof, the claims about the MMR vaccine suggested to the public health community that they faced an impending crisis. Officials worried that parents would not allow their children to receive the vaccine because of the Wakefield report, and, if such resistance spread, lack of immunity could trigger a disease outbreak. The United Kingdom Medical Research Council quickly reassured parents that the MMR vaccine was safe in spite of the Wakefield report. An ad hoc group of some 30 experts in virology, gastroenterology, psychiatry, and epidemiology was hastily assembled to review the findings and concluded that no evidence would warrant a change in vaccination policy. Vaccine scientists from the U.S. Centers for Disease Control and Prevention (CDC) warned that vaccine hazard scares “may snowball into societal tragedies when the media and the public confuse association with causality and shun immunization.”5 

IN THE UNITED STATES, A SUBPLOT UNFOLDS

Meanwhile, in the United States, a subplot of the story was unfolding. In 1997, the U.S. Congress ordered the U.S. Food and Drug Administration (FDA), via the FDA Modernization Act, to assess health risks from the presence of mercury in all foods and drugs. This mandate led the FDA to investigate a preservative called thimerosal, which vaccine makers had been adding to their products since the 1930s to kill potentially dangerous bacteria. Thimerosal consists of approximately 50 percent mercury (by weight), and mercury at high doses is known to damage brain cells. Although the doses of mercury found in vaccines were extremely low, the FDA investigation revealed that some infants, depending on the vaccine formulation, the number of vaccinations, and the individual infant’s weight, could be exposed to a cumulative level of mercury that exceeded safety guidelines. 

No definitive evidence was available that these low doses could cause harm, but medical authorities urged a precautionary approach. In September 1999, the U.S. Public Health Service and the American Academy of Pediatrics issued a joint statement, acknowledging the dilemma posed by the “weighing of two different types of risks,” the risk of vaccine-preventable infectious diseases and the risk (albeit unknown and likely small) of exposure to thimerosal. The statement called on drug manufacturers “to eliminate or reduce as expeditiously as possible the mercury content of their vaccines.” Since then, U.S. manufacturers removed thimerosal or reduced it to trace amounts in all childhood vaccines, with the exception of inactivated influenza vaccine (a preservative-free version of this vaccine is available, but the supply is currently limited). Thimerosal has also been removed or reduced in many adult vaccines, though it is still present in formulations such as the influenza and tetanus vaccines.6 

In 2001, the U.S. Institute of Medicine of the National Academy of Sciences created an Immunization Safety Review Committee to address the various vaccine safety issues in the news at the time. (The committee receives financial support from the U.S. Public Health Service, but it is mandated to provide independent advice to policymakers, because the Institute of Medicine is part of the nongovernmental, nonprofit National Academies.) The Immunization Safety Review Committee comprises 14 members with expertise in pediatrics, neurology, genetics, epidemiology, immunology, and risk perception. The committee’s first meeting addressed the evidence that linked the MMR vaccine with autism. After reviewing available studies and taking testimony of experts, the committee concluded that “current scientific evidence neither proves nor disproves a link between the mercury-containing preservative thimerosal and neurodevelopmental disorders in children.” The committee did acknowledge, however, that if thimerosal got into the brain, it was “biologically plausible” that it could cause brain damage. The committee said prudence dictated that precautionary measures be taken to prevent exposing infants, children, and pregnant women to thimerosal and that thimerosal-free vaccines should be used for those groups. 

AN OUTBREAK OF LITIGATION

Joseph and Theresa Counter’s son, Joseph Alexander, born in 1996, appeared to be normal and healthy until he was two years old. Then he abandoned the limited vocabulary he had developed and would only communicate by screaming. Autism was diagnosed and blood tests revealed high levels of mercury exposure. The Counters began researching Web sites and contacting support groups for parents of autism. By this time, Wakefield’s study had received substantial media attention, and public concern was growing about a possible link between childhood vaccines and autism. In May 2001, the Counters sued the principal vaccine manufacturers (American Home Products Corp, Aventis Pasteur Inc., Merck & Co., and GlaxoSmithKline), the makers of thimerosal (Uriach Corp. and Emerck Inc.), and Eli Lilly & Co., which had invented the product and promoted its use as a preservative.

Since then, dozens of lawsuits, including several class actions, have been introduced around the country, claiming compensation for allegedly vaccine-induced neurologic disorders. A coalition of about 30 law firms is gathering evidence and preparing to bring these cases to trial. The defendant companies claim there is no evidence to implicate their products as causes of autism. Some autistic children show high levels of mercury, but the defendants maintain that the mercury exposure could be from other sources of mercury to which children can be exposed. 

Some autistic children show high levels of mercury, but the defendants maintain that the mercury exposure could be from other sources of mercury to which children can be exposed.

The biggest challenge of these cases is proving that the vaccine caused a given child’s condition. Over the past decade, U.S. courts imposed more stringent rules about scientific testimony in the courtroom, seeking to screen out testimony that is merely speculative. This trend began with a landmark 1993 U.S. Supreme Court ruling, Daubert v. Merrell Dow Pharmaceuticals. In that case, parents claimed that the use of the morning sickness drug Benedectin caused birth defects in their children, but their evidence was limited to a few animal studies and unpublished reanalyses of data from negative epidemiologic studies. The Supreme Court agreed to hear the case because the legal system had been grappling with the appropriate standards for admitting scientific testimony into the courtroom, particularly for “toxic tort” lawsuits. The Daubert decision made judges responsible for ensuring that a scientific expert’s testimony was based on evidence that was both reliable and relevant. 

But vaccines introduce still another twist in the legal arena. Because they have enormous public health value, vaccines are treated differently than other products, even other pharmaceutical products. Parents who bring a vaccine injury lawsuit are required to take their case to the National Vaccine Injury Compensation Program before going to a civil court. That program was established by the National Childhood Vaccine Injury Act of 1986, which was intended to protect vaccine manufacturers from overwhelming liability that could lead them to simply stop making vaccines entirely. The reasoning was that, because continued availability of vaccines was so vital to the nation’s health, the law would protect the market while ensuring that deserving victims were compensated according to fair, predictable rules. 

Advocates for families claiming vaccine injuries countered that these special rules deprive parents of autistic children of their right to make their case in court. One obstacle facing parents is that the Vaccine Act sets a “statute of limitations” of 36 months from when disease symptoms are first discovered for parents to bring their case. But public attention about a possible link between childhood vaccines and autism is relatively new. Thus, parents whose children began showing signs of autism more than three years ago would be automatically barred from receiving compensation, even if they were not aware until now that the disease might be vaccine related. Indeed, even if future studies were to demonstrate unequivocally that thimerosal-containing vaccines do cause autism, such parents would not be able to bring a case. Moreover, when some claimants attempted to bring their cases before ordinary civil courts, the courts sent them back to the Compensation Program. 

Advocates of families with autistic children, along with other groups concerned about vaccine injuries, have pushed for reform of the Compensation Program to remove some of its restrictions. For example, Congressman Dan Burton (R-IN), whose grandson experienced symptoms of autism shortly after receiving a routine round of immunizations, championed efforts to revamp the program. Burton publicly stated that he believes that thimerosal-containing vaccines are responsible for a substantial proportion of the increase in autism in the United States. 

TRIAL IN THE COURT OF PUBLIC OPINION

Over the past year, the dynamics of the debate over a possible link between vaccines and autism changed dramatically. Students of the history of science like to remind us that “science does not occur in a vacuum,” and the case of vaccines and autism gives us an outstanding example of that maxim. The courts and members of Congress weighed in on issues of scientific methodology. Prominent scientists and public health leaders were charged with being influenced by conflicts of interest. Much of the public, it seems, has lost trust in government health officials as a source of objective, authoritative advice on the risks and benefits of childhood vaccinations. 

In 2003, a large study by the CDC, published in the journal Pediatrics, failed to find any association between exposure to vaccines containing thimerosal and neurodevelopmental disorders, including autism. Researchers from CDC and participating health providers analyzed the computerized vaccination and medical records of more than 140,000 children aged from birth to 9 years. The study looked at a wide range of neurodevelopmental problems, including autism, attention deficit disorder, language delays, sleep disorders, emotional disorders, and tics. None of them were shown to be consistently associated with thimerosal-containing vaccines. In some groups studied, children receiving vaccines containing thimerosal were more likely to develop speech and language disorders, which could potentially be related to autism. But because this was not observed in all the participating health provider organizations, the researchers could not rule out the possibility that this association was due to some type of bias or statistical anomaly. Frank DeStefano, M.D., M.P.H., one of the CDC study authors, was quoted in newspapers summarizing the findings: “The final results of the study show no statistical association between thimerosal vaccines and harmful health outcomes in children, in particular autism and attention deficit disorder.” 

This conclusion was strongly criticized by the families of autistic children. Groups such as the National Autism Association and Moms On A Mission For Autism challenged the conclusions and accused CDC researchers of minimizing the effects of thimerosal. Congressman Dave Weldon, M.D. (R-FL), a physician who has been active through his role on the House Appropriations Committee in urging additional funding for autism research, wrote to CDC Director Julie Gerberding, M.D., M.P.H., on October 31, 2003, to express his “serious reservations” about the study published in Pediatrics. Weldon obtained CDC documents through the Freedom of Information Act, including earlier drafts of the study, e-mail communications among the investigators, and transcripts of a meeting of the study’s lead author, CDC staff members, and representatives of the vaccine industry. In his letter to Gerberding, Weldon outlined “a disturbing pattern which merits a thorough, open, timely, and independent review.” 

An early analysis of study results, completed in February 2000, found an association between thimerosal exposure and autism, whereas the final report published in Pediatrics in 2003 found no consistent association. Weldon accused the CDC of making “selective use of the data to make the associations in the earliest study disappear” and urged the agency to make the raw data available to outside investigators for independent analysis. Weldon also insinuated that there had been behind-the-scenes collusion between the CDC and vaccine manufacturers and pointed out that the lead author of the study, Thomas Verstraeten, M.D., had since left the CDC to work for pharmaceutical manufacturer GlaxoSmithKline. 

Verstraeten responded to these charges in a letter to Pediatrics, denying that the CDC had “watered down” the original study results. He suggested that the published conclusions had been misunderstood by the study’s critics. Although the study failed to yield a positive finding, it also could not be classified as a negative finding; that is, the researchers did not claim that they had proven the link between vaccines and autism to be false. Instead, the outcome was neutral, supporting the need for further study.7 A fact sheet about the study on the CDC Web site responded that the earlier positive findings were not statistically significant, and changes to the data analysis for the final report were intended to make the study design more rigorous, based on suggestions from outside scientific reviewers.8 It is not uncommon for a complex epidemiologic study to yield different results depending on how the data are analyzed and as more data become available over time. Thus, no evidence exists of malicious data manipulation here. Nevertheless, given the controversial nature of the study and the inconsistency of the results, further investigation was warranted. 

As a result, the CDC asked the Institute of Medicine’s Immunization Safety Review Committee to review the issue again, three years after its first review. On February 9, 2004, the committee heard a series of presentations by experts summarizing the relevant science. This was, however, no ordinary scientific meeting. The day opened with an address by Congressman Weldon, who proposed that the CDC had a “built-in conflict of interest” about vaccine safety because of its dual responsibilities to promote vaccination to prevent disease in the population and to monitor the safety of vaccines. Therefore, Weldon suggested the CDC might be reluctant to publicize an unfavorable safety report because it could lead to lower vaccination rates and damage public confidence in vaccination programs. 

The Institute of Medicine committee released its report in May 2004, based on findings from the February meeting. Their conclusions went a step further than their previous review, stating that “the committee concludes that the evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism.” Thus, although the committee’s first report in 2001 had been neutral, acknowledging the lack of evidence on the question, the new report, based on recent epidemiologic studies, including the CDC study, frankly concluded that the evidence suggests that vaccines do not cause autism. The committee did outline areas for additional research, but they urged that no policy changes about standard childhood vaccination guidelines were warranted.9 

A CHALLENGE FROM BRITAIN

On February 20, 2004, a further blow was dealt to the vaccine-autism theory when the Lancet released a statement describing “serious allegations of research misconduct” in connection with the 1998 paper by Wakefield and his colleagues. The Lancet dismissed as unsubstantiated three of the six allegations, which challenged the ethical approval of the study and the researchers’ methods of recruiting subjects. But the remaining three allegations detailed how Wakefield received £55,000 from the United Kingdom Legal Aid Board to conduct a pilot study to evaluate whether scientific evidence was available to support legal action on behalf of parents of allegedly vaccine-damaged children. Some of the children in the pilot study also appeared as subjects in Wakefield’s 1998 paper in the Lancet. The Legal Aid Board is a body of the British government that provides funding to evaluate and initiate civil actions. The Lancet noted that Wakefield had not disclosed this funding or his dual role as scientist and hired expert to find evidence for potential litigation. 

On February 20, 2004, a further blow was dealt to the vaccine-autism theory when the Lancet released a statement describing “serious allegations of research misconduct” in connection with the 1998 paper by Wakefield and his colleagues. 

Although the work published in the Lancet was a different project from that funded by the Legal Aid Board, the Lancet statement asserted that the editors should have been informed of this potential conflict. Richard Horton, M.D., editor of the Lancet, put it bluntly in speaking to the press. He told the British Broadcast Corporation that the researchers had a “fatal conflict of interest” and that, if the conflict had been disclosed, the article probably would have been rejected by Lancet

The Lancet’s press release did not mention from where or whom the “allegations” came. Two days earlier, however, the London Sunday Times medical muckraking journalist Brian Deer had met with Horton and other staff members from the Lancet to brief them on his investigation of the Wakefield study. Deer’s investigative piece appeared in print the following Sunday with the headline “Revealed: MMR research scandal.” In the article, Deer quoted Richard Smith, M.D., editor of the British Medical Journal, who said: “That MMR paper is the best example there has ever been of a very, very dodgy paper that has created a lot of discomfort and misery.” 

Then, on March 4, 2004, the Lancet published a retraction submitted by 10 of the original 13 authors of the 1998 Wakefield paper. Curiously, they did not actually retract any claim that was made in the original paper. Instead, they addressed claims attributed to it later by others. They stood by the paper’s original identification of an intestinal lesion in a number of autistic children but stated, “We wish to make it clear that in this paper no causal link was established between MMR vaccine and autism as the data were insufficient.” In the original paper, the authors had been careful to state that they had not proved the existence of such a link. But the authors of the retraction were concerned that the use of the paper by those claiming a link had brought substantial negative consequences for public health.

The retraction was not signed by Wakefield or coauthor Peter Harvey, M.D. Another coauthor, John Linnell, Ph.D., could not be located. Wakefield responded in the same issue of the journal, insisting that the study had been conducted wholly independently of the Legal Aid Board inquiry and that he had no way of knowing at the time which children were involved in the developing litigation. Interestingly, the Legal Aid Board (now called the Legal Services Commission) ended its funding of MMR litigation last year because of the lack of a conclusive link between the vaccine and autism.

PUBLIC HEALTH AND SCIENCE POLITICS

What effect has all this debate had on public opinion about the value of vaccination relative to the potential risks? A group of officials from the U.S. Department of Health and Human Services conducted a survey to find out. They questioned parents who reported the diagnosis of autism in their child to the Vaccine Adverse Event Reporting System (VAERS) from 1990 to 2001. VAERS is a voluntary registry managed by the FDA and CDC to collect information about injuries that might be vaccine related. They hypothesized that parents naturally seek explanations when a serious illness is diagnosed in their child, such as autism, and that media reports about autism and vaccines could provide a hook for them to latch on to. 

Indeed, the survey found that parents who responded to it after the Wakefield study was publicized were more likely to cite the MMR vaccine as a contributing factor to their child’s autism. Additionally, parents who reported autism to the VAERS said that they trusted advocacy groups and research organizations (such as Cure Autism Now) more than they trusted the CDC, and they shared a low opinion of the benefits of vaccination, compared with the general population. Although 84 percent of the general population believed that government immunization requirements protected their children from disease, only 34 percent of the parents who reported autism to the VAERS believed this. Similarly, although 71 percent of the general population agreed that vaccines are “always proven to be very safe” before they are approved for use, only 7 percent of VAERS reporters believed this.10 

In times of controversy, decision makers turn to scientists for an objective guide to making decisions. But in this debate over childhood vaccines and neurologic disorders, we see how the results of science can be contested when groups with different interpretations have a stake in the outcome. 

In times of controversy, decision makers turn to scientists for an objective guide to making decisions. But in this debate over childhood vaccines and neurologic disorders, we see how the results of science can be contested when groups with different interpretations have a stake in the outcome. Must we conclude, at least here, that science failed as a guide to decision making? 

Science properly conducted is driven by data, critical analysis, and unhindered inquiry by autonomous investigators. But science does not bring immediate certainty. It is a dynamic process of formulating hypotheses, subjecting them to empirical tests, and evaluating competing explanations. The scientific conclusions that best fit today’s data can be challenged by tomorrow’s new data, and science fails when it clings to a favorite theory in the teeth of new evidence that contradicts it or reveals its limitations. Certainty is especially elusive when science tries to prove a negative. A study can provide evidence of an effect, but failure to find any effect is the only logical means of demonstrating its absence, and absence leaves no footprints. Thus, the latest report of the Immunization Safety Review Committee concluded inconclusively that “the evidence favors a rejection” of the claim that thimerosal-containing vaccines cause autism, but it had to stop short of declaring the absence of an effect. 

In some cases, parents, policymakers, and courts do not have the luxury of waiting for all the evidence to come in. In making a decision about whether to vaccinate a child or to remove a suspicious substance from vaccine products, decisions must be made on the best available evidence. Thus, the Public Health Service advocated the removal of thimerosal from vaccines as a precautionary measure based on limited evidence. 

Few medications are without some risks, and controversy over vaccine policy is nothing new. Such policy has been the focus of public and political debate since the first widespread use of Edward Jenner’s smallpox vaccine in 1798. The evidence for public health benefits from vaccination is overwhelming, and, since Jenner’s day, vaccines have saved millions of lives. If vaccine policies and courtroom decisions over alleged vaccine injuries are to be based on scientific evidence that means accounting for all available evidence at a given time, including new evidence that changes earlier hypotheses. 

Although the Institute of Medicine committee was right to voice the need for investigation after some early reports about thimerosal, the committee did alter its conclusions as new evidence became available. Similarly, those who seized initial conclusions, using them to make their case, whether in courts of law or public opinion, accepted the scientific process and implied their willingness to abide by its results. They have an obligation to follow the weight of the evidence in whichever direction it leads. It remains to be seen to what degree science will be permitted to inform the ongoing lawsuits over childhood vaccines and autism. But if the system functions properly, cases lacking sufficient evidence of a causal connection will not proceed. 

The real lesson is that those who make use of science must remain open to altering their conclusions as new evidence becomes available. 

The lesson of the story of autism and vaccines is not that science failed us. Science is a method of reaching the only kind of certainty that we can attain—not automatically or immediately, but ultimately with an extremely impressive record of success. The real lesson is that those who make use of science must remain open to altering their conclusions as new evidence becomes available. Science is not made from a particular theory or hypothesis. It is a collection of methods and a process for understanding the world around us. If science cannot always deliver the certainty that some would like, it nonetheless brings us ever closer to truth.

References

  1. Kanner, L. “Autistic disturbances of affective contact.” Nervous Child 1943; 2: 217-250.
  2. US Department of Education. “Twenty-sixth Annual Report to Congress on the Implementation of the Individuals with Disabilities Education Act. To Assure the Free Appropriate Public Education of All Children with Disabilities.” Washington, DC. US Department of Education, 2003: Section 618.
  3. California Department of Developmental Services. “Autism Spectrum Disorders. Changes in the California Caseload. An Update: 1999 through 2002.” Sacramento, CA. Department of Developmental Services, 2003. http://www.dds.ca.gov/autism/pdf/ AutismReport2003.pdf (accessed September, 2004).
  4. Wakefield, AJ, Murch, SH, Anthony, A, et al. “Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorder in children.” Lancet 1998; 351: 637641. Retraction: Murch, SH, Anthony, A, Casson, DH, et al. Lancet 2004; 363: 750.
  5. Chen, RT, and DeStefano, F. “Vaccine adverse events: causal or coincidental?” Lancet 1998: 351: 611-612.
  6. Center for Disease Control. “Joint Statement (concerning Thimerosal) of the American Academy of Pediatrics (AAP) and the U.S. Public Health Service (PHS).” July 7, 1999. http://www.cdc.gov/nip/vacsafe/concerns/ thimerosal/thimerosal-AAP&PHS.htm (accessed September, 2004).
  7. Verstraeten, T. “Thimerosal, the Centers for Disease Control and Prevention, and Glaxo-SmithKline.” [letter] Pediatrics 2004; 113: 932.
  8. Center for Disease Control. “CDC Research on the Safety of Thimersol Containing Vaccines.” http://www.cdc.gov/nip/vacsafe/concerns/ thimerosal/researchQAs.htm#vsdres (accessed September, 2004). 
  9. National Academy of Science. Immunization Safety Review: Vaccines and Autism. National Academic Press, 2004. http://www.nap.edu/books/030909237X/html/ (accessed September, 2004).
  10. Woo, EJ, Ball R, Bostrom A, et. al. “Vaccine risk perception among reporters of autism after vaccination: Vaccine Adverse Event Reporting System 1990-2001.” American Journal of Public Health 2004; 94: 990-995.



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Scientific Advisory Board
Joseph T. Coyle, M.D., Harvard Medical School
Kay Redfield Jamison, Ph.D., The Johns Hopkins University School of Medicine
Pierre J. Magistretti, M.D., Ph.D., University of Lausanne Medical School and Hospital
Robert Malenka, M.D., Ph.D., Stanford University School of Medicine
Bruce S. McEwen, Ph.D., The Rockefeller University
Donald Price, M.D., The Johns Hopkins University School of Medicine

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