IOM press release, for reference

Date: May 18, 2004

Contacts: Christine Stencel, Media Relations Officer
Chris Dobbins, Media Relations Assistant
Office of News and Public Information
202-334-2138; e-mail news@nas.edu  

FOR IMMEDIATE RELEASE

MMR Vaccine and Thimerosal-Containing Vaccines Are Not Associated With Autism, IOM Report Says

Furthermore, the hypotheses regarding how the MMR vaccine and thimerosal could trigger autism lack supporting evidence and are theoretical only.

Further research to find the cause of autism should be directed toward other lines of inquiry that are supported by current knowledge and evidence and offer more promise for providing an answer, said the committee that wrote the report.

"The overwhelming evidence from several well-designed studies indicates that childhood vaccines are not associated with autism," said committee chair Marie McCormick, Sumner and Esther Feldberg Professor of Maternal and Child Health, Harvard School of Public Health, Boston. "We strongly support ongoing research to discover the cause or causes of this devastating disorder. Resources would be used most effectively if they were directed toward those avenues of inquiry that offer the greatest promise for answers. Without supporting evidence, the vaccine hypothesis does not hold such promise."

The report updates two earlier IOM reports, published in 2001, on possible links between autism and the MMR vaccine and thimerosal. At that time, the committee determined that the evidence did not show an association between the MMR vaccine and autism, but there was not enough evidence to determine whether thimerosal was associated with neurodevelopmental disorders such as autism. Given that mercury is known to have a toxic effect on the nervous system and that prenatal exposures to another form of mercury have been shown to adversely affect early childhood development, the committee concluded in 2001 that it was possible to hypothesize that thimerosal might trigger neurodevelopmental problems. The committee revisited these issues because several studies exploring the epidemiology and biological mechanisms of possible links between vaccines and autism have been undertaken during the past three years.

The committee based its latest conclusions and recommendations on a careful review of the literature it had assessed to develop its previous reports; subsequent studies; and other information provided by researchers, parents, and others. Epidemiological studies that looked at autism rates and exposures to vaccines carried the most weight in the committee's assessment of causality, but it considered other kinds of studies as well.

Five large epidemiological studies conducted in the United States, the United Kingdom, Denmark, and Sweden since 2001 consistently provided evidence that there is no association between thimerosal-containing vaccines and autism. Similarly, 14 large epidemiological studies consistently showed no association between the MMR vaccine and autism. The committee also reviewed five studies that reported links between thimerosal and autism and two that indicated a connection between the MMR vaccine and the disorder. However, limitations in how these studies were conducted and how the data were analyzed led the committee to conclude that they did not provide evidence supporting an association between vaccines and autism.

The committee also reviewed evidence related to possible biological mechanisms by which immunizations might trigger autism. For example, it has been hypothesized that the measles virus in the MMR vaccine might lodge in the intestines and trigger the release of toxins that lead to autism.

Another hypothesis suggests that the MMR vaccine might stimulate the release of immune factors that damage the central nervous system, resulting in autism. It also has been suggested that thimerosal may interfere with biochemical systems in the brain, leading to the disorder.

However, no evidence has yet been found that the immune system or its activation play a direct role in causing autism, the report notes. Autism also has never been documented as a consequence of exposure to high doses of mercury. While the committee agreed that the studies exploring these hypotheses raise interesting questions, they do not address the specifics of how autism could result. Therefore, evidence for any biological mechanism linking vaccines with autism can only be considered theoretical.

Autism is not a single condition, but rather a complex set of severe developmental disorders -- also referred to as autistic spectrum disorders -- characterized by sustained impairments in social interaction and communication abilities, as well as restricted or repetitive patterns of behaviors and interests. It is unclear how many cases of autism there are, but two reviews of published studies put the prevalence at one case for every 1,000 children. While some information suggests that autism rates may be rising, it is not clear whether the observed increase is real or due to factors such as heightened awareness of the disorder or the use of a broader diagnostic definition.

Thimerosal is an organic mercury compound that is still used as a preservative in some adult vaccines. It began to be removed from vaccines for children in 1999, and as of mid-2000, vaccines that are recommended for universal use in infants and young children are available in forms that have no or only trace amounts of thimerosal.

This study is the eighth and final in a series on vaccine safety sponsored by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases. The Institute of Medicine is a private, nonprofit institution that provides health policy advice under a congressional charter granted to the National Academy of Sciences.

A committee roster follows.

Pre-publication copies of Immunization Safety Review: Vaccines and Autism are available from the National Academies Press; tel. 202-334-3313 or 1-800-624-6242 or on the Internet at http://www.nap.edu. Reporters may obtain a copy from the Office of News and Public Information (contacts listed above).

[ This news release and report are available at http://national-academies.org ]

INSTITUTE OF MEDICINE

Board on Health Promotion and Disease Prevention
Immunization Safety Review Committee

Marie C. McCormick, M.D., Sc.D. (chair)
Sumner and Esther Feldberg Professor of Maternal and Child Health
Department of Society, Human Development and Health
Harvard School of Public Health, Boston

Ronald Bayer, Ph.D., Professor
Department of Sociomedical Sciences
Joseph L. Mailman School of Public Health
Columbia University
New York City

Alfred Berg, M.D., M.P.H.
Professor and Chair
Department of Family Medicine
University of Washington School of Medicine, Seattle

Rosemary Casey, M.D.
Associate Professor of Pediatrics
Jefferson Medical College, and
Director of Lankenau Faculty Pediatrics
Wynnewood, Pa.

Betsy Foxman, Ph.D., Professor
Department of Epidemiology
School of Public Health
University of Michigan, Ann Arbor

Constantine Gatsonis, Ph.D.
Professor of Medical Science and Applied Mathematics, and
Director, Center for Statistical Sciences
Brown University, Providence, R.I.

Steven Goodman, M.D., M.H.S., Ph.D., Associate Professor
Department of Oncology, Division of Biostatistics
School of Medicine, Johns Hopkins University, Baltimore

Ellen Horak, M.S.N., Education and Nurse Consultant
Public Management Center, University of Kansas, Topeka

Michael Kaback, M.D., Professor of Pediatrics and Reproductive Medicine
University of California, San Diego

Gerald Medoff, M.D., Professor
Department of Internal Medicine
Washington University School of Medicine, St. Louis

Rebecca Parkin, Ph.D.
Associate Professor of Environmental and Occupational Health, Epidemiology
and Biostatistics, and Associate Dean for Research and Public Health Practice
School of Public Health and Health Services
George Washington University, Washington, D.C.

Bennett A. Shaywitz, M.D., Professor of Pediatrics and Neurology
Yale University School of Medicine, and
Co-Director, Yale Center for the Study of Learning and Attention
New Haven, Conn.

Christopher Wilson, M.D., Professor and Chair
Department of Immunology, University of Washington, Seattle

INSTITUTE STAFF
Kathleen Stratton, Ph.D., Study Director
Immunization Safety Review: Vaccines and Autism
Institute of Medicine

Telephone Briefing

May 18, 2004

Opening Statement by Marie C. McCormick, M.D., Sc.D.

Good afternoon. On behalf of the Institute of Medicine and the entire committee, I would like to welcome reporters and guests to the release of our report, Vaccines and Autism. I am joined by fellow committee member Steven Goodman.

The Committee on Immunization Safety Review was established in January 2001 in response to a request from the Centers for Disease Control and Prevention and the National Institutes of Health, both of which recognized the need for an independent group of scientists to address growing concerns about vaccine safety in a timely and objective manner. The committee consists of 13 members with expertise in a variety of relevant public health and medical disciplines.

Since its inception, the committee has issued seven reports. In this eighth and final report, we were asked to revisit concerns about vaccines and autism, specifically whether the vaccine preservative thimerosal or the measles-mumps-rubella -- or MMR -- vaccine are causally related to autism.

The current report follows up two reports examining the role of vaccines in autism that the committee issued in 2001. One reviewed the hypothesized causal association between the MMR vaccine and autism, which the committee rejected based on the evidence at the time. The second report reviewed the hypothesized link between thimerosal-containing vaccines and a broad range of neurodevelopmental disorders including autism. The committee concluded that the evidence available at the time was inadequate to accept or reject a causal relationship between thimerosal and neurodevelopmental disorders.

The report we are releasing today incorporates new epidemiological evidence and studies of biological mechanisms related to vaccines and autism that have emerged since the earlier reports. The committee wishes to emphasize that this report focuses only on autism and does not address other neurodevelopmental disorders.

Scientists generally agree that most cases of autism likely result from events in the prenatal period or shortly after birth. But there are concerns about the MMR vaccine because autistic symptoms typically do not emerge until the child's second year of life, which is about the same time that the MMR vaccine is first administered. In addition, some point to the apparent increase in the number of reported cases of autism, and question whether this rise may be due, in part, to widespread use of the MMR vaccine and thimerosal-containing vaccines.

Thimerosal has been used as a preservative to prevent bacterial contamination in multidose vials of several childhood and adult vaccines.

The active ingredient in thimerosal is ethylmercury, a close chemical relative of methylmercury. Many forms of mercury are known to damage the nervous system in high doses, although ethylmercury has been studied less than other forms of mercury. In 1999 thimerosal began to be removed from vaccines. This action was taken as a precaution to decrease mercury exposures, despite the absence of data at that time to suggest that thimerosal was in fact dangerous at the levels present in vaccines. As of mid-2000, all childhood vaccines recommended for universal use were available free of thimerosal as a preservative.

On the issue of whether thimerosal is associated with autism, epidemiological studies in the United States, the United Kingdom, Denmark, and Sweden that have been published since our earlier study provided significant evidence that there is no association between thimerosal-containing vaccines and autism. Based on these studies, the committee concluded that the evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism.

To assess whether the MMR vaccine is associated with autism, the committee looked at the large number of epidemiological studies that have examined this issue. Let me note that the MMR vaccine does not contain and has never contained thimerosal. Fourteen large, well-designed epidemiological studies consistently showed no association between the MMR vaccine and autism.

Based on this body of evidence, the committee saw no reason to change its 2001 conclusion that the evidence favors rejection of a causal relationship between the MMR vaccine and autism.

The committee also reviewed the potential biological mechanisms that have been put forth as possible explanations for how vaccines might cause autism. These hypothesized mechanisms include:

-- The release of chemicals into the brain due to disruption of intestinal function by the MMR vaccine.

-- Triggering of abnormalities in the immune system that are indicative of damage to the central nervous system induced by vaccines.

-- Increased accumulation of mercury and decreased excretion of the element from the brains of a subgroup of children.

-- The effects of thimerosal on a variety of biochemical pathways.

The evidence offered for these various hypotheses includes data from in vitro experimental systems, clinical observations, and analogies between rodent behavior and human behavior. While the laboratory observations of the toxic effects of mercury are important in understanding how this metal may cause damage, these observations do not explain how specific exposures in a rapidly developing infant affect certain tissues but not others where these mechanisms are also active. The laboratory studies also have not

shown how these effects lead to autism. The committee does not dispute that mercury-containing compounds, including thimerosal, can be very damaging to the nervous system. The question is whether these damaging effects are related to the development of autism.

While the committee agreed that the studies raise interesting questions, they do not address the specifics of how these mechanisms result in the symptoms of autism. It is difficult to establish a link between vaccine components and this disorder because scientific understanding about the causes of autism is only in an early stage. Autism is not a single condition but rather a complex set of disorders. It is possible, and perhaps even likely, that autism will be found to have many different causes. It is possible that some people with autism also have abnormal immune reactions, or abnormalities in the way they metabolize mercury. But it is also possible that vaccination does not cause these abnormalities, and likewise that the abnormalities do not lead to autism.

In the absence of experimental or human evidence that either the MMR vaccine or vaccines containing thimerosal affect metabolic, developmental, immune, or other physiological or molecular mechanisms that are causally related to the development of autism, the committee concludes that the hypotheses generated to date are theoretical only.

The committee recommends a public health response that fully supports an array of vaccine safety activities. While the committee strongly supports research that focuses on achieving a better understanding of autism, we recommend that future research be directed toward other lines of inquiry that are supported by current knowledge and evidence, and that offer more promise for finding an answer. Given the current evidence, the vaccine hypothesis doesn't offer that promise.

The committee also believes that communication with the public about vaccine safety issues needs to be improved. To that end, we recommend developing programs to increase public participation in research on vaccine safety and in policy decisions about the issue. Efforts are also needed to enhance the skills and willingness of scientists and government officials to engage in constructive dialogue with the public about research findings and their policy implications.

This concludes my opening statement. My colleague Steven Goodman and I will now take your questions. We anticipate that there will be a lot of questions, and would like to get to as many as possible during the time remaining in this hour, so we urge you to state your questions as succinctly as possible. Thank you.

The report can be viewed at:

http://www.nap.edu/books/030909237X/html/