Thiomersal controversy
Encyclopedia
- This article uses the International Nonproprietary NameInternational Nonproprietary NameAn International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
"thiomersal", not the common U.S. spelling "thimerosal".
The thiomersal controversy describes claims that vaccines containing the mercury-based
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
preservative thiomersal
Thiomersal
Thiomersal , and commonly known in the US as thimerosal, is an organomercury compound. This compound is a well established antiseptic and antifungal agent....
contribute to the development of autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and other brain development disorders. The current scientific consensus
Scientific consensus
Scientific consensus is the collective judgment, position, and opinion of the community of scientists in a particular field of study. Consensus implies general agreement, though not necessarily unanimity. Scientific consensus is not by itself a scientific argument, and it is not part of the...
is that no convincing scientific evidence supports these claims.
Thiomersal is an organomercury
Organomercury
Organomercury refers to the group of organometallic compounds that contain mercury. Typically the Hg-C bond is stable toward air and moisture but sensitive to light. Important organomercury compounds are the methylmercury cation, CH3Hg+; ethylmercury cation, C2H5Hg+; dimethylmercury, 2Hg,...
compound used as a preservative in vaccines since the 1930s to prevent bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l and fungal contamination. Following a mandated review of mercury-containing food and drugs, the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics
American Academy of Pediatrics
The American Academy of Pediatrics is the major professional association of pediatricians in the United States. The AAP was founded in 1930 by 35 pediatricians to address pediatric healthcare standards. It currently has 60,000 members in primary care and sub-specialist areas...
(AAP) asked vaccine makers to remove thiomersal from vaccines as quickly as possible as a purely precautionary measure, and it was rapidly phased out of most U.S. and European vaccines. In the context of perceived increased autism rates and increased number of vaccines in the childhood vaccination schedule, some parents believed the action to remove thiomersal as an indication that the preservative caused autism.
The potential impact of thiomersal on autism has been investigated extensively. Multiple lines of scientific evidence have shown that thiomersal does not cause autism. For example, the clinical symptoms of mercury poisoning
Mercury poisoning
Mercury poisoning is a disease caused by exposure to mercury or its compounds. Mercury is a heavy metal occurring in several forms, all of which can produce toxic effects in high enough doses...
differ significantly from those of autism. In addition, multiple population studies have found no association between thiomersal and autism, and rates of autism have continued to increase despite removal of thiomersal from vaccines. Thus, major scientific and medical bodies such as the Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
and World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) as well as governmental agencies such as the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) and the CDC reject any role for thiomersal in autism or other neurodevelopmental disorders. In spite of the consensus of the scientific community, some parents and advocacy groups continue to contend that thiomersal is linked to autism.
This controversy has caused harm due to parents attempting to treat their autistic children with unproven and possibly dangerous treatments, discouraging parents from vaccinating their children due to fears about thiomersal toxicity and diverting resources away from research into more promising areas for the cause of autism. Thousands of lawsuits have been filed in the U.S. to seek damages from alleged toxicity from vaccines, including those purportedly caused by thiomersal. US courts have ruled against multiple representative test cases involving thiomersal, suggesting the majority are unlikely to succeed.
History
Thiomersal was introduced as a preservative in the 1930s to prevent the growth of infectious organisms such as bacteria and fungi, and has been in use in vaccines and other products such as immunoglobulinAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
preparations and ophthalmic and nasal solutions. Vaccine manufacturers have used preservatives to prevent microbial growth during the manufacturing process or when packaged as "multi-dose" products to allow for multiple punctures of the same vial to dispense multiple vaccinations with less fear of contamination. After the FDA Modernization Act of 1997
Food and Drug Administration Modernization Act of 1997
The United States Food and Drug Administration Modernization Act of 1997 amended the Federal Food, Drug, and Cosmetic Act. This act is related to the regulation of food, drugs, devices, and biological products by the FDA. These changes were made in order to recognize the changes in the way the...
mandated a review and risk assessment of all mercury-containing food and drugs, vaccine manufacturers responded to FDA requests made in December 1998 and April 1999 to provide detailed information about the thiomersal content of their preparations.
A review of the data showed that while the vaccine schedule for infants did not exceed FDA, Agency for Toxic Substances and Disease Registry
Agency for Toxic Substances and Disease Registry
The Agency for Toxic Substances and Disease Registry is a federal public health agency within the United States Department of Health and Human Services. The agency focuses on minimizing human health risks associated with exposure to hazardous substances...
(ATSDR), or WHO guidelines on mercury exposure, it could have exceeded Environmental Protection Agency (EPA) standards for the first six months of life, depending on the vaccine formulation and the weight of the infant. The review also highlighted difficulty interpreting toxicity of the ethylmercury
Ethylmercury
Ethylmercury is a cation composed of an ethyl group bound to a mercury centre; its chemical formula is C2H5Hg+...
in thiomersal because guidelines for mercury toxicity were based primarily on studies of methylmercury
Methylmercury
Methylmercury is an organometallic cation with the formula . It is a bioaccumulative environmental toxicant.-Structure:...
, a different mercury compound with different toxicologic properties. Multiple meetings were scheduled among various government officials and scientists from multiple agencies to discuss the appropriate response to this evidence. There was a wide range of opinions on the urgency and significance of the safety of thiomersal, with some toxicologists suggesting there was no clear evidence that thiomersal was harmful and other participants like Dr. Neal Halsey
Neal Halsey
Neal A. Halsey, MD , is a pediatrician, with subspecialty training in infectious diseases, international health and epidemiology. Currently, Dr...
, director of the Institute of Vaccine Safety, strongly advocating removal of thiomersal from vaccines due to possible safety risks. In the process of forming the response to this information, the participants attempted to strike a balance between acknowledging possible harm from thiomersal and the actual risks involved if childhood vaccinations were delayed or stopped.
Upon conclusion of their review, the FDA, in conjunction with the other members of the US Public Health Service (USPHS), the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(NIH), CDC and Health Resources and Services Administration
Health Resources and Services Administration
The Health Resources and Services Administration , is an agency of the U.S. Department of Health and Human Services located in Rockville, Maryland...
(HRSA), in a joint statement with the AAP in July 1999 concluded that there was "no evidence of harm caused by doses of thimerosal found in vaccines, except for local hypersensitivity reactions."
Despite the lack of convincing evidence of toxicity of thiomersal when used as a vaccine preservative, the USPHS and AAP determined that thiomersal should be removed from vaccines as a purely precautionary measure. This action was based on the precautionary principle
Precautionary principle
The precautionary principle or precautionary approach states that if an action or policy has a suspected risk of causing harm to the public or to the environment, in the absence of scientific consensus that the action or policy is harmful, the burden of proof that it is not harmful falls on those...
, which assumes that there is no harm in exercising caution even if it later turns out to be unnecessary. The CDC and AAP reasoned that despite the lack of evidence of significant harm in the use of thiomersal in vaccines, the removal of this preservative would increase the public confidence in the safety of vaccines. Although thiomersal was largely removed from routine infant vaccines by summer 2001 in the U.S., some vaccines continue to contain non-trace amounts of thiomersal, mainly in multi-dose vaccines targeted against influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
and tetanus
Tetanus
Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...
.
Rationale for concern
Minamata disease
', sometimes referred to as , is a neurological syndrome caused by severe mercury poisoning. Symptoms include ataxia, numbness in the hands and feet, general muscle weakness, narrowing of the field of vision and damage to hearing and speech. In extreme cases, insanity, paralysis, coma, and death...
and in the 1970s in Iraq from fungicide contamination of wheat. These incidents led to new research on methylmercury safety and culminated in the publication of an array of confusing recommendations by public health agencies in the 1990s warning against methylmercury exposure in adults and pregnant women, which ensured a continued high public awareness of mercury toxicity. Second, the vaccine schedule for infants expanded in the 1990s to include more vaccines, some of which, including the Hib vaccine
Hib vaccine
Haemophilus influenzae type B vaccine is a conjugate vaccine developed for the prevention of invasive disease caused by Haemophilus influenzae type b bacteria. The Centers for Disease Control and Prevention has recommended the use of the Hib vaccine. Due to routine use of the Hib vaccine in...
, DTaP vaccine and hepatitis B vaccine
Hepatitis B vaccine
Hepatitis B vaccine is a vaccine developed for the prevention of hepatitis B virus infection. The vaccine contains one of the viral envelope proteins, hepatitis B surface antigen . It is produced by yeast cells, into which the genetic code for HBsAg has been inserted...
, could have contained thiomersal. Third, the number of diagnoses of autism
Epidemiology of autism
The epidemiology of autism is the study of factors affecting autism spectrum disorders . Most recent reviews of epidemiology estimate a prevalence of one to two cases per 2,000 people for autism, and about six per 1,000 for ASD; because of inadequate data, these numbers may underestimate ASD's true...
grew in the 1990s, leading parents of these children to search for an explanation for the apparent rise in diagnoses, including considering possible environmental factors. The dramatic increase in reported cases of autism during the 1990s and early 2000s is largely attributable to changes in diagnostic practices, referral patterns, availability of services, age at diagnosis, and public awareness, and it is unknown whether autism's true prevalence increased during the period. Nevertheless, some parents believed that there was a growing "autism epidemic" and connected these three factors to conclude that the increase in number of vaccines, and specifically the mercury in thiomersal in those vaccines, were causing a dramatic increase in the incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
of autism.
Advocates of a thiomersal-autism link also relied on indirect evidence from the scientific literature, including analogy with neurotoxic effects of other mercury compounds, the reported epidemiologic association between autism and vaccine use, and extrapolation from in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
experiments and animal studies. Studies conducted by Mark Geier
Mark Geier
Mark R. Geier is a self-employed American physician and controversial professional witness who has testified in more than 90 cases regarding allegations of injury or illness caused by vaccines....
and his son David Geier have been the most frequently cited research by parents advocating a link between thiomersal and autism. This research by Geier has received considerable criticism for methodological problems in his research, including not presenting methods and statistical analyses to others for verification, improperly analyzing data taken from Vaccine Adverse Event Reporting System
Vaccine Adverse Event Reporting System
The Vaccine Adverse Event Reporting System is a United States program for vaccine safety, co-managed by the Centers for Disease Control and Prevention and the Food and Drug Administration . VAERS is a post-marketing safety surveillance program, collecting information about adverse events that...
, as well as either mislabelling or confusing fundamental statistical terms in his papers, leading to results that were "uninterpretable".
Publicity of concern
Several months after the recommendation to have thiomersal removed from vaccines was published, a speculative article was published in Medical HypothesesMedical Hypotheses
Medical Hypotheses is a medical journal published by Elsevier. It was originally intended as a forum for unconventional ideas without the traditional filter of scientific peer review, "so long as are coherent and clearly expressed" in order to "foster the diversity and debate upon which the...
, a non-peer-reviewed
Peer review
Peer review is a process of self-regulation by a profession or a process of evaluation involving qualified individuals within the relevant field. Peer review methods are employed to maintain standards, improve performance and provide credibility...
journal, by parents who launched the parental advocacy group SafeMinds
SafeMinds
The Coalition for SafeMinds is a non-profit organization dedicated to investigating the risks of exposure to mercury from medical products...
to promote the theory that thiomersal caused autism. The controversy began to gain legitimacy in the eyes of the public from this foundation, and gained widening support within certain elements in the autism advocacy community as well as in the political arena, with U.S. Representative Dan Burton
Dan Burton
Danny "Dan" Lee Burton is the U.S. Representative for , and previously the , serving since 1983. He is a member of the Republican Party....
openly supporting this movement and holding a number of Congressional hearings on the subject.
Further support for the association between autism and thiomersal appeared in an article by Robert F. Kennedy, Jr.
Robert F. Kennedy, Jr.
Robert Francis Kennedy, Jr. is an American radio host, activist, and attorney specializing in environmental law. He is the third of eleven children born to Ethel Skakel Kennedy and Robert F. Kennedy and is the nephew of John F. Kennedy and Edward M. Kennedy...
in the magazines Rolling Stone
Rolling Stone
Rolling Stone is a US-based magazine devoted to music, liberal politics, and popular culture that is published every two weeks. Rolling Stone was founded in San Francisco in 1967 by Jann Wenner and music critic Ralph J...
and Salon.com
Salon.com
Salon.com, part of Salon Media Group , often just called Salon, is an online liberal magazine, with content updated each weekday. Salon was founded by David Talbot and launched on November 20, 1995. It was the internet's first online-only commercial publication. The magazine focuses on U.S...
alleging a government conspiracy at a CDC meeting to conceal the dangers of thiomersal to protect the pharmaceutical industry, and a book written by David Kirby, Evidence of Harm, dramatizing the lives of parents of autistic children, with both authors participating in media interviews to promote their work and the controversy. Although the allegations by Kennedy were denied and a US Senate committee investigation later found no evidence to substantiate the most serious allegations, the story had already been well publicized by leveraging Kennedy's celebrity. Salon magazine subsequently amended Kennedy's article five times due to factual errors and later retracted it completely on January 16th, 2011, stating that the works of critics of the article and evidence of the flaws in the science connecting autism and vaccines undermined the value of the article to the editors.
Meanwhile, during this time of increased media publicity of the controversy, public health officials and institutions did little to rebut the concerns and speculative theories being offered. Media attention and polarization of the debate has also been fueled by personal injury lawyer
Personal injury lawyer
A personal injury lawyer is a lawyer who provides legal representation to those who claim to have been injured, physically or psychologically, as a result of the negligence or wrongdoing of another person, company, government agency, or other entity....
s who took out full-page ads in prominent newspapers and offered financial support for expert witness
Expert witness
An expert witness, professional witness or judicial expert is a witness, who by virtue of education, training, skill, or experience, is believed to have expertise and specialised knowledge in a particular subject beyond that of the average person, sufficient that others may officially and legally...
es who dissented from the scientific consensus that there is no convincing evidence for a link between thiomersal and autism. Paul Offit
Paul Offit
Paul A. Offit, M.D., is an American pediatrician specializing in infectious diseases and an expert on vaccines, immunology, and virology. He is the co-inventor of a rotavirus vaccine that has been credited with saving hundreds of lives every day. Offit is the Maurice R...
, a leading vaccine researcher and advocate, has also noted a tendency in the media to provide false balance
False balance
False balance is a centuries old English phrase, found in the King James Bible to indicate a dishonest measurement....
by perpetually presenting both sides of an issue even when only one side is supported by the evidence and thereby giving a platform for the spread of misinformation.
Despite the consensus from experts that there is no link between thiomersal and autism, many parents continue to hold on to their belief that such a link exists. These parents share the viewpoint that autism is not just treatable, but curable through "biomedical" interventions and have been frustrated by the lack of progress from more "mainline" scientists in finding this cure. Instead, they have supported an alternative community of like-minded parents, physicians and scientists who promote this belief. This mindset has taught these parents to challenge the expertise from the mainstream scientific community. Parents have also been influenced by a large number of online anti-vaccination websites that present themselves as an alternative source for evidence using pseudoscientific claims. These websites use emotional appeals to gather support and frame the controversy as an adversarial dispute between parents and a conspiracy of doctors and scientists. Advocates for a thiomersal-autism link have also relied on celebrities like model Jenny McCarthy
Jenny McCarthy
Jennifer Ann "Jenny" McCarthy is an American model, comedian, actress, author, activist, and game show host. She began her career in 1993 as a nude model for Playboy magazine and was later named their Playmate of the Year. McCarthy then parlayed her Playboy fame into a successful television and...
and information presented on Don Imus'
Don Imus
John Donald "Don" Imus, Jr. is an American radio host, humorist, philanthropist and writer. His nationally-syndicated talk show, Imus in the Morning, is broadcast throughout the United States by Citadel Media and relayed on television by the Fox Business Network.-Personal life:Imus was born in...
Imus in the Morning
Imus in the Morning
Imus in the Morning is an American radio show hosted by Don Imus on Cumulus Media Networks , and simulcast for television on Fox Business Network....
radio show to persuade the public to their cause, instead of relying only on "dry" scientific papers and scientists. McCarthy has published a book describing her personal experience with her autistic son and appeared on The Oprah Winfrey Show
The Oprah Winfrey Show
The Oprah Winfrey Show is an American syndicated talk show hosted and produced by its namesake Oprah Winfrey. It ran nationally for 25 seasons beginning in 1986, before concluding in 2011. It is the highest-rated talk show in American television history....
to promote the hypothesis of vaccines causing autism. Bitterness over this issue has led to numerous threats made against the CDC, with increased security put in place in response to these threats as well as researchers like Offit.
Rationale for doubting link
Various lines of evidence undermine a proposed link between thiomersal and autism. For example, although advocates of a thiomersal-autism link consider autism a form of "mercury poisoning," the typical symptoms of mercury toxicity are significantly different than symptoms seen in autism. Likewise, the neuroanatomicNeuroanatomy
Neuroanatomy is the study of the anatomy and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defined nervous systems, and thus we can begin to speak of...
and histopathologic
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
features of the brains of patients who have mercury poisoning, both with methylmercury as well as ethylmercury, have significant differences from the brains of people with autism. Previous episodes of widespread mercury toxicity in a population such as in Minamata Bay
Minamata Bay
Minamata is a small factory town. Minamata Bay is a bay on the west coast of Kyūshū island, located in Kumamoto Prefecture, Japan. The bay is part of the larger Shiranui Sea which is sandwiched between the coast of the Kyūshū mainland and the off-lying islands of Kumamoto and Nagasaki...
, Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
would also be expected to lead to documentation of a significant rise in autism or autism-like behavior in children should autism be caused by mercury poisoning. However, research on several episodes of acute and chronic mercury poisoning have not documented any such rise in autism like behavior. Although some parents cite an association between the timing of onset of autistic symptoms with the timing of vaccinations as evidence of an environmental cause such as thiomersal, this line of reasoning can be misleading. Associations such as these do not establish causation
Correlation does not imply causation
"Correlation does not imply causation" is a phrase used in science and statistics to emphasize that correlation between two variables does not automatically imply that one causes the other "Correlation does not imply causation" (related to "ignoring a common cause" and questionable cause) is a...
as the two occurring together may be only coincidental in nature. Also, genetic disorders that have no environmental triggers such as Rett syndrome
Rett syndrome
Rett syndrome is a neurodevelopmental disorder of the grey matter of the brain that almost exclusively affects females. The clinical features include small hands and feet and a deceleration of the rate of head growth . Repetitive hand movements, such as wringing and/or repeatedly putting hands into...
and Huntington's disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
nevertheless have specific ages when they begin to show symptoms, suggesting specific ages of onset of symptoms does not necessarily require an environmental cause.
Although the concern for a thiomersal-autism link was originally derived from indirect evidence based on the known potent neurotoxic effects of methylmercury, recent studies show these feared effects were likely overestimated. Ethylmercury, such as in thiomersal, clears much faster from the body after administration than methylmercury, suggesting total mercury exposure over time is much less with ethylmercury. Currently used methods of estimating brain deposition of mercury likely overestimates the amounts deposited due to ethylmercury, and ethylmercury also decomposes quicker in the brain than methylmercury, suggesting a lower risk of brain damage. These findings show that the assumptions that originally led to concern about the toxicity of ethylmercury, which were based on direct comparison to methylmercury, were flawed.
Population studies
Multiple studies have been performed on data from large populations of children to study the relationship between the use of vaccines containing thiomersal, and autism and other neurodevelopmental disorders. Almost all of these studies have found no association between thiomersal-containing vaccines (TCVs) and autism, and studies done after the removal of thiomersal from vaccines have nevertheless shown autism rates continuing to increase. The only epidemiologic research that has found a purported link between TCVs and autism has been conducted by Mark Geier, whose flawed research has not been given any weight by independent reviews.In Europe, a cohort
Cohort (statistics)
In statistics and demography, a cohort is a group of subjects who have shared a particular time together during a particular time span . Cohorts may be tracked over extended periods in a cohort study. The cohort can be modified by censoring, i.e...
study of 467,450 Danish children found no association between TCVs and autism or autism spectrum disorders (ASDs), nor any dose-response relationship
Dose-response relationship
The dose-response relationship, or exposure-response relationship, describes the change in effect on an organism caused by differing levels of exposure to a stressor after a certain exposure time...
between thiomersal and ASDs that would be suggestive of toxic exposure. An ecological
Ecological correlation
In statistics, an ecological correlation is a correlation between two variables that are group means, in contrast to a correlation between two variables that describe individuals. For example, one might study the correlation between physical activity and weight among sixth-grade children...
analysis that studied 956 Danish children diagnosed with autism likewise did not show an association between autism and thiomersal. A retrospective cohort study
Retrospective cohort study
A retrospective cohort study, also called a historic cohort study, generally means to take a look back at events that already have taken place...
on 109,863 children in the United Kingdom found no association between TCVs and autism, but a possible increased risk for tics. Analysis in this study also showed a possible protective effect with respect to general developmental disorders, attention-deficit disorder, and otherwise unspecified developmental delay. Another UK study based on a prospective cohort
Prospective cohort study
A prospective cohort study is a cohort study that follows over time a group of similar individuals who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome...
of 13,617 children likewise found more associated benefits than risks from thiomersal exposure with respect to developmental disorders. Because the Danish and UK studies involved only diphtheria-tetanus-pertussis (DTP) or diphtheria-tetanus (DT) vaccines, they are less relevant for the higher thiomersal exposure levels that occurred in the U.S.
In North America, a Canadian study of 27,749 children in Quebec showed that thiomersal was unrelated to the increasing trend in pervasive developmental disorders (PDDs). In fact, the study noted that rates of PDDs were higher in the birth cohorts with no thiomersal when compared to those with medium or high levels of exposure. A study performed in the US which analyzed data from 78,829 children enrolled in HMOs taken from the Vaccine Safety Datalink
Vaccine Safety Datalink
The Vaccine Safety Datalink Project was established in 1990 by the United States Centers for Disease Control and Prevention to study the adverse side effects of vaccines....
(VSD) did not show any consistent association between TCVs and neurodevelopmental outcomes, noting different results from data in different HMOs. Another study which studied children enrolled in HMOs that participated in the VSD found no evidence of a causal relationship between early exposure to mercury such as from thiomersal and deficits in neuropsychological functioning, although the authors did not address autism specifically. A later study performed in the same HMO groups found no increased risk of autism or autism spectrum disorders with increased exposure to thiomersal in early life from vaccines or immunoglobulins, and actually found decreased risk for ASDs with increased ethylmercury exposure when adjusting for covariate
Covariate
In statistics, a covariate is a variable that is possibly predictive of the outcome under study. A covariate may be of direct interest or it may be a confounding or interacting variable....
s in certain exposure periods. A study performed in California found that removal of thiomersal from vaccines did not decrease the rates of autism, suggesting that thiomersal could not be the primary cause of autism. A study on children from Demark, Sweden and California likewise argued against TCVs being causally associated with autism.
Scientific consensus
Due to growing concerns in the public, in 2001 the Centers for Disease Control and the National Institutes of Health asked the U.S. National Academy of Science's (NAS) Institute of Medicine to establish an independent expert committee to review hypotheses about existing and emerging immunization safety concerns. This initial report found that based on indirect and incomplete evidence available at the time, there was inadequate evidence to accept or reject a thiomersal-autism link, though it was biologically plausible.Since this report was released, several independent reviews have examined the body of published research for a possible thiomersal-autism link by examining the theoretical mechanisms of thiomersal causing harm and by reviewing the in vitro, animal, and population studies that have been published. These reviews determined that no significant evidence exists to establish thiomersal as the cause of autism or other neurodevelopmental disorders.
The scientific consensus on the subject is reflected in a follow up report that was subsequently published in 2004 by the Institute of Medicine, which took into account new data that had been published since the 2001 report. The committee noted, in response to those who cite in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
or animal models as evidence for the link between autism and thiomersal:
"However, the experiments showing effects of thimerosal on biochemical pathways in cell culture systems and showing abnormalities in the immune system or metal metabolism in people with autism are provocative; the autism research community should consider the appropriate composition of the autism research portfolio with some of these new findings in mind. However, these experiments do not provide evidence of a relationship between vaccines or thimerosal and autism.
In the absence of experimental or human evidence that vaccination (either the MMR vaccine or the preservative thimerosal) affects 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 concludes:
"Thus, based on this body of evidence, the committee concludes that the evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism." [bold in original]
Further evidence of the scientific consensus includes the rejection of a causal link between thiomersal and autism by multiple national and international scientific and medical bodies including the American Medical Association
American Medical Association
The American Medical Association , founded in 1847 and incorporated in 1897, is the largest association of medical doctors and medical students in the United States.-Scope and operations:...
, the American Academy of Pediatrics
American Academy of Pediatrics
The American Academy of Pediatrics is the major professional association of pediatricians in the United States. The AAP was founded in 1930 by 35 pediatricians to address pediatric healthcare standards. It currently has 60,000 members in primary care and sub-specialist areas...
, the American College of Medical Toxicology
American College of Medical Toxicology
The American College of Medical Toxicology , founded in 1993, is the largest organization of medical toxicologists in the United States and the world....
, the Canadian Paediatric Society
Canadian Paediatric Society
The Canadian Paediatric Society is a national association of paediatricians, committed to working together to advance the health of children and youth by nurturing excellence in health care, advocacy, education, research and support of its membership....
, the U.S. National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
, the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
, Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
, the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
, the Public Health Agency of Canada
Public Health Agency of Canada
The Public Health Agency of Canada is an agency of the Government of Canada that is responsible for public health, emergency preparedness, and response and infectious and chronic disease control and prevention...
, and the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
.
Consequences
The suggestion that thiomersal has contributed to autism and other neurodevelopmental disorders has had a number of effects. Public health officials believe fear driven by advocates of a thiomersal-autism link has caused parents to avoid vaccination or adopt "made up" vaccination schedules that expose their children to increased risk from preventable diseases such as measlesMeasles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
and pertussis
Pertussis
Pertussis, also known as whooping cough , is a highly contagious bacterial disease caused by Bordetella pertussis. Symptoms are initially mild, and then develop into severe coughing fits, which produce the namesake high-pitched "whoop" sound in infected babies and children when they inhale air...
. Advocates of a thiomersal-autism link have also helped enact laws in six states (California, Delaware, Illinois, Missouri, New York and Washington) between 2004 and 2006 to limit the use of thiomersal given to pregnant women and children, although later attempts in 2009 in twelve other states failed to pass. These laws can be temporarily suspended, but vaccine advocates doubt their utility given the lack of evidence for danger with thiomersal in vaccines. Vaccine advocates are also concerned that passage of such laws help fuel a backlash against vaccination and contribute to doubts about the safety of vaccines that are unwarranted.
During the period of time of removal of thiomersal, the CDC and AAP asked doctors to delay the birth dose of hepatitis B vaccine in children not at risk for hepatitis. This decision, though following the precautionary principle, nevertheless sparked confusion, controversy and some harm. Approximately 10% of hospitals suspended the use of hepatitis B vaccine for all newborns, and one child born to a Michigan mother infected with hepatitis B virus died of it. Similarly, a study found that the number of hospitals who failed to properly vaccinate infants of hepatitis B seropositive mothers rose by over 6 times. This is a potential negative outcome given the high probability that infants who acquire hepatitis B infection at birth will develop the infection in a chronic form and possibly liver cancer
Liver cancer
Liver tumors or hepatic tumors are tumors or growths on or in the liver . Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. These growths can be benign or malignant...
.
The notion that thiomersal causes autism has led some parents to have their children treated with costly and potentially dangerous therapies such as chelation therapy
Chelation therapy
Chelation therapy is the administration of chelating agents to remove heavy metals from the body. For the most common forms of heavy metal intoxication—those involving lead, arsenic or mercury—the standard of care in the United States dictates the use of dimercaptosuccinic acid...
, which is typically used to treat heavy metal poisoning
Heavy Metal Poisoning
Heavy Metal Poisoning is a song by American rock band Styx. It was included as the fifth track on their 1983 studio album Kilroy Was Here.The song in the story of Kilroy Was Here has the character of Dr Righteous preaching the evils of rock and roll...
, due to parental fears that autism is a form of "mercury poisoning". As many as 2 to 8% of autistic children in the U.S., numbering as many as several thousand children per year, receive mercury-chelating agents. Although critics of using chelation therapy as an autism treatment point to a lack of any evidence to support its use, hundreds of doctors prescribe these medications despite possible side effects including nutritional deficiencies as well as damage to the liver and kidney. The popularity of this therapy caused a "public health imperative" that led the U.S. National Institute of Mental Health
National Institute of Mental Health
The National Institute of Mental Health is one of 27 institutes and centers that make up the National Institutes of Health...
(NIMH) to commission a study about chelation in autism by studying DMSA, a chelating agent used for lead poisoning, despite worries from critics that there would be no chance it would show positive results and it would be unlikely to convince parents to not use the therapy. Ultimately, the study was halted due to ethical concerns that there would be too much risk to children with autism who did not have toxic levels of mercury or lead due to a new animal study showing possible cognitive and emotional problems associated with DMSA. A 5-year-old autistic boy died from cardiac arrest immediately after receiving chelation therapy treatment using EDTA in 2005.
The notion has also diverted attention and resources away from efforts to determine the causes of autism. The 2004 Institute of Medicine report committee recommended that while it supported "targeted research that focuses on better understanding the disease of autism, from a public health perspective the committee does not consider a significant investment in studies of the theoretical vaccine-autism connection to be useful at this time." Alison Singer, a senior executive of Autism Speaks
Autism Speaks
Autism Speaks is the world's largest autism advocacy organization that sponsors autism research and conducts awareness and outreach activities aimed at families, governments, and the public. It was founded in February 2005 by Bob Wright, vice chairman of General Electric, and by his wife Suzanne, a...
, resigned from the group in 2009 in a dispute over whether to fund more research on links between vaccination and autism, saying, "There isn't an unlimited pot of money, and every dollar spent looking where we know the answer isn't is one less dollar we have to spend where we might find new answers."
Court cases
From 1988 until August 2010, 5,632 claims relating to autism were made to Office of Special Masters of the U.S. Court of Federal Claims (commonly known as the "Vaccine Court") which oversees vaccine injury claims, of which one case has received compensation, 738 cases have been dismissed with no compensations made, and with the remaining cases pending. In the one case which received compensation, the U.S. government agreed to pay for injury to a child that had a pre-existing mitochondrial disorderMitochondrial disease
Mitochondrial diseases are a group of disorders caused by dysfunctional mitochondria, the organelles that are the "powerhouses" of the cell. Mitochondria are found in every cell of the human body except red blood cells...
who developed autism-like symptoms after multiple vaccinations, some of which included thiomersal. Citing the inability to rule out a role of these vaccinations in exacerbating her underlying mitochondrial disorder as the rationale for payment, CDC officials cautioned against generalizing this one case to all autism-related vaccine cases as most patients with autism do not have a mitochondrial disorder. In February 2009, this court also ruled on three autism-related cases, each exploring different mechanisms that plaintiffs proposed linked thiomersal-containing vaccines with autism. Three judges independently found no evidence that vaccines caused autism and denied the plaintiffs compensation. Since these same mechanisms formed the basis for the vast majority of remaining autism-related vaccine injury cases, the chance for compensation in any of these cases has significantly decreased. In March 2010, the court ruled in three other test cases that thiomersal-containing vaccines do not cause autism.