June 9, 2004 -- For the past two decades, a fierce battle has been raging over whether childhood vaccines can cause autism. On May 18, many thought the battle was finally over, laid to rest by a report released by the Institute of Medicine (IOM) Immunization Safety Review Committee.
In the report, the committee says that scientific evidence -- based on a significant number of studies conducted since 2001-- supports no association between autism and either measles-mumps-rubella (MMR) vaccines or those containing thimerosal, a mercury-based preservative.
"We believe that these conclusions were rendered prematurely," Mady Hornig, MD, lead researcher of a new study of thimerosal, tells WebMD. She is an associate professor of epidemiology and director of translational research at the Jerome L. and Dawn Greene Infectious Disease Laboratory, Mailman School of Public Health, at Columbia University in New York.
Brain Damage Seen in Mice
Her study showed that giving thimerosal to susceptible mice caused behaviors and brain changes similar to those found in autism. This study was one of several reviewed by the IOM committee before they drafted their statement on vaccine safety.
The study is published in the July issue of Molecular Psychiatry.
"This type of study, while certainly interesting, in no way substitutes for actual human evidence," IOM panelist Steven Goodman, MD, PhD, MHS, associate professor of oncology and epidemiology at the Johns Hopkins School of Medicine in Baltimore, tells WebMD.
"We don't have an animal model for autism and we don't understand exactly what causes autism. ... So we don't understand it completely in either system at the moment, and we certainly don't understand to what extent one is a model for the other."
Although autism was once considered a rare condition, the number of children diagnosed with autism has increased tenfold since 1985, to about one in every 1,000 children. Whether this is an actual increase in the disease or just an increase in the diagnosis of the condition is not clear.
About one third of children with autism have increased risk of autoimmune diseases, suggesting that genetics may play a role in autism. To examine the relationship between genetics and environment, researchers in the mouse experiment gave thimerosal to a genetic strain of mice susceptible to autoimmune diseases.
The exposed mice had a limited range of behaviors, reacted strangely to new environments, were less likely to explore, and appeared anxious. Their brains were larger, and there were structural changes in the same brain areas involved in human autism.
Hornig says her findings show that the same genes involved in predicting mercury-related and immune system damage also predict [brain] damage. Her findings, she says, show an association with the development of features reminiscent of autism.
Although the IOM panel considered results from Hornig's experiment when they drafted its report, the panel put greater weight on large public health studies in humans, panel chairwoman Marie C. McCormick MD, ScD, tells WebMD.
An Unlikely Link?
The IOM panel acknowledged that mercury can damage nerves and the brain and that autism is a devastating disorder meriting additional research into its causes and treatments. However, they concluded that pursuing the link between the two is unlikely to be productive, in part because theories of how the MMR vaccine and thimerosal could trigger autism lack supporting evidence.
"We didn't say that investigations shouldn't continue in the lab on the effects of mercury, on the effects of thimerosal, and on the causes and profiles of autism," Goodman says. "Where the committee thought that research dollars probably shouldn't go, at least for the moment, are these large-scale [public health] studies linking autism and thimerosal exposure."
But Hornig counters that the reviewed studies may have been of poor quality, inadequately estimating the risk associated with these preservatives. She says they failed to account for genetics, age, sex, nutrition, dosing schedule, and other factors known to affect how mercury interacts with the body.
"The pronouncement that research funds are better applied elsewhere effectively forecloses any possibility of federal funding for an entire field of research," she says. "The timing is particularly unfortunate given that we are only just beginning to define the mechanisms by which environmental factors such as thimerosal interact with immune response genes during early development."
McCormick says the IOM committee recommended that "available funding for autism research be channeled to the most promising areas, of which the link with vaccines does not appear to be one."
However, the committee did recommend keeping track of new cases of autism, which would be expected to decrease along with declining use of thimerosal-containing vaccines if indeed mercury increases the risk of autism.
"The IOM crossed a line when they went so far as to say that there should be no new research on the link between vaccines and autism," Barbara Loe Fisher tells WebMD. She is president and founder of the National Vaccine Information Center (NVIC), a nonprofit organization dedicated to the prevention of vaccine injuries and deaths through public education.
"In science and in medicine, there are many instances where what is true today may not be true tomorrow. This report tried to close the door, and I thought it went too far."
Compared with earlier IOM reports in 1991, 1994, and 2001, which said that evidence was not sufficient to accept or reject a link between vaccines and autism, Fisher says the present report uses stronger language and "too much reliance on [public health] studies, basically just looking at old medical records, and not on basic sciences."
Since 2001, five large public health studies conducted in the U.S., the U.K., Denmark, and Sweden showed evidence that there is no association between thimerosal-containing vaccines and autism.
The use of thimerosal in vaccines has declined since manufacturers began removing it from childhood vaccines in 1999. Since 2001, all universally recommended childhood vaccines are available in single-dose vials containing no thimerosal. Certain flu vaccines and tetanus-diphtheria vaccines, however, given to children age 7 and older contain thimerosal as a preservative. The MMR vaccine has never contained thimerosal.
"It was clear from the report that we were not giving thimerosal a clean bill of health," Goodman says.
"We didn't say that thimerosal is something that we should want in vaccines; we said that the safest vaccines are indeed thimerosal-free vaccines. We only said that the evidence favored that there was not a connection between autism and thimerosal exposure."
An additional concern regarding mercury exposure from thimerosal is how it might add together with other mercury exposures, such as eating seafood. Hornig says that ethylmercury, the form found in thimerosal, causes more damage to the developing brain than does methylmercury, the form that is found in fish.
"We live in a world where there is exposure to mercury from multiple sources, and some of it may be unavoidable," Goodman says. "To the extent that there is mercury in the air, we can't stop breathing. To the extent that there is mercury in certain foods, obviously we can avoid fish, but anything else we may not know about."
The IOM panel recommended further studies of the amount of mercury exposure from thimerosal and other forms of mercury in infants, children, and pregnant women.
"Thimerosal was removed from vaccines as a precautionary measure to reduce the exposure to mercury from all sources," McCormick says. "There is no evidence that the amount of mercury present in vaccines resulted in health problems."
The IOM committee emphasized that children should still receive the full course of recommended vaccinations to prevent infectious diseases and that they should get thimerosal-free vaccines to minimize overall mercury exposure. These recommendations are consistent with those of the American Academy of Pediatrics and the U.S. Public Health Service, who in July 1999 issued a joint statement calling for the removal of thimerosal from vaccines.
Thimerosal Still Around?
On May 20, the Office of Special Counsel, an independent investigative and prosecutorial agency handling "whistleblower" complaints, forwarded to congressional oversight committees hundreds of disclosures alleging public health and safety concerns regarding the possible link between thimerosal-containing vaccines and autism, many from parents of children with autism or other neurological disorders.
Contrary to statements from Department of Health and Human Services agencies, the HHS Office of Investigations, and the American Academy of Pediatrics, the disclosures claim that some childhood vaccines with expiration dates of 2005 contain 25 micrograms of mercury and continue to be produced and administered.
As a next step, the IOM panel recommends developing programs to increase public participation in vaccine safety research and policy decisions and to promote constructive dialogue between scientists, government officials, and the public about research findings and their implications for policy development. For the past two decades, the NVIC has been mandating independent, non-governmental, non-industry research into the genetic and other biological high risk factors of vaccine-associated brain and immune system dysfunction, including autism.
"There needs to be more transparency, access to the data by more researchers, and a greater collaborative effort by the government or there will be a loss of trust," Fisher says. "I am cautiously hopeful that they will do this."