Thimerosal and MMR revisited: a troublesome tale

April 2004

On page 2 of the print edition of this issue of Infectious Disease News is an article by Bryan Bechtel describing the retraction of “an interpretation” by 10 of the 13 authors of a paper that was published in The Lancet in 1998. This paper proposed a possible link between measles-mumps-rubella (MMR) vaccine and autism in children and has become a rallying point for that segment of the public, primarily in the United Kingdom, that is opposed to immunization. In these comments, I would like to expand on the information in the article and broaden the focus to the belief on the part of some in the United States that thimerosal, not MMR, was really the villain in the autism saga. Although not a primary concern of adult infectious disease physicians, it is an instructive saga of flawed science, politics, greed and public policy gone terribly awry.

Original article

The original Lancet article (Wakefield AJ, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998;351:637-641) described 12 consecutive children with a history of pervasive developmental disorder and gastrointestinal symptoms, including abdominal pain, diarrhea, bloating and in some, food intolerance. These children were then subjected to an extensive medical work-up, which revealed gastrointestinal abnormalities, such as lymphoid nodular hyperplasia and/or ulceration.

Onset of symptoms was associated temporally with receipt of MMR vaccine in eight of the 12 children and with measles infection in another child. In their discussion, the researchers raised the possibility that MMR vaccine did in fact cause the gastrointestinal symptoms and developmental disorders, also citing some similar associations made in the past.

Such was the nature of the evidence supporting the MMR causation hypothesis for autism. As noted in the accompanying article, however, this report quickly became the rallying point for anti-vaccine lobbyists, and MMR vaccination rates plummeted. The damage in the United Kingdom had been done.

Meanwhile, in the United States, the concerns shifted to thimerosal. As noted in a Wall Street Journal editorial on Dec. 29, 2003, “The Politics of Autism,” this is a story of “politics and lawyers trumping science and medicine.” Thimerosal, ethyl mercury, is well-known as a potent microbicide and has been used for decades as a preservative in multidose vials of many killed vaccines in a concentration of no greater than 0.01%. It has never been linked or even suspected of being a heath hazard when used in that fashion.

A related but not identical compound, however, methyl mercury, became recognized as a widespread environmental toxic pollutant. This compound is a known human health hazard, the principal target organ being the central nervous system. Three separate agencies of the federal government have developed minimum allowable doses of methyl mercury ingestion, and they differ by as much as four- to fivefold. All of them, however, are based on the lowest observed levels at which symptoms begin to appear in experimental animals, and then divided by a “safety factor” of 10. No such standards exist for ethyl mercury.

A precipitous decision?

Concerns began to be expressed because of the expanded pediatric immunization schedule and the recognition that the total ethyl mercury exposure in vaccines in the first 6 months of life began to approach or even exceed the recommended limits of methyl mercury exposure. Even though ethyl mercury is a different compound, and is eliminated from the body seven times faster than methyl mercury, a decision was made, rather precipitously and with little scientific debate, to eliminate the use of ethyl mercury as a preservative in vaccines.

The explanation to the public that this was being done simply as a safety measure was not reassuring and led to further skepticism that the government and the vaccine manufacturers knew more than they were telling the public about the damage being done by mercury in vaccines. Not surprisingly, it was easy for the vaccine critics to make the short leap from concern about mercury to “thimerosal causes autism.” Fortunately, this issue hasn’t had nearly the public health impact in the United States that the Wakefield article had in Great Britain. However, the persistence of vaccine “skeptics” in Congress, as exemplified by Rep. Dan Burton of Indiana, whose family has had its own terrible experience with autism, has ensured that the vaccine safety issue will not go away. Plaintiffs’ lawyers continue to earn substantial incomes taking vaccine manufacturers to court claiming vaccine injuries, no matter how preposterous the claim.

Not just an issue of science

The retraction of the interpretation that MMR vaccine may have caused the developmental disorders described in the Wakefield report was published as a brief note in the March 6, 2004, Lancet, page 750. Only 12 of the 13 authors could be contacted. Ten retracted their interpretation, and two authors, including Dr. Andrew Wakefield, persisted in their interpretation.

The reasons cited for the retraction were of interest, for they noted that “the possibility of such a link was raised and consequent events have had major implications for public health. In view of this, we consider now is the appropriate time that we should together formally retract the interpretation placed upon these findings in the paper.” No mention was made of the several allegations that have been raised involving conflicts of interest and undisclosed sources of funding.

The Lancet’s editors, however, noted that certain facts were not disclosed, including the fact that the lead researcher, Dr. Wakefield, was carrying out an evaluation to determine if there was enough evidence to support a legal action against MMR manufacturers claiming the vaccine had damaged their children. Enough allegations have been raised, however, that an official investigation is being planned. It would appear there is at least reason to question whether the lead investigator was free of bias. How these recent events related to the Wakefield paper will play out in the United Kingdom remains to be seen.

Space does not permit a recounting of the many good epidemiological studies published in the last decade that have failed to find any evidence of linkage between MMR and autism and between thimerosal and autism. (Lest there be any confusion, thimerosal was used as a preservative only in killed vaccines; MMR, being a live-virus vaccine, contained no thimerosal or other preservative.)

Although it is logically impossible to prove a universal negative, there is certainly by this time an abundance of epidemiologic evidence that has not found credible evidence of such a link.

More is sure to follow on this troubling issue of vaccine safety and public distrust.