An Interpretive Dance
As the court dates draw closer, a flurry of studies both to disprove and support the thimerosal/autism link has been released. Typically they have been criticized by one side or the other as conducted by researchers with a bias or conflict of interest. And some rely on small sample sizes that can be easily dismissed. Which is why the latest flash point is over what could be a comprehensive source of data. Several HMOs are paid by the federal government to provide children's immunization and medical records for the CDC's Vaccine Safety Datalink, a database used to track pos-sible adverse side effects of vaccines. After the discovery that mercury levels had exceeded EPA guidelines, the CDC's Thomas Verstraeten reviewed medical records of 110,000 children. A confidential February 29, 2000, version of his report obtained through the Freedom of Information Act showed that the "relative risk" for autism in infants receiving 62.5 micrograms or more of mercury by the age of three months (as had most children abiding by the vaccine schedule) was 2.48 times higher than in infants who did not. In courts of law, a relative risk of 2.0 or higher has been considered sufficient proof that a given exposure causes disease. The figure was especially significant given that autism is typically not diagnosed until after age three, and 40 percent of the children in the study were younger.
Yet these findings were never published or even disclosed to CDC advisory-committee members. Prior to a meeting of the committee in June 2000 to discuss the report, CDC officials apparently added to the study's database children born with congenital disorders (who had previously been excluded) and two groups of babies not yet one year old. Such statistical adjustment reduced the relative risk for autism to 1.69, comfortably below the legal threshold for causation. The lower number was provided to the CDC's advisory-committee members.
Nevertheless, as a transcript of that meeting reveals, even the adjusted results—which still showed statistically significant relationships between thimerosal exposure and subsequent diagnoses of attention deficit disorder, language and speech delays, and a host of other neurodevelopmental problems—startled committee members.
When one member asked Verstraeten why risks of neurodevelopmental problems were higher in children with greater exposure to thimerosal, he replied, "Personally, I have three hypotheses: My first hypothesis is it is parental bias: The children that are more likely to be vaccinated are more likely to be picked up and diagnosed. Second hypothesis: I don't know—there is a bias that I have not recognized, and nobody has yet told me about it. Third hypothesis: It's true—it's thimerosal."
Asked by another member whether that third hypothesis was clearly biologically plausible, Verstraeten responded, "When I saw this, and I went back through the literature, I was actually stunned by what I saw, because I thought it was plausible."
Bill Weil, a pediatrician representing the AAP's environmental-health committee, noted, "There are just a host of neurodevelopmental data that would suggest that we've got a serious problem.… The number of kids getting help in special education is growing nationally and state by state at a rate we have not seen before."
"Forgive this personal comment," added Dr. Richard Johnston, a Colorado immunologist, "but I got called out for an emergency call and my daughter-in-law delivered a son by C-section. Our first male in the next generation, and I do not want that grandson to get a thimerosal-containing vaccine until we know better what is going on."
Verstraeten's results also worried committee member Robert Brent, a developmental biologist and pediatrician from Thomas Jefferson University. "The medical/legal find- ings in this study, causal or not, are horrendous, and therefore, it is important that the suggested epidemiological, pharmacokinetic, and animal studies be performed," Brent said. "If an allegation was made that a child's neurobehavioral findings were caused by thimerosal-containing vaccines, you could readily find a junk scientist who would support the claim with 'a reasonable degree of certainty.' But you will not find a scientist with any integrity who would say the reverse with the data that is available…. So we are in a bad position from the standpoint of defending any lawsuits if they were initiated, and I am concerned."
Perhaps because of such concerns, the committee decided to go along with the CDC's view that it should refrain from stating a preference for thimerosal-free vaccines. The fear was that such a statement would discourage physicians and clinics from using existing inventories, and immunization rates might fall if thimerosal-free versions weren't available everywhere. But the financial impact to manufacturers was mentioned three times by the CDC's Roger Bernier. "It could entail financial losses of inventory if current vaccine inventory is wasted," he said. "It could harm one or more manufacturers and may then decrease the number of suppliers."
Transcripts also reveal that some members of the committee went on to discuss various ways to "push" and "pull" the data further. Weldon and other critics allege that's just what happened. When the final version of the study was published in the November 2003 Pediatrics, Verstraeten—who'd since left the CDC to work for vaccine maker GlaxoSmithKline—claimed he had found "no consistent significant associations between TCVs and neurodevelopmental outcomes."
Writing to the CDC director, Rep. Weldon says that given the appearance of data ma-nipulation and conflict of interest, the CDC should open up its entire vaccine database to independent scientists. He notes that geneticist Dr. Mark Geier paid the CDC for data sets, only to be given many with no usable data—treatment Weldon characterizes as "abysmal and embarrassing." Overall, he later wrote, "I have lost confidence in the ability of the CDC officials to give an honest evaluation of the matters at hand."
Thanks to Weldon's intervention, Geier has now been able to use the CDC database to compare autism rates among more than 85,000 children who received a TCV for diphtheria/tetanus/acellular pertussis (DTaP) with rates among nearly 70,000 children who got the thimerosal-free version. In the TCV group, the risk of autism was 27 times higher. Geier's analysis is before two journals. Meanwhile, Dr. Walter Spitzer, a highly respected epidemiologist, has reviewed it and says, "This is important and needs to get out immediately. I see no major flaws. It is sound epidemiologically."
"Denying the existence of the tragic, massive autism epidemic will neither cure the problem nor restore confidence in our much-needed vaccine program," says Geier. "Rather, we must admit our past mistakes openly and honestly and then work to improve current and future vaccines. The first step is the removal of thimerosal from all vaccines, which we predict will result in the end of the autism epidemic."
And that's the true test of the thimerosal theory: Will rates of autism and related disorders decline in the years ahead? In May 2003 the AAP stated, "All routinely recommended infant vaccines currently sold in the U.S. are free of thimerosal as a preservative and have been for more than two years." Yet because the FDA maintained it did not have the scientific evidence to justify a recall of thimerosal, vials distributed prior to the introduction of thimerosal-free versions were allowed to remain on the market until they became outdated. That means that regularly mandated TCVS were still available until November 2002. And injections of Rho D containing 10.5 micrograms of mercury per dose were on the shelves until April 2003, even though Rho D was produced in single-dose vials that don't require a preservative. "Because the FDA chose not to recall thimerosal-containing vaccines in 1999," the House Committee on Government Reform April 2003 report concludes, "in addition to all of those already injured, 8,000 children a day continued to be placed at risk for overdose for at least an additional two years."
This timetable is crucial to the coming legal battle. If federal health officials had ordered the removal of thimerosal by a specific date, there would be a clear line in the sand to definitively indicate whether exposure promoted neurological damage. As it is, the beginning of a trend may be detectable in 2004, but due to the typical age of diagnosis, a full assessment won't be possible until late 2008 or early 2009.
Meanwhile, though, the federal vaccine injury court is seeking to determine whether sufficient evidence exists that thimerosal caused harm to the children in the 3,500 cases before it. The court was created in 1988 to prevent drug companies from abandoning manufacturing vaccines due to rising liability costs. Before suing manufacturers, families must file claims through the federal Vaccine Injury Compensation Program, which awards damages from a fund financed by a fee tacked on to each vaccine's price. A team of special masters hears claims; the federal government is represented by the Justice Department. Regardless of the outcome, families can then move to civil court. In November 2002, the Justice Department asked the vaccine court to seal all documents in the autism cases; only days earlier, congressional Republicans had sneaked a provision into the homeland security bill that would shield Eli Lilly and other pharmaceutical companies from civil suits over thimerosal. Both moves were thwarted by public outcry from parents' groups. Still, because government agencies and industry have been recalcitrant about handing over documents, the discovery process has stalled and families are starting to be allowed to move to civil court.
If the thimerosal theory starts to gain traction in court, the cost to the $8 billion-a-year industry could be gigantic. Approximately 40 million American children were immunized in the 1990s. If current rates hold true, roughly 160,000 will be diagnosed with classic autism, another 270,000 with autistic spectrum disorders, and as many as 2 million with pervasive developmental disorders.
But whether or not thimerosal is found to be instrumental in the problems facing any of these children, the systemic flaws that allowed mercury levels in vaccines to exceed federal guidelines must be fixed. In a move observers consider highly significant, former AAP official Neal Halsey also wrote a letter to Pediatrics criticizing Verstraeten's study. In it, he suggests that an independent scientific body should review the data and take charge of evaluating vaccine safety. Having the CDC recommending vaccines and assessing their safety, Halsey has said, "is a problem."
And while the immunization program is laudable, zeal for full compliance sometimes backfires. In an email sent to AAP officials back in 1999, Ruth Etzel of the Department of Agriculture made that point eloquently: "As you know, the Public Health Service informed us yesterday that they were planning to conduct business as usual and would probably indicate no preference for either product. While the Public Health Service may think that their 'product' is immunizations, I think their 'product' is their recommendations. If the public loses faith in the PHS recommendations, then the immunization battle will falter. To keep faith, we must be open and honest now and move forward quickly to replace these products."
The jury is still out as to whether thimero-sal injections caused the autism epidemic or whether the concern over ethylmercury will expose methylmercury or another compound to be the true culprit. But what is certain—as evidenced by a 10-year interagency push to study all possible causes of autism announced last November—is that researchers and policymakers are no longer dismissive of environmental factors. "To cling to a purely genetic explanation for autism is a desperate attempt to maintain the illusion that one lives in a comfortable and rational world where new chemicals and technologies always mean progress; experts are always objective and thorough; corporations are honest; and authorities can be trusted," says Harvard's Martha Herbert. "That human actions, rather than genes, might be responsible for compromising the health of a significant proportion of a whole generation is so painful as to be, for many, unthinkable."
Soon, however, jurors will be joining the ranks of those who've been forced to give the matter some very serious thought.