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Toxic Tipping Point

Are the CDC, the FDA, and other health agencies covering up evidence that a mercury preservative in children's vaccines caused a rise in autism?

Between the Cracks

Anyone who recalls the stinging sensation of having a skinned knee painted with a reddish-orange antiseptic called Merthiolate has an intimate acquaintance with thimerosal, simply another name for the bacteria-killing compound developed by Eli Lilly in 1929. Early internal safety data on injections containing thimerosal were not encouraging. In 1935, for example, a researcher reported to Lilly that adverse reactions indicated that thimerosal was "unsatisfactory as a preservative for serum intended for use on dogs."

Yet that same year, thimerosal began to be added to childhood vaccines. Mostly it was used in large, multidose vials in which contamination can arise from repeated needle re-entry. Individually bottled vaccines don't require preservatives but are more expensive, and a mercury-free preservative has been used by one pediatric vaccine maker since 1997; but in 1999 most infant vaccines used in the United States contained thimero-sal (as, indeed, some flu and booster shots—and most infant vaccines used in the developing world—still do).

Back in 1935, the FDA didn't yet regulate drugs and vaccines. But even once it did, remarkably, thimerosal was never required to undergo clinical testing. When FDA officials asked Lilly for safety data in 1973, shortly before reviewing thimerosal's use in over-the-counter products, Lilly's director of regulatory affairs responded, "[I]t would be difficult to get recognized researchers to conduct new studies for safety or efficacy. They believe that over 40 years of wide usage has proven efficacy and safety beyond that which could be done in special studies." Nine years later, FDA officials recommended pulling over-the-counter products containing thimero-sal from the market, though 16 years passed before they were. And, still, its use in vaccines went unexamined. Thimerosal also continued to bypass toxicity testing, even after federal regulations for reviewing vaccines required it. "The absence of appropriate preclinical testing of thimerosal is a staggering oversight," FDA drug reviewer Dr. Eric Colman wrote in 2002, after his son was diagnosed with an autistic spectrum disorder.

The Tipping Point?

When autism was first recognized as a neurological disorder in 1954, the symptoms described were essentially the same as those currently used for diagnosis of classic autism: severely limited speech, impaired social interaction, and repetitive behaviors such as arm flapping. Today, the broader autistic spectrum includes less severe forms in which some children may speak but have unusual behaviors and learning disabilities, or have high IQs but difficulty with social interaction, a common characteristic of Asperger's syndrome.

Psychologist Bruno Bettelheim once convinced doctors that autism was attributable to the bad parenting of "refrigerator moms." After that theory was scrapped, autism was assumed to be an unavoidable genetic fate. But the exponential rate increases have led more and more scientists to suspect that autism might result from an interplay between genetic vulnerability and nongenetic causes, says Harvard pediatric neuroscientist Dr. Martha Herbert. "This new line of investigation calls for a knowledge of toxicology, genetic individuality, and biochemistry much more detailed than most current autism researchers possess."

Those who believe in the thimerosal/autism theory suggest that the precise form the disease takes simply reflects the degree of mercury exposure. Vaccines are just one pathway for mercury to reach and accumulate in the fetal or infant brain, but a high exposure at a key time might—especially for children genetically ill- disposed to flush the toxin—be the tipping point. For infants born to women with high mercury consumption, AAP vaccine-policy expert Neal Halsey commented back in 1999, "no one knows what dose of mercury, if any, from vaccines is safe.… We can say there is no evidence of harm, but the truth is no one has looked."

After the AAP announcement, a group of parents founded Sensible Action for Ending Mercury-Induced Neurological Disorders, or Safe Minds. Many members of Safe Minds (and other groups) are doctors, nurses, and researchers who stress that they are "anti-mercury, not anti-vaccine," says board member Mark Blaxill. "Virtually every step forward of any consequence with respect to the scientific agenda has come from parents. This is a new phenomenon: direct scientific activism by parents using their own professional skills to aggressively take on anyone who makes arguments based on sloppy science to try to make this problem go away."

In 2001, two Safe Minds board members, Lyn Redwood, a nurse, and Sallie Bernard, a market researcher, published a study in the journal Medical Hypotheses that detailed overlaps between symptoms of autism and those of mercury toxicity. They noted, for example, that a brand of teething powder containing mercury was popular until the 1950s, when a doctor finally connected it to Pink's disease, which had symptoms similar to autism. Once the teething powder was removed from the market, Pink's disease disappeared.

Blaxill himself published a paper in the April 2003 Journal of Autism and Developmental Disorders that outlined errors made in a study by public-health experts who argued that the rise in autism rates could be partly accounted for by diagnostic substitution, i.e., children previously categorized as mentally retarded now diagnosed as autistic. Blaxill's analysis prompted the study's authors to concede that his criticisms were valid. A partner in a leading business-strategy firm, Blaxill says that he "learned to be skeptical of 'experts'" in his business. "I'm not intimidated by numbers or science," he says. "I know how people can lie with numbers, and if there's one thing I'm good at doing, it's taking those numbers apart to find the truth. The CDC has been lying with numbers regularly."

Blaxill also contributed to a study led by Louisiana physician Amy Holmes, who is the mother of an autistic child, which analyzed mercury levels in samples collected from baby hair. The August 2003 International Journal of Toxicology study revealed that healthy children excreted eight times more mercury via their hair than did autistic children. In fact, the more severe a child's autistic symptoms, the less mercury was excreted in her hair, indicating that mercury also could be retained in the child's tissue, including her brain.

Because mercury crosses the placental barrier, the study also examined maternal exposure to mercury via food, dental fillings, and the thimerosal-containing Rho D immunoglobulin injections typically given to Rh-negative women—16 percent of the population—during pregnancy. Prior to the mid-1980s, an Rh-negative woman was given this injection only after delivery to prevent complications that can occur if the baby is Rh-positive. But Rh-negative women now receive Rho D injections at 28 or 34 weeks, and any time there is a chance of a mother's blood mixing with the baby's—after undergoing amniocentesis, for instance. The study found that nearly half of the autistic children's mothers had received Rho D injections, compared with only 9 percent in the control group. In addition, 37 percent of mothers in the autistic group also had 10 or more fillings containing mercury, compared with only 18 percent in the control group. The authors suggest that the near absence of mercury in hair samples of autistic infants despite higher exposure indicates that TCVs could be the last straw for children whose ability to excrete mercury is impaired or who are near a dangerous threshold due to maternal exposure.

But it's not just parents who are conducting important research about thimerosal. Boyd Haley, a University of Kentucky biochemist who researches heavy-metal neurotoxicology, explains that APO-E—a protein crucial in carrying mercury out of the body—comes in three varieties, ranging from one that can carry out two atoms of mercury for every molecule of APO-E, to the least protective version, APO-E4, which doesn't carry out any. Both autistics and Alzheimer's patients tend to have APO-E4. "There is clearly a subpopulation of people who can't excrete even low levels of mercury effectively," says Haley. He also found evidence that may explain why for every autistic girl, there are four autistic boys. When he added estrogen to a petri dish of thimerosal and brain cells, the hormone reduced the rate of brain cells killed by thimerosal, whereas adding testosterone dramatically increased the death rate. Based on his results, Haley says no level of mercury can be considered a "safe dose" for infants.

Haley—whose thimerosal research was tangential to what he's best known for, developing successful diagnostic tests for Alzheimer's—says that once he published the risks of mercury in vaccines and dental fillings, he found himself turned down for NIH grants, after being consistently funded for decades. "People told me I would have funding problems if I worked on mercury, and they were right," Haley says.

Richard Deth, a Northeastern University pharmacologist, has found that even low levels of thimerosal affect a critical neural pathway regulating brain-cell growth. When Deth submitted his study to Proceedings of the National Academy of Sciences, he said he was rejected on the grounds that it hadn't met standards for "exceptional importance and novelty." Deth was dumbfounded: "I keep hearing from public-health officials that there is no scientific basis to support a connection between thimerosal exposure and autism. Yet here I am bringing it to you and it's not considered important?"

"We are treated all too often," says a researcher who insists that anonymity equals continued funding, "to patronizing remarks by researchers about 'hysterical parents' who 'can't accept their child's genetic fate'; highly publicized but methodologically weak and conflict-of-interest-ridden studies that claim to definitely refute any role for various vaccines in the increased rates of autism but raise no alarms about the increased rates themselves; and a press blackout on subsequent critiques and refutations."

Rep. Weldon has heard similar complaints from other researchers and is examining whether the NIH peer-review system has become as politicized as they contend. "I've heard that if you start wading into this," he says, "you can ruin your career."

Protect the Herd

Why would there be a backlash against researchers who investigate the interplay between TCVs and autism? Aside from liability issues and conflicts of interest (more on that later), the medical establishment is deeply protective of the national vaccine program, and "herd immunity"—ensuring that the highest number of people are vaccinated—is key to preventing diseases such as polio and rubella, which the program has been so successful in stamping out. And the anti-thimerosal lobby tends to get lumped in with the anti-vaccine movement, which threatens the herd.

In March 2003, a Pediatrics paper by Dr. Karin B. Nelson, a neurological researcher at NIH, and Dr. Margaret Bauman, a Harvard neuropathologist, challenged the thimero-sal/autism link first publicized by Safe Minds' Bernard and Redwood. They pointed out that there is no clear evidence that the ethylmercury in thimerosal has the same ability as the methylmercury found in fish to cross from the blood to the brain. (NIH researchers now studying thimerosal say it does but is flushed from the body much quicker and thus might not be as cumulatively toxic.) The Pediatrics paper also questioned whether autism increases are indeed real: "There has clearly been a broadening of the criteria for autism, better case-finding, increased awareness by clinicians and by families, and an increase in referrals…. Whether the sum of these is sufficient to account for the more frequent diagnosis of autism is a matter of contention and is properly settled by careful research."

But careful epidemiological research is being done by the state of California, where classic autism diagnoses nearly doubled between 1998 and 2002, and are 6.3 times higher than in 1987. The state commissioned a study to see if the increases could be explained by factors suggested in Pediatrics. Investigators, led by University of California-Davis epidemiologist Dr. Robert S. Byrd, verified all diagnoses and ruled out all alternative explanations except for better case finding and increased public awareness, which they didn't study. "That could be a contributing factor," says Byrd, "but for hyperawareness to explain the increases we've seen, we would have had to be missing 2 out of 3 cases of autism, so I don't think that's a plausible explanation....The increase we are seeing is real and unexplained."

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