Vaccines and Autism, Beyond the Fear Factors
By Jane E. Brody

Over the years, any number of coincidental findings have suggested that exposure to a particular substance may cause a certain illness. But under the critical eye of careful research, most of these apparent associations turn out to have no cause-and-effect relationship.

The suspicion that vaccines given to infants and children can cause autism is one such association, with attention directed at the vaccines that use the preservative thimerosal, which contains mercury.

Experts have poked many holes in this theory, which arose because of two facts: that mercury is a known neurotoxin and that symptoms of autism typically appeared soon after children were given vaccines containing thimerosal.

While the final "i" has yet to be dotted on this question, overwhelming evidence so far suggests that thimerosal poses no significant threat to the developing brain.

Erring on the side of caution three years ago, vaccine makers stopped using thimerosal to prevent microbial contamination of certain vaccines given to infants and small children, although none of the existing batches were recalled and remained in use until supplies ran out. Also, thimerosal is still used in flu vaccine, which is now recommended for otherwise healthy children ages 6 months to 2 years.

Keeping Open Minds
It is easy for parents to become convinced that thimerosal is the culprit in the current rise in autism rates if they consider only the arguments presented by those who believe in this association.

So it is important to review the evidence that experts have marshaled against it, which is described in the current issue of the journal Pediatrics by two neuropathologists, Dr. Karin B. Nelson of the National Institute of Neurological Disorders and Stroke and Dr. Margaret L. Bauman of Harvard Medical School.

In October 2001, a 15-member expert panel of the Institute of Medicine, an arm of the National Academy of Sciences, concluded that there was not enough evidence to prove or disprove a link between thimerosal and autism.

Meanwhile, Dr. Marie C. McCormick, the Harvard professor of maternal and child health who led the panel, suggested that parents ask their doctors to use mercury-free vaccines. But, she said, even if they are not available, parents should still have their children vaccinated.

The diseases that vaccines prevent can cause severe illness, brain damage and even death, and these real risks are far greater than anything that may be imagined to result from the vaccines themselves.

To be sure, the numbers of reported cases of autism and its milder forms are alarming: an increase from about 1 child in 2,000 before 1970 to a prevalence today of 1 in 500, 1 in 250 and possibly even 1 in 150, according to various estimates.

What accounts for the change remains a mystery: some environmental agent may be acting on the brains of susceptible children, or the change may simply reflect better recognition and diagnosis.

Thimerosal has been used to protect vaccines since the 1930's. But the change in diagnosis rates of autism has coincided with an increased exposure of American infants to vaccines preserved with thimerosal, which have included Haemophilus influenzae (HiB), hepatitis B, diphtheria and tetanus. This preservative is also used in some immunoglobulins given to pregnant Rh-negative women and some over-the-counter eardrops and nasal sprays.

Claims vs. Facts

Typically, children who are found to be autistic appear normal for their first months or year, then they seem to lose natural developmental landmarks. Many parents of affected children have noted that this reversal occurs suddenly or gradually soon after the vaccinations received in the child's first 15 months. But Dr. Nelson and Dr. Bauman point out that "age of onset of symptoms can be highly misleading as an indicator that some environmental event has caused or precipitated a disorder."

For example, in two disorders known to be caused solely by a defect in a single gene, a period of normal development occurs before symptoms appear — about 18 months in Rett syndrome and 45 years in Huntington's chorea, the disease that killed the songwriter Woody Guthrie.

Those who have focused on mercury as a cause of autism list nearly 100 clinical signs that they say are shared by autism and mercury poisoning. But Dr. Nelson and Dr. Bauman say this list does not distinguish between "typical and characteristic manifestations" and those that are "rare, unusual and highly atypical."

For example, the scientists said, in mercury poisoning, including the few cases of poisoning caused by ethyl mercury, the form in thimerosal, characteristic motor symptoms are lack of coordination, unsteadiness and difficulty speaking because of poor muscle control, along with tremors, muscle pains and weakness and, in severe cases, spasticity. But in autism, they said, the only common motor symptoms are "repetitive behaviors such as flapping, circling or rocking."

As for sensory symptoms, mercury poisoning is associated with extreme sensitivity to touch, a function of peripheral nerve damage. But in autism a reduced sensitivity to pain accompanies a hypersensitivity to sound, suggesting involvement of the central nervous system, not peripheral nerves.

There is even debate over ethyl mercury and whether it gets into the brain. Methyl mercury has an "active transport system" to carry it across the blood-brain barrier, but there is no such transport for ethyl mercury, which is further hindered from entering the brain by being a larger molecule that is rapidly decomposed once in the body.

Also striking, the scientists report, are differences in the brains, including size and the kinds of cells and areas that are damaged in autism and mercury poisoning. Children with mercury poisoning experience a shrinkage of the brain; those with autism tend to have abnormally large brains, with an enlarged cortex and white matter and more nerve processes than normal.

In an interview, Dr. Nelson suggested that the normal "pruning process" — the loss of extraneous neurons and connections that occur as children mature and gain experience — fails to happen in autism, leading to an enlarged brain. More studies should be done, she said, to reveal why autistic children seem unable to focus and are overwhelmed by environmental stimuli.

A further brain difference, she noted, lies in the brain cells: those that are relatively spared in mercury poisoning are damaged in autism, and vice versa.

Autism is known to have hereditary influences, and Dr. Nelson, among others, says that it "probably begins in the womb," the result of abnormal brain development. Although the symptoms usually do not become apparent until months or longer after birth, some mothers of autistic children have reported noticing abnormalities in their newborns before any mercury-containing vaccine was administered.

Through the years, several cases of serious mercury poisoning have occurred, including one involving a mercury-containing teething powder and another related to the contamination of fish consumed by millions of people in Japan. But still, no increase was seen in the incidence of autism or in behavior changes suggestive of autism.

Millions of children get vaccines every year, but fewer than 1 percent end up with autism. If vaccines are a factor, why would so many be spared? The hypothesis put forth by Sallie Bernard and colleagues at the parent organization Safe Minds in Cranford, N.J., is that some children are either born sensitive to mercury or fail to eliminate mercury normally and thus accumulate large amounts that can damage the brain.

Clearly, this matter deserves thorough scientific attention. Autism is a devastating condition that is very costly for child and family and, if cases can be prevented, they should be. If thimerosal is an important cause, the phasing out of its use in vaccines that is now occurring should result in a significant decline in cases in the next few years.