It wasn’t hard to predict that the London press would find the lone-wolf doctor narrative more appealing than the one told in reams of data. Typical of the ensuing coverage was a Guardian feature on Karen Prosser, the mother of a severely autistic child. “Prosser knew something was not quite right with her second baby, Ryan, when he was 15 months old,” the piece began. By the time Ryan was two, he’d lost the ability to speak. From the start, Prosser suspected her son’s developmental difficulties were related to his severe constipation. Her doctor, she said, told her she was being ridiculous.
Then Mrs Ryan [Prosser] saw an article about the work Dr Wakefield and colleagues had been doing at the Royal Free into possible links between the MMR vaccine and inflammatory bowel disease. . . .
“I can say I believe 100 percent it is the bowel that has caused his autism,” said Mrs Prosser. Ryan, four today, is a different child as long as he takes his medicines to keep the bowel disease at bay. He can now talk. The tantrums have stopped. He will look at people now and wants to be friends. Every day he learns new words.
Mrs Prosser believes the MMR vaccination set off the bowel disease which in turn caused Ryan’s autism. “Something caused the bowel to do this,” she said. “Bowels don’t just create inflammation. Something happened.”
Throughout that spring, the controversy raged on. In March, a group of thirty-seven leading health experts, ranging from pediatricians to psychiatrists, epidemiologists to gastroenterologists, and immunologists to virologists, was convened for a review of Wakefield’s paper. It, too, found his research lacking, his theories “biologically implausible,” and his conclusions essentially worthless. In the group’s final report, which was sent to every doctor in the country, it noted, “It would be surprising if the link had not been noted in other countries with good diagnostic facilities for autism where MMR has been widely given for many years.”
In the coming weeks, The Lancet’s correspondence pages would be filled with further indictments.28 Ten co-signers from the Institute of Child Health at University College London Medical School said they were “surprised and concerned that The Lancet published [a] paper . . . yet provided no sound scientific evidence”; three more from the Barnsley Health Authority’s Department of Public Health Medicine suggested it might be time for research publications to “to carry health warnings” so people can be “adequately appraised about the strength and quality of evidence presented.”
The substance of virtually all those letters was ignored by the media, which treated the evolving story as more of a horse race between competing claims: “Ban Three-in-One Jab, Urge Doctors After New Fears” and “Doctors Link Autism to MMR Vaccination” one day, “Research Rejects Autism Link with Vaccine” and “Triple Jab Is Safe, Says Medical Chief” the next. In those cases, at least, reporters and editors could claim the precise scientific arguments were over their, or their readers’, heads. The same could not be said about the contents of a letter that was sent to The Lancet by a doctor in the Wiltshire Health Authority’s Department of Public Health named Andrew Rouse. It arrived at The Lancet’s offices on March 4, just six days after Wakefield’s press conference. An edited version ran in the journal’s May 2 issue:
After reading Andrew Wakefield and colleagues’ article I did a simple Internet search and quickly found the Society for the Autistically Handicapped. I downloaded a 48-page fact sheet produced for the society by Dawbarns, a firm of solicitors in King’s Lynn.
It seems likely then that some of the children investigated by Wakefield et al came to attention because of the activities of this society; and information from parents referred in this way would suffer from recall bias. It is a pity that Wakefield et al do not identify the manner in which the 12 children investigated were referred (eg, from local general practitioners, self-referral via parents, or secondary/tertiary or international referral). Furthermore, if some children were referred, directly or indirectly, because of the activities of the Society for the Autistically Handicapped, Wakefield should have declared his cooperation with that organisation.
In the form that it appeared, Rouse’s letter was rather oblique. What was the Society for the Autistically Handicapped, and why did Rouse think it “likely” that the group had referred some of the children in Wakefield’s study? How was Dawbarns, the law firm at which Richard Barr worked, involved? The first public hints of the answer came from Wakefield himself, whose written response included a denial of “litigation bias” despite his having agreed to “evaluate a small number of these children on behalf of the Legal Aid Board.” An even fuller picture emerged on the Web address Rouse cited, which featured a copy of the Dawbarns pamphlet, which recommended to parents “who believed [their] child has been damaged” that they “seek proper compensation in the courts.” “We are working with Dr Andrew Wakefield of the Royal Free Hospital London,” it read. “He is investigating this condition. . . . If your child has developed persistent stomach problems (including pains, constipation or diarrhea) following the vaccination, ask us for a factsheet from Dr Wakefield.”
Still more pieces of the puzzle were available to anyone who did the type of “simple Internet search” Rouse had performed. For instance, an online search for “Dawbarns” and “Royal Free” would have turned up an article that had appeared fifteen months earlier: On November 27, 1996, The Independent ran a 1,300-word story about Rosemary Kessick, a forty-two-year-old former business manager whose son was one of more than three hundred children whom Dawbarns had assembled for its suit. The boy was also, according to the article, “one of 10 children taking part in a pilot study at the Royal Free Hospital in London, which is investigating possible links between the measles vaccine with the bowel disorder Crohn’s Disease, and with autism. The study is being organised by Norfolk solicitors Dawbarns, one of two firms awarded a contract by the Legal Aid Board in 1994 to co-ordinate claims resulting from the MMR vaccine.” It turned out that the parents of some of the children Wakefield had used to launch a worldwide vaccine scare were planning on suing the manufacturers of the MMR vaccine, that Wakefield’s lab had been paid £50,000 to collect data for the suit, and that the initial research proposal for the Wakefield-led, Dawbarns-funded study had stated its goal was to “establish the causal link between the administration of the vaccines and the conditions outlined.”29
None of this was reported at the time, nor was the public informed that nine months before his Lancet paper was published, Wakefield had filed a patent for “a new vaccine for elimination of MMR and measles virus and to a pharmaceutical or therapeutic composition for the treatment of IBD . . . and regressive behavioural disease.” Instead, London’s newspaper readers were treated to headlines such as “Measles Turned My Son into an Autistic Child” and “I Want Justice for My James—Study Boosts Mum’s Battle.” It would not be until years later that a freelance investigative reporter uncovered the truth behind Wakefield’s work—and by that point the damage had already been done.
24 The opioid excess theory was the brainchild of an Estonian-born psychologist named Jaak Panksepp, who, in the late 1970s, said he was struck by the behavioral similarities between morphine-addicted rats and autistic children, including “a lack of crying during infancy, a failure to cling to parents, and a generally low desire for social companionship.” Later in his career, Panksepp’s work on rodents led him to conclude that “boys born to mothers using opiates during the second trimester would be expected to have a higher incidence of homosexuality than the offspring of nonaddicted women.”
25 By the time the journal hit the stands, it looked as if Horton had been wondering the same thing. Only two years had passed since, at age thirty-three, he’d become the youngest editor in The Lancet’s 173-year history. During that time, he’d established a reputation for shaking things up; already, some of his professional peers were grumbling that his approach was more appropriate for buzzy, mass-market magazines than a staid research journal. In this instance, however, Horton tried to play it saf
e: The Lancet conspicuously declined to participate in the Royal Free press conference, a decision a spokesman said was made because it wanted to “avoid being alarmist,” but which some at the time interpreted as Horton’s desire to distance himself from a media maelstrom that he realized was inevitable. In his published commentary on the imbroglio, Horton simultaneously defended his decision to publish the paper and distanced himself from Wakefield’s publicity campaign: “Reported adverse comments about the safety of MMR vaccination were made at [the Royal Free’s] press conference,” he wrote. “By contrast, the views expressed in the paper are unambiguously clear: ‘we did not prove an association between measles, mumps, and rubella vaccine and the syndrome described.’ ”
26 There are several ways to conduct randomized trials. The ideal one is through a double blind test, in which neither the researcher nor the test subjects know who is being studied and who is a control. Double blind trials protect against the placebo effect on the part of the subject and observer bias (or wishful thinking) on the part of the researcher.
27 A real-world example of a theory proven to be true after all three types of studies were performed is the beneficial effects of fluoridation. First was the case series: A dentist noticed that patients with mottled teeth seemed to have less tooth decay. Next was the case control study: Children who’d spent their whole lives in an area with naturally fluoridated water were compared to those who’d moved there after their teeth had fully developed. Finally came the randomized clinical trial: A relatively homogeneous population was divided in two, with only one half receiving fluoridated water.
28 One of the few voices of support for Wakefield came from Barbara Loe Fisher, who wrote, “It is perhaps understandable that health officials are tempted to discredit innovative clinical research into the biological mechanism of vaccine-associated health problems when they have steadfastly refused to conduct this kind of basic science research themselves. . . . US public health officials will not accept any independent thinking or scientific investigation into vaccine-associated health problems that does not carry their imprimatur.”
29 In total, Wakefield received £435,643 for his involvement in the ultimately unsuccessful, publicly funded lawsuits filed by parents against the drug companies GlaxoSmithKline, Aventis Pasteur, and Merck.
CHAPTER 10
THIMEROSAL AND THE MYSTERY OF MINAMATA’S DANCING CATS
On the morning of January 28, 1928, just as he had most mornings for the previous two weeks, George Thomson began his day at the diphtheria vaccination clinic in Bundaberg, a small town on the Burnett River on the eastern coast of Australia. Thomson was Bundaberg’s general practitioner, and he doubled as the town’s chief public health official. Although diphtheria—a highly contagious respiratory infection that had long been one of the leading childhood killers in the region—had been in decline ever since the discovery of an effective antitoxin serum thirty years earlier, Thomson knew even a handful of cases carried the risk of a deadly outbreak. Hoping to forestall any potential epidemics, he’d implemented a voluntary vaccination program targeted at school-age children, who were among those at the greatest risk for the disease.
The program had begun smoothly enough. Using little more than a set of hypodermic needles and a large glass bottle of diphtheria vaccine, Thomson had vaccinated almost two dozen children in the first week alone. Twenty-one children showed up for their shots on the 28th, some for their first in the series and some for their second. With each patient Thomson performed the same routine: He swabbed the injection site with antiseptic, removed a syringe from a tray of saline solution, pierced the rubber top of his vaccine bottle with a needle, and administered the shot.
That day, however, something went horribly wrong. By early afternoon, eighteen of the twenty-one children Thomson had injected were convulsing, vomiting up “offensive green bile,” and showing other signs indicative of a sudden, aggressive infection. Less than two days later, twelve of those children were dead. An ensuing Royal Commission investigation discovered that Thomson’s bottle of vaccine, which he stored each night in a cupboard in his office, had at some point become contaminated with staphylococci bacteria. The children he’d injected on January 28 had contracted a particularly virulent form of staph infection, and the sickest had died of toxic shock. In an effort to protect his hometown, George Thomson had caused one of the most concentrated vaccine catastrophes on record.
As word of the Bundaberg tragedy spread, public health officials around the world began looking for ways to use sterilizing preservatives in multi-dose vials of vaccine. By the early 1930s they had settled on a recently synthesized ethylmercury compound called thimerosal. It seemed ideally suited to the role: It was inexpensive to manufacture, side-effect-free, and lethal to a broad range of microbes without undermining the potency of the vaccine it was mixed with.
Mercury’s unusual qualities—it is one of only six heavy metals that are liquid at or near room temperature—and its shimmering, silvery appearance have made it a source of fascination for millenia. In 210 B.C., Qin Shi Huang, the first ruler of unified China, died after consuming a mixture of mercury and jade he hoped would grant him eternal life. The ancient Romans, none the wiser, often used it as a cosmetic applied directly to their faces.
In the nineteenth century, a mercury compound called calomel was used to treat everything from tuberculosis and parasites to toothaches and constipation. By the 1950s, in addition to its role as a vaccine preservative, mercury was a common ingredient in any number of over-the-counter medicines. It has been used in amalgam dental fillings and topical antiseptics, and, for a period, was an ingredient in teething powders and de-wormers for small children. Even as its uses changed and multiplied, scientists had little codified knowledge of how mercury interacted with the human body. It wasn’t until 1956 that they had the chance to systematically assess its effects.
That spring, a five-year-old girl was admitted to a hospital in Minamata, the largest city on Kyushu, the southernmost of the four main islands of Japan. The suddenness with which she had fallen ill and the severity of her condition were shocking: In a span of just several days, she went from appearing perfectly healthy to having trouble speaking or using her hands to suffering from crippling seizures. Forty-eight hours later, the girl’s younger sister began exhibiting similar symptoms; her hospitalization was followed by those of other children in the neighborhood. Something was clearly wreaking havoc on these children’s central nervous systems—but nobody had any clue what it was.
The more local officials investigated, the more it seemed as if Minamata had been cursed with an otherworldly plague. Residents spoke of a “dancing cat disease,” where previously healthy cats began to spastically convulse and then drop dead. On more than one occasion, floating fish corpses had freckled the local port. Birds dropped from the sky without warning. By October, this mysterious new contagion had stricken forty Minamata residents, fourteen of whom had died, which made for a mortality rate several times higher than that of most cancers—and still, investigators remained stumped. It wasn’t until the following year that a common denominator emerged: All the victims had come from families that subsisted in large part on locally caught seafood. Even with that clue, it took another two years before officials determined that the cause of “Minamata disease” was toxic waste from a local factory that was poisoning the region’s fish with an organomercurial compound called methylmercury.
When scientists studied the effects of methylmercury on humans, what they found was sobering: Not only were large quantities of mercury more dangerous than previously assumed, but they were particularly dangerous for unborn children. There were, however, obvious limitations to what could be learned. The level of mercury consumed by residents of Minamata was so massive—the city’s typical resident had forty-seven times more methylmercury in his hair than the average person elsewhere, and some of the city’s inhabitants had close to two hundred times more than normal—that while the data demonstrat
ed the consequences of severe mercury poisoning, it was less useful in helping to determine what levels of mercury could be consumed safely.
In the coming decades, epidemiological studies of both man-made catastrophes and naturally occurring phenomena further clarified the danger mercury presented to humans. In 1971, nearly five hundred Iraqis died when a shipment of grain that had been treated with a methylmercury-based insecticide was stolen and sold as food. (Labels marked “DANGER” and “POISON” that were stamped on the grain sacks were printed only in English; the grain was intended for use as seed and never meant to be eaten.) Spurred in part by the Iraqi tragedy, teams of scientists conducted field studies in the Faroe Islands, off the coast of Northern Europe, where islanders’ periodic consumption of whale meat led to bursts of extreme methylmercury exposure; and in the Seychelles, an archipelago nation in the Indian Ocean, where residents’ seafood-intensive diets resulted in prolonged, low-level mercury intake. In the Seychelles, researchers from the University of Rochester found no difference in children whose mothers had consumed a significant amount of methylmercury during pregnancy; in the Faroe Islands study, there was some evidence of slight cognitive defects when children were tested at seven years of age.
All the while, the number of childhood vaccines recommended by the federal health authorities rose, from around six in the 1960s to eight in the 1980s to eleven by the end of the 1990s. Variations of a handful of those vaccines used thimerosal as a preservative. As is often the case with sweeping public policies that are implemented over many years, the officials in charge of the vaccine program tended to ignore the bigger picture: When new vaccines were under consideration, they were evaluated on their own merits, with little thought given to the collective effect of piling one thimerosal-containing shot atop another. This was partially due to the assumption that because these vaccines were so widely used, any possible side effects would already have come to light. Vaccinologists also knew that ethylmercury—the form present in vaccines—was less toxic than methylmercury, which caused the tragedies in Minamata and Iraq and was the subject of the studies in the Seychelles and the Faroe Islands.30
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