Deadly Choices: How the Anti-Vaccine Movement Threatens Us All - Paul A. Offit (2010)
Chapter 3. A Crude Brew
Nothing in life is to be feared—only to be understood.
At the beginning of DPT: Vaccine Roulette, Lea Thompson asked Gordon Stewart to describe the pertussis vaccine. Stewart said it was “a crude brew of those bacteria and all their growth products.” Stewart’s description was an understatement.
Bordetella pertussis was first grown in a nutrient-rich broth in 1906. In the 1930s, Pearl Kendrick and Grace Eldering made a vaccine by simply killing pertussis bacteria with carbolic acid, an antiseptic. In 1939, they tested it. Kendrick and Eldering studied more than 4,000 children, giving their vaccine to half; during the next four years, they watched to see who got sick and who didn’t. The results were clear: whereas 348 unvaccinated children got whooping cough, only 52 vaccinated children suffered the disease. Ten years later, in 1948, the pertussis vaccine was combined with diphtheria and tetanus vaccines to make DTP. Although diphtheria, tetanus, and pertussis vaccines were given in the same syringe, the vaccines were quite different. That’s because scientists had a much better understanding of how diphtheria and tetanus caused disease.
Like pertussis, diphtheria is caused by a bacterium: Corynebacterium diphtheriae. The bacterium causes a large, painful membrane to form on the back of the throat that can suffocate its victim; it also makes diphtheria toxin, which harms the brain, heart, and kidneys. (In the early 1900s, diphtheria was one of the biggest killers of young children.) Protection against diphtheria is afforded by immunity to this single toxin. So, when researchers wanted to make a diphtheria vaccine, all they had to do was grow toxin-producing bacteria in nutrient fluid, filter the bacteria out of the fluid, and leave the toxin behind. Then they inactivated the toxin with chemicals. Inactivated toxin is called toxoid.
Tetanus vaccine is made exactly the same way. Tetanus, or lockjaw, is caused by the bacterium Clostridium tetani. As with diphtheria, tetanus bacteria make just one harmful toxin—and protection against tetanus is afforded by immunity to that toxin. Accordingly, diphtheria and tetanus vaccines each contain only a single protein.
Making a pertussis vaccine, on the other hand, hasn’t been easy. That’s because the pertussis bacterium doesn’t make just one protein that causes disease. It makes many; at least nine pertussis proteins play an important role in infection. Some of these proteins are part of the structure of the bacteria; other proteins, like diphtheria and tetanus toxins, are secreted by bacteria. When Kendrick and Eldering were making their vaccine, they didn’t know how many pertussis proteins caused disease. So they took bacteria, grew them in nutrient fluid, and treated the whole concoction with carbolic acid. Their vaccine, made using whole, dead pertussis bacteria, contained more than three thousand pertussis proteins.
When Kathi Williams, Jeff Schwartz, and Barbara Loe Fisher organized Dissatisfied Parents Together, the process of making pertussis vaccine wasn’t much different from that used by Kendrick and Eldering forty years earlier. Because the vaccine was so crudely made, it had a higher rate of side effects than any other vaccine. To put this in perspective, in 1982, when Lea Thompson galvanized the public with Vaccine Roulette, in addition to the DTP vaccine, children received the combination measles-mumps-rubella (MMR) vaccine and the oral polio vaccine. Measles vaccine contains ten viral proteins; mumps, nine; rubella, five; and polio, fifteen. This meant that the total number of immunological challenges in the measles, mumps, rubella, polio, diphtheria, and tetanus vaccines combined was forty-one, about a hundredth the number contained in the pertussis vaccine alone.
Pertussis vaccine was the only vaccine given to American children made from whole, dead bacteria. (Courtesy of Dennis Kunkel Microscopy/Corbis.)
By the early 1980s, only one study in the United States had carefully examined the side effects of pertussis vaccine. During her program, Lea Thompson introduced the researcher who did it: Dr. Larry Baraff of the UCLA Medical Center. Baraff explained why he had done the study: “Because the Food and Drug Administration was concerned that this sort of public panic might spread [from England] to the United States, they wanted to document that the vaccine was safe and not associated with severe consequences.”
Baraff’s findings were striking. Of every thousand children given pertussis vaccine, eighty suffered redness and swelling at the site of injection (more than an inch wide); about five hundred had pain; five hundred had fever; three had fever greater than 105 degrees; three hundred felt drowsy; five hundred were fretful; twenty didn’t want to eat; ten cried for more than three hours (and as long as twenty-one hours); and one had an unusual, high-pitched cry (Kathi Williams’s child suffered this side effect). Further, of every ten thousand children vaccinated, six suffered seizures with fever and six had decreased muscle tone and responsiveness that lasted for a few hours. (This side effect, called Hypotonic-Hyporesponsive Syndrome, can cause children to be pale and limp for hours—devastating for any parent to watch. Barbara Loe Fisher’s child most likely suffered this problem.) Baraff explained that these side effects were the result of the archaic technology used to make the vaccine. “I don’t think that this is the type of vaccine that would be produced today,” he said. “If this vaccine were produced in 1980, instead of in the 1930s and ‘40s, there would be a different type of technology available and we would make a more purified vaccine.” Baraff was right. Taking advantage of advances in protein chemistry and protein purification, by the mid-1990s, safer pertussis vaccines—containing only two to five pertussis proteins instead of three thousand—were licensed.
Although transient side effects following pertussis vaccine were common, that wasn’t at issue. The important question raised by Vaccine Roulette was whether the vaccine could cause permanent harm, such as epilepsy and mental retardation. Answering this question isn’t as easy as it seems. That’s because every year in the United States, in England, and throughout the world, children suffer epilepsy and mental retardation; this has been true for centuries, well before the pertussis vaccine was invented. Also, symptoms of epilepsy and retardation often occur in the first year of life, the same time that children are receiving three doses of vaccine. Given the widespread use of pertussis vaccine, most children destined to develop seizures or mental retardation anyway would likely have received it, some within the previous twenty-four or forty-eight hours. So, the only way to figure out whether the vaccine was the problem was to study thousands of children who did or didn’t get it. If the vaccine were responsible, the risk of epilepsy or retardation would be greater in the vaccinated group. At the time of Vaccine Roulette, only one large-scale study of children had been completed: David Miller’s. The next fifteen years, during which other investigators examined this question, were not kind to David Miller’s study.
The first flaw with the notion that pertussis vaccine caused brain damage was that it didn’t make biological sense. Anyone working in a hospital knew that natural pertussis infection could cause brain damage because of decreased oxygen in the bloodstream caused by unrelenting coughing. But the pertussis vaccine—made of killed bacteria that didn’t grow in the lungs or windpipe—didn’t cause coughing.
So what could have caused brain damage? One prevalent theory was that the pertussis vaccine contained small amounts of endotoxin : part of the surface of a variety of bacteria (including pertussis) and a very potent poison. In 1978, a researcher named Mark Geier published a paper claiming that commercial preparations of pertussis vaccine contained small quantities of endotoxin. Because even a little endotoxin can have devastating effects, Geier reasoned that severe reactions to pertussis vaccine might be caused by endotoxin. The problem with this logic is that endotoxin causes brain damage by inducing a cascade of events that includes fever, rapid heart rate, chills, low blood pressure, shock, and decreased oxygen to the brain. Indeed, the one symptom that occurs in everyone experimentally inoculated with endotoxin is fever. But many children with seizures and retardation following pertussis vaccine never had fever. And pertussis vaccine didn’t cause low blood pressure or shock, another common response to endotoxin.
Epidemiological studies didn’t support Miller’s study, either.
In 1956, the Medical Research Council in England studied more than thirty thousand children for two years. It couldn’t find even one who had suffered brain damage as a result of the pertussis vaccine.
In 1962, Bo Hellström at the Karolinska Institute in Stockholm studied eighty-four healthy infants who had received DTP and later suffered high fever or decreased responsiveness. Hellström performed electroencephalograms on children six and twenty-four hours after vaccination, reasoning that if the vaccine was affecting the brain, then the EEGs, which can detect even slight alterations in brain wave activity, should be abnormal. But they weren’t. All the children had perfectly normal EEGs.
In 1983, two years after David Miller’s study was published, T. M. Pollack and Jean Morris, researchers at the Public Health Laboratory and Department of Community Medicine in London, published their own study. They analyzed 134,700 children in the North West Thames Region of England who had received three doses of DTP and compared them to 133,500 children who had received DT alone. Their study enabled them to isolate the effect of the pertussis component of the vaccine. They, too, couldn’t find what David Miller had found.
Also in 1983, three neuropathologists in England studied the brains of twenty-nine children whose deaths had been blamed on pertussis vaccine. Some had died within a week of getting the vaccine; others had suffered epilepsy, mental retardation, or physical disabilities. The investigators were looking for anything that tied these cases together—some indication that the vaccine had caused the problem. But no distinct pathological finding linked the cases.
In 1988, researchers in Denmark took advantage of a natural experiment. Before April 1970 children in Denmark were vaccinated with the DTP vaccine at five, six, seven, and eighteen months of age. But after April 1970 they were given the pertussis vaccine at five and nine weeks and again at ten months of age. Investigators reasoned that if epilepsy were a consequence of receiving pertussis vaccine, then the onset of seizures should change with the changing schedule. But it didn’t.
Six years after the airing of Vaccine Roulette, a study was finally performed on American children. In 1988, researchers from the department of epidemiology at Harvard’s School of Public Health and the Group Health Cooperative of Puget Sound in Seattle examined the records of more than thirty-five thousand children. They wanted to determine whether epilepsy was more common in those recently vaccinated. It wasn’t.
Two years later, Marie Griffin and colleagues from Vanderbilt University published a study of more than thirty-eight thousand children in Tennessee, looking for a relationship between DTP and brain damage. Again, they were unable to find what David Miller had found.
The number, reproducibility, and consistency of these studies prompted a response from public health agencies. In 1989, the British Pediatric Association and the Canadian National Advisory Committee on Immunization concluded that pertussis vaccine had not been proved to cause permanent harm.
In 1990, the same year Marie Griffin published her paper, Gerald Golden—Shainberg professor of pediatrics, director of the Boling Center for Developmental Disabilities, and professor of neurology at the University of Tennessee—reviewed the evidence. Golden was unequivocal in his conclusions. “A syndrome of pertussis vaccine encephalopathy was first reported fifty-six years ago,” he wrote, referring to the 1933 report of two deaths following pertussis vaccine in Copenhagen. “Analysis of the recent literature, however, does not support the existence of such a syndrome and suggests that neurological events after immunization are chance temporal associations.” James Cherry, the pediatric infectious diseases specialist from UCLA, seconded Golden’s conclusions regarding the vaccine-brain damage link, writing that it was “time to recognize it as the myth that it is.”
In 1991, the Institute of Medicine—an independent research institute within the U.S. National Academies of Science—concluded that the association between pertussis vaccine and brain damage remained unproved. An ad hoc committee for the Child Neurology Society agreed, stating, “Case reports have raised the question as to whether there is an association between pertussis vaccine and progressive or chronic neurological disorders, but controlled studies have failed to prove an association.”
More evidence mounted.
In 1994, researchers from the University of Washington and the Centers for Disease Control and Prevention teamed up to do yet another study. They evaluated more than two hundred thousand children in Washington and Oregon and concluded: “This study did not find any statistically significant increased risk of onset of serious acute neurological illness in the seven days after DTP vaccine.”
On March 10, 1995, seizure disorder following DTP vaccine was removed from the Vaccine Injury Compensation Program’s list of compensable injuries because “no medical evidence” existed to support the presumption—ironic, given that the program was born of this specific concern.
Finally, in 2001, researchers working with a group of health-maintenance organizations performed the clearest, most definitive study to date. Using computerized records, investigators analyzed the occurrence of seizures in three hundred and forty thousand children given DTP compared with two hundred thousand children who received no vaccine. They concluded: “There are significantly elevated risks of febrile seizures after receipt of DTP vaccine, but these risks do not appear to be associated with any long-term, adverse consequences.” (Although frightening to witness, seizures caused by fever, which occur in as many as 5 percent of young children, don’t cause permanent harm.)
No one had been able repeat David Miller’s study—remarkable, given its impact.
Miller and his team had worked hard. They had evaluated data from 1,182 children accumulated from July 1, 1976, to June 30, 1979. Further, their study wasn’t limited to London or England; they had also evaluated all children with neurological illnesses in Scotland and Wales. Miller and his team had assessed reactions to more than two million doses of pertussis vaccine; and they’d spent millions of dollars doing it. No study of the vaccine had ever been so thorough or so large. So why weren’t any subsequent investigators able to find what David Miller had found? The answer wouldn’t come from a scientific laboratory, or an academic institution, or an independent research organization. It would come, surprisingly, from a British courtroom.
In the United States, hundreds of lawsuits resulted in many trials. In England, on the other hand, the DTP scare resulted in only three trials. The last would show precisely what had gone wrong with David Miller’s study.
The first trial took place in Edinburgh, Scotland, in 1985, centering on a little boy named Richard Bonthrone.
Bonthrone had received his first dose of DTP vaccine when he was four months old. Three months later, he received his second. Nine days after that, he had the first of many seizures. At the time of the trial, Richard was nine years old with the mental age of a six-month-old. He ate only liquid food and couldn’t do anything for himself. The judge, Lord Jauncey, wrote that Richard’s “only enjoyment of life appears to be in recognition of his mother’s voice and in travel by motor car.” Richard’s parents, John and Iris, sued their doctor, the Department of Health, and a visiting nurse for £145,000.
Two experts testified at Bonthrone’s trial. Dr. John Stephenson, a pediatric neurologist from the Hospital for Sick Children in Glasgow, said that while he accepted that DTP precipitated seizures following fever, he “was unconvinced that permanent brain damage resulted.” Next up was David Miller, who said, “The risk of developing encephalopathy nine days after being vaccinated [is] so small as to be incapable of statistical measurement.” Judge Jauncey ruled in favor of the defense. But the Bonthrone trial hadn’t refuted Miller’s study. Miller had never claimed that DTP caused harm nine days after a dose, only within three days of a dose.
Another trial quickly followed.
Johnnie Kinnear was fourteen months old when he received a dose of pertussis vaccine. According to his mother, Johnnie had a seizure seven hours later. The next morning, she took her son to the doctor who dismissed her concerns, saying it was “normal for children to have reactions” and there was “nothing to worry about.” But the seizures continued, every day for many months. The Kinnears sued the Department of Health, their doctor, the North West Thames Health Authority, and the Wellcome Foundation, which manufactured pertussis vaccine in England. The legal aid board intervened, allowing the suit to proceed only against the health authority and the doctor. The Wellcome Foundation was excused in part because it was one of several manufacturers of pertussis vaccine in England (Glaxo and Lister also made the vaccine); and it was unclear which brand Kinnear had received. But, in an unprecedented move, Wellcome decided to enter the case anyway—in essence, choosing to be sued. Wellcome was tired of the negative press surrounding pertussis vaccine and wanted to settle the issue once and for all. It, too, wanted its day in court. This was the first time that a drug maker in England had defended the safety of one of its products in a full court hearing.
The Kinnear trial began on March 17, 1986, and included many experts in the fields of virology, epidemiology, and statistics; among them were John Wilson, whose paper had ignited fears about the vaccine in England; Gordon Stewart, who had been prominently featured in Vaccine Roulette; and David Miller. The judge in the trial was Murray Stuart-Smith. Fifty-seven years old and the father of six, Stuart-Smith had graduated with first-class honors from Cambridge University. He would soon become a celebrated jurist and acquire the title of “Sir.” (Stuart-Smith would later sort out the tragedy that occurred at Hillsborough Stadium on April 15, 1989, when ninety-six Liverpool football fans were killed in a melee.)
The lawyer for the Kinnears was Julian Priest, who began by taking his star witness, Gordon Stewart, through early case reports. Stewart talked about the 1933 Copenhagen report, which described two Danish children who had suddenly died after receiving vaccines. He talked about the study from Harvard Medical School by Byers and Moll, who had reported fifteen children with irreparable damage following pertussis vaccine. He talked about Justus Ström’s paper from Sweden claiming that the vaccine caused permanent damage in one in thirty-six hundred children, far greater than the one in one hundred thousand later claimed by David Miller. Stewart concluded, “No matter how scrupulously the vaccine was prepared, one could not avoid including toxic products.”
The Kinnear case had two large holes. The first problem was a discrepancy between the mother’s testimony and the medical record. Kinnear’s mother testified that her son’s seizures began seven hours after he received DTP. But the medical record showed that Johnnie Kinnear’s first seizure had occurred five months, not seven hours, later. The contradiction was undeniable, causing Judge Stuart-Smith to say, “The mother’s evidence was crucial as to the date of onset of symptoms, which she said occurred very shortly after the vaccination. Unfortunately, she was not telling the truth. And this was apparent to all, including the plaintiff’s advisors.”
The second problem was Gordon Stewart. No one’s reputation would suffer more from the Kinnear trial than his. During the trial, Stewart had repeatedly misquoted details of David Miller’s study. But his greatest embarrassment came during his discussion of another study. Stewart had stated: “Levine and Wenk described a hyperacute allergic encephalomyelitis which occurred in children who appeared to have been sensitized by a previous dose of pertussis vaccine.” Anthony Machin, the Wellcome Foundation’s attorney, asked Stewart, “Do you remember anything about the age of the children?” “No, not offhand,” replied Stewart. Machin pressed on: “Or the ethnic origin?” “No, I cannot remember that,” said Stewart. “It was an American study, I know that.” Machin then handed the study to Stewart, who looked through the paper and then up at Machin, embarrassed. Stewart apologized for his mistake. The study hadn’t been done on children; it had been done on rats. The gaffe marked the end of Gordon Stewart’s role in damning pertussis vaccine. During a subsequent trial, he was labeled “an evidential liability.” Although the Kinnear trial took twenty-nine days, included many witnesses, and cost the government £1 million to litigate, it ended without a verdict.
The litigation, however, didn’t end.
The trial that ended all pertussis vaccine trials in England began on February 1, 1988. Again the judge was Lord Justice Murray Stuart-Smith. The plaintiff was Susan Loveday, a mentally disabled seventeen-year-old who lived in Bradford-upon-Avon in Wilshire. Susan’s story was similar to the others. In 1971, George Renton, Susan’s doctor, administered the first dose of DTP after which Susan “had a high temperature and local inflammation and was sleepy but crying a great deal.” Her mother noticed that she wasn’t as lively and that “one eye seemed odd.” One year later, Renton gave Susan her second dose of DTP. This time she “had a similar reaction and screamed all night.” One month later, she was referred to another pediatrician who noticed that she looked “rather odd and hypotonic [floppy].” Then Renton gave her a third shot of DTP. By the time she had her day in court, Susan Loveday was severely retarded.
Loveday was the lead case in a class-action lawsuit that included two hundred other children with similar stories. Most had been gathered by Rosemary Fox, the head of Britain’s Association of Parents of Vaccine-Damaged Children. Unfortunately, as had happened with Johnnie Kinnear, under closer inspection Susan Loveday’s story started to unravel. It shouldn’t have come as a surprise. In fact, when Rosemary Fox had sent out questionnaires to find vaccine-damaged children, she had weeded out Loveday’s story as improbable. Even Gordon Stewart, an unwavering advocate for the cause, said, “She was not vaccine-damaged. She was damaged before.”
Stuart-Smith had learned his lesson from the first trial. Rather than simply examining the merits of Loveday’s claim to see if it was a true case of vaccine damage, he decided to divide the trial into two parts. The first would be devoted to determining whether pertussis vaccine could cause permanent harm. If the answer was yes, the second part would determine who qualified for compensation. As in the Kinnear trial, the Wellcome Foundation voluntarily joined in. Wellcome wanted to see the data on which David Miller had based his conclusions—to see the stories of the children who were allegedly harmed by pertussis vaccine.
The case of Loveday v. Renton and Wellcome Foundation Ltd. took four months, involved nineteen expert witnesses, and cost more than £1 million to conduct. The judgment was more than one hundred thousand words long and included fourteen chapters and six appendices. The verdict was so long that it took Stuart-Smith two full days to read it; and so detailed that it left little room for appeal. Although the Loveday trial considered a great many issues, it was a trial of one study and one study only: David Miller’s. Under the bright lights of Justice Stuart-Smith’s courtroom, Miller’s study fell apart.
Stuart-Smith began the trial by expressing sympathy for parents who believed their children had been damaged by DTP. “For many of [the parents] the answer must seem obvious,” he said. “Their child is vaccinated and within a relatively short time thereafter, perhaps hours or days, [he] becomes seriously ill. [He] may have convulsions, become unconscious, show signs of paralysis; there may be prolonged screaming or vomiting. Later, there are signs of permanent mental handicap; blindness, deafness, paralysis or motor impairment, epilepsy, severe mental retardation. The one event must have caused the other, especially when the time interval between vaccination and onset of symptoms is measured in hours rather than days.” But Stuart-Smith wasn’t going to be swayed by temporal associations. Quoting Samuel Johnson, he said, “It is incident I am afraid, in physicians above all men, to mistake subsequences for consequences.” Then he elaborated. “Where given effects, such as serious neurological disease or permanent brain damage, occur with or without pertussis vaccination, it is only possible to assess whether the vaccine is a cause, or more precisely a risk factor, when the background incidence of the disease is taken into account. The question therefore is, does the effect occur more often after pertussis vaccination than could be expected by chance?”
By quoting Samuel Johnson, Stuart-Smith had hit on the central issue in the trial: the power of anecdote. For the parents of Richard Bonthrone, Johnnie Kinnear, and Susan Loveday the issue was clear. Their children had been fine until they’d received the pertussis vaccine. But the mere fact that one event follows another doesn’t necessarily mean that it caused the other. (Unfortunately, it’s hard to fight anecdote with statistical data. An emeritus professor at Duke University School of Medicine tells the story of a friend who took his four-month-old son to get a DTP vaccine. He waited and waited in line, eventually tiring and going home, his child never having received the vaccine. Several hours later the father went to wake the child, only to find that he had died, presumably from Sudden Infant Death Syndrome. One can only imagine what the father would have felt if his son had received DTP several hours earlier. Presumably, no study would have convinced him of anything other than that the vaccine had killed his son.)
Stuart-Smith began by singling out the man who had started it all: John Wilson. After acknowledging that Wilson’s paper had been circumspect and “tentative in its conclusions,” the judge was angry that he had included two children in his report who had never received pertussis vaccine. “Dr. Wilson is entirely convinced that the vaccine on rare occasions causes brain damage,” said Stuart-Smith. “He formed this view at a very early stage and he is completely committed to it. An example of this, small in itself but perhaps revealing, is to be found in the two DT cases in [his paper]. When he gave his evidence Dr. Wilson had forgotten that he had previously known that these were DT and not DTP cases, and so he stated at first that they were DTP. I was not convinced by his explanation that the matter was of no consequence and did not affect the thrust of the article. I think he had forgotten it because it was inconvenient.” Chastened, John Wilson would never again carry high the torch that pertussis vaccine caused brain damage.
Then Stuart-Smith turned his attention to David Miller. Miller was certainly aware of the furor surrounding his study; aware that Rosemary Fox had formed the Association of Parents of Vaccine-Damaged Children; aware that politicians had rallied in support of these children; aware that several doctors, such as Gordon Stewart, had become vocal advocates for the cause; and aware that the press and public knew full well that the national government had funded his study. Miller didn’t want to appear to have whitewashed the issue. So he bent over backward to report any possible problems with the vaccine. Earlier in the trial, one of Miller’s collaborators had stated, “Because it was essential that pertussis vaccine should not appear from this study safer than it actually is, steps were taken at every stage to ensure that the results would overestimate rather than underestimate the risks.” An example of this type of bias appeared in instructions to physicians. “If there is doubt, code the worst picture,” they read. David Miller described what it was like to do a study under the bright lights of the press and public. “We were extremely anxious,” he said. “One has to remember the context in which the study was done, which was that there was a great deal of alarm about the possibility of there being damage associated with the vaccine.... It was extremely important that our results were not subject to criticism by those who might say that we were endeavoring to avoid demonstrating the possibility of a neurological damage associated with a vaccine.... It was very important that we avoided that kind of accusation.” Stuart-Smith was unsympathetic: “I think it can be said that this demonstrates a conscious over-anxiety to appease what I may call the vaccine-damage lobby, which may have led to decisions being biased against the vaccine.”
There were bigger problems. Stuart-Smith was unhappy that Miller’s study, due to political pressure, was published prematurely. “Unfortunately, owing to what Professor Miller described as political though not party-political pressure, the report of the [study] had to be published before the data were complete. As a result, it deals only with the first one thousand of the total of 1,182 cases. More importantly, the data relating to the final outcome were incomplete.” When the data were complete, when the full follow-up was concluded, and when the details of all of the cases were finally revealed, a very different picture emerged.
In his study David Miller maintained that seven children had developed brain damage within a week of receiving DTP. But a closer look showed that these cases weren’t what they were claimed to be. Three of the children had been incorrectly labeled as brain damaged when in fact they were normal both before and after vaccination. Three others had suffered viral infections and one Reye’s Syndrome (a severe neurological problem found later to be caused by aspirin, not vaccines). Miller’s conclusions lay in ruins.
In March 1988, Stuart-Smith delivered his verdict: “On all the evidence, a plaintiff had failed to establish, on a balance of probability, that pertussis vaccine used in the United Kingdom and administered intramuscularly in normal doses could cause permanent brain damage in young children.” David Salisbury, currently director of immunization for England’s Department of Health, remembered the impact of Stuart-Smith’s verdict: “I thought that for a judge who was not a trained epidemiologist it was an extraordinarily insightful analysis of all of the available evidence. The [verdict] clearly gave us much more authority to be clear about the risks of pertussis and the risks of not being vaccinated.”
No other trials against pertussis vaccine would ever appear in a British courtroom. Soon after Judge Stuart-Smith concluded in England that pertussis vaccine didn’t cause permanent brain damage, Judge John Osler made an identical decision in a landmark case in Canada. Osler concluded that while the “post-pertussis theory was popular some years ago,” further study and technology refuted the contention.
Stuart-Smith’s trial had gone a long way toward putting to rest the notion that pertussis vaccine caused epilepsy and mental retardation. But it never addressed the real cause or causes of the problem. That’s because science hadn’t advanced far enough to answer the question of what caused seizures. During the next two decades, that would change. And the answer wouldn’t come from England, where the notion that pertussis vaccine caused brain damage had first gained international attention, or from the United States, where vaccines had almost been eliminated by lawsuits. Rather, it would come from a relatively unknown researcher on the east coast of Australia.
Seizures are more common than most people realize, typically occurring in the first year of life. Indeed, every year as many as one hundred and fifty thousand children in the United States develop seizures caused by fever. Most of these children never have seizures again. However, every year about thirty thousand children, whose first seizure may or may not have been associated with fever, develop epilepsy. When Lea Thompson was putting the pertussis vaccine on trial in the media, or Paula Hawkins in Congress, or Stuart-Smith in a British courtroom, seizure disorders in infants were not very well understood. But, during the next twenty years, neurologists made tremendous strides in sorting out different seizure types based on clinical symptoms, EEG patterns, age of onset, and response to therapies. More important, with the availability of genetic probes, the specific genes that caused many of these epilepsy syndromes were found. As of 2009, the genetics of at least fifteen different epilepsy syndromes had been identified.
It was with this knowledge—and these genetic tools in hand—that Samuel Berkovic, director of the Epilepsy Research Center, scientific director of the Brain Research Institute, and the Laureate Professor in the department of medicine at the University of Melbourne, decided to revisit the question of what was causing epilepsy and mental retardation in children after DTP vaccine. Berkovic was particularly interested in a type of epilepsy called Dravet’s Syndrome: a genetic disorder. First described by Charlotte Dravet in 1978, the syndrome included children who had seizures and mental retardation exactly like those described in Lea Thompson’s program. But Charlotte Dravet had described her syndrome in children, not adults. And Berkovic only took care of adults. “I just vividly remember seeing in the clinic this woman who was in her mid-forties,” he recalled. “I had treated her for fifteen or twenty years. [She had] a very devoted mother who would bring her to see me. And it’s actually hard to recognize [Dravet’s Syndrome] in adults because the clinical features have their evolution in the first couple years of life. Then the penny dropped. This is Dravet’s Syndrome!” Samuel Berkovic was the first person to postulate that adults with seizures and retardation who were labeled vaccine-damaged as children might instead be suffering from Dravet’s. He remembered the emotional burden that the mother had carried for more than forty years: “Why did she get her daughter vaccinated? If only she hadn’t gotten her vaccinated this terrible thing wouldn’t have happened. And she carried the guilt and grief of all of this. So we started looking aggressively to collect the cases.”
Samuel Berkovic, a neurologist at the University of Melbourne, was the first to figure out what had caused seizures and mental retardation in the children featured in Lea Thompson’s DPT: Vaccine Roulette. (Courtesy of Dr. Samuel Berkovic.)
In 2006, Samuel Berkovic evaluated fourteen people with severe epilepsy and mental retardation. All had developed their first seizures between two and eleven months of age; all had received the pertussis vaccine within the previous forty-eight hours; and several had been compensated for damage allegedly caused by the vaccine. Some had had fever following the vaccine, but most hadn’t. Berkovic believed that all suffered from Dravet’s Syndrome. So he looked to see whether they had a genetic defect that caused the problem. He found that eleven of the fourteen had a defect in the gene that regulates the transport of sodium in brain cells. (The specific gene is called SCN1A; and the specific disorder, a sodium channel transport defect.) Recognizing that vaccines can’t change a child’s genetic makeup—and that 100 percent of children with SCN1A defects will have seizures and mental retardation independent of whether they receive vaccines—Berkovic wrote, “The identification of a genetic cause of encephalopathy in a particular child should finally put to rest the case for vaccination being the primary cause.” In the last few sentences of his landmark paper, Samuel Berkovic made a plea on behalf of children with epilepsy: “Correct diagnosis will reassure the family as to the true cause, remove the blame of having vaccinated the child, direct appropriate treatment, and allow realistic planning for prognosis.”
Berkovic was surprised by the reaction to his paper. “I was very excited about this [work],” he recalled. “I thought it was one of the most, if not the most, important thing I’d ever done.” Following publication, several commentaries praised the work, one calling it the most outstanding paper of 2006. “Most of my neurologist colleagues thought that the paper was really important because they’re the people that see these cases directly. But among the vaccine community I couldn’t get any traction. We were trying to get a much bigger study together and collect more cases and we just couldn’t. I got a bit dispirited and gave up. Why didn’t it get traction? I don’t know. It befuddled me. Maybe it’s because it was something from a bygone era.”
After Berkovic’s paper, it was clear that all the time spent by parents to get health officials to admit that pertussis vaccine had permanently harmed children, all the money spent by pharmaceutical companies to compensate alleged victims, all the work of lawmakers to create a system to deflect lawsuits away from these companies, and all the ink devoted by the media to support these children and their parents had been an enormous diversion from the real cause of the problem.
Although parents of children with epilepsy and mental retardation were wrong in believing that pertussis vaccine was at fault, they were right in several respects: First: it’s likely that their children had appeared perfectly normal before they received the vaccine. Many infants with epilepsy and retardation syndromes have no symptoms for the first few months of life.
Second: many doctors had assumed that seizures following DTP had been febrile seizures and falsely reassured parents that these were common and nothing to worry about. During Paula Hawkins’s hearings into the safety of the pertussis vaccine, Marge Grant, whose son Scott had been prominently featured in Vaccine Roulette, submitted written testimony. “Before I go into the grave injustice we’ve encountered through the entire court system, including the U.S. Supreme Court,” she wrote, “I wish to re-emphasize that Scottie did NOT display a ‘fever’ after any of the shots.” Consistent with Grant’s testimony, most of the children in Berkovic’s study hadn’t had seizures that were precipitated by fever, either.
Third: parents were right in pointing out that no one else in the family had had epilepsy. During Vaccine Roulette, Marge Grant took aim at the Food and Drug Administration (FDA), elicited the support of Jimmy and Rosalynn Carter, and skewered pharmaceutical companies for misrepresenting, hiding, or shredding data. But during Hawkins’s hearing, Grant also directed her anger toward doctors. “As I look back at this nightmare and the severity of Scott’s injury,” she recalled, “I do not believe he is just one unusual, obscure case, who displayed almost no early symptoms, yet suffered profound permanent damage. I am convinced there is an extremely fine line, such as in Scott’s instance, where major vaccine problems exist, but actually go undetected by parents until much later, when they are finally told the child’s developmental deficits must be genetic. Can you imagine the trauma that must hit a parent? If they felt it was genetic, they would probably never have another child.” Grant knew that neither her own nor her husband’s family had a history of epilepsy or retardation. But she hadn’t understood that not all genetic problems are inherited. Samuel Berkovic subsequently addressed this issue in his study. He noted, “In nine of the eleven patients with SCN1A mutations for whom samples from both parents were available, the mutations were absent in parental DNA and thus arose de novo.” This meant that the genetic mutation had occurred spontaneously during conception.
Soon after Samuel Berkovic published his paper, Simon Shorvon and Anne Berg, researchers in England and the United States, wrote an editorial discussing the importance of its findings. “If properly communicated,” they wrote, “the Australian findings should also do much to improve the public’s understanding of the true risks and the safety of this vaccine.” During the pertussis scares in England and the United States, scares that spilled over into virtually every developed country in the world, thousands of media outlets falsely alerted parents to the harm caused by pertussis vaccine. But when Samuel Berkovic finally found the answer to the question of what had actually caused the problem, no one noticed. Not a single newspaper, magazine, or radio or television program carried the story.