The judge, Murray Stuart-Smith, expressed sympathy with the parents of the more than two hundred different children named in the class-action lawsuit. As evidence of his concern, the judge reviewed not only the specific case of the Loveday child but also those of the other claimants. This was a fortunate outcome for the anti-vaccinators, since deeper investigation had utterly refuted the Loveday’s claims. Even a forlorn Gordon Stewart admitted, “She was not vaccine-damaged. She was damaged before.”63
The case for and against DPT as the cause of permanent neurological damage was rolled out in the trial and supported by many epidemiological and pathological studies that had been conducted over the years. The anti-vaccinators placed particular emphasis upon the publication of Miller’s highly cited and damning findings from the small Bloomsbury case.64 The pro-vaccine defense cited many other clinical trials that failed to reproduce Miller’s findings. Specifically, the outcomes reported with the small Bloomsbury cohort could not be reproduced by larger and more comprehensive analyses conducted in Sweden, Denmark, the United States, or even in England.65
After an objective and comprehensive analysis of the data, the judge issued a thoughtful verdict of more than 100,000 words (roughly the size of this book), which absolved the vaccine of any guilt in causing permanent neurological damage.66 The judge was particularly critical of John Wilson, revealing that of the fifty children Wilson had claimed were harmed by the vaccine, twenty-two had not even received the pertussis vaccine. He further suggested Wilson’s desire to make his point caused him to include these individuals to heavily bias the outcome.
The verdict also revealed that David Miller’s epidemiological study, hurriedly conducted with a small group of London physicians amidst an increasing anti-vaccine frenzy over the DTP vaccine, was fundamentally flawed and influenced by popular pressure. The judge concluded the study was hastily designed, executed, and analyzed in a desire to satiate a nervous public. Stuart-Smith unequivocally stated, “I think it can be said that this demonstrates a conscious over-anxiety to appease what I may call the vaccine-damage lobby.” Given the detailed judgement, the case was forever put to rest in the United Kingdom.
Not so in the more litigious United States, where emotional jurors, rather than objective and dispassionate judges, rendered the verdicts. Starting with the awarding of $15 million to the parents of an infant who had suffered encephalopathy after a DTP vaccination, the floodgates broke loose. The amount of damages awarded rose steadily from $25 million in 1981 to more than $3 billion in 1985.67
Because of these high-profile court cases and the media attention they attracted, public health officials became increasingly anxious over two parallel trends. First, parents were hesitant or outright defiant in not allowing their children to be immunized with the DPT vaccine. Compounding this, many traditional vaccine manufacturers were balking at continued sales, and thus liability, from the vaccine. As the vaccine manufacturers were increasingly inundated with individual and class-action lawsuits, the costs of liability insurance for their companies skyrocketed. Such concerns led many companies to remove vaccines from their portfolio of products. According to Deadly Choices, seven companies manufactured DPT in 1960, but the number dropped to three by 1982.68 The production of other vaccines was equally threatened.
Recognizing the public health dangers arising from both trends, in 1986 President Ronald Reagan signed into law a piece of legislation known as the National Childhood Vaccine Injury Act.69 We briefly touched upon this new law, which in part tasked the National Academy of Sciences with conducting a full evaluation and report on the safety and efficacy of pertussis and rubella vaccines (a subject to which we will return in the next chapter). In addition, the act essentially a priori convicted the vaccine makers by creating a compensation mechanism for families claiming damages. It also created a reporting system for vaccine reactions and toxicities and mandated better education of parents about the risks and benefits of immunization. Nonetheless, the vaccine industry was assuaged by language that limited their liability by establishing a no-fault system to compensate past and future victims of toxicities caused by legally mandated vaccination.
While the National Academy report and lawsuit absolved the whole cell pertussis vaccine of most of the toxicity associated with its use since the early 20th century, the vaccine was not without its risks, as demonstrated by the presence of some side effects. The opportunity to create a new market thus incentivized scientists across the globe, including a multinational collaboration between the United States and Japanese National Institutes of Health. This group reasoned that the broad targeting of the pertussis bacterium might unintentionally trigger unintended ferocity that was responsible for the rare inflammatory toxicities associated with whole cell vaccine.
A new approach was devised to identify the components of the bacterium that elicited the greatest protection against disease and then focus vaccine development to target a small number of proteins. These molecules are broadly known as hemagglutinins, and a race began to develop vaccines against these key parts of the virus. A Japanese team developed and tested a hemagglutinin vaccine starting in 1981.70 A pivotal study in animals and people revealed that an acellular vaccine (one that does not encompass the entire bacterium) consisting of different “components” was safe and effective.71 Specifically, the team reported that the vaccine had achieved the desired level of eliminating more than 90 percent of the toxicity associated with the whole cell vaccine. While this vaccine did prove effective, it was rushed into the Japanese market before long-term data in humans could be obtained.
Within months after the pivotal Japanese report of the new vaccine, an American team of scientists and physicians had traveled to Japan to review the findings. By this time, the acellular pertussis vaccine had been administered to more than twenty million Japanese. In a 1987 report to the Journal of the American Medical Association, the American scientists concurred with their Japanese colleagues that the vaccine was at least as effective in conveying protection in the short term (weeks or months) following immunization.72 More importantly, given the lawsuits and payouts plaguing the American vaccine manufacturers, the safety parameters of the new acellular pertussis vaccine were quite promising. They concluded their analysis of the new DTaP (reflecting diphtheria and tetanus toxioids combined with aP, referring to acellular pertussis). The report suggested the vaccine be adopted in the United States pending the results of ongoing studies in Sweden and the United States. These results were similarly encouraging, and the product was hastily launched in the United States in 1992 to much acclaim and relief from concerned parents.
The story of the pertussis vaccine might very well have ended happily here had nagging concerns about its durability not come to the fore. The specific worry was that the same limited antigenic diversity that favored greater safety of the acellular vaccine might compromise its ability to confer lasting protection. Indeed, the foundational Japanese, Swedish, and American studies were still quite fresh when the vaccine was launched in 1992. According to a 2012 article in Slate, an expert at the Centers for Disease Control and Prevention, Dr. Tom Clark, suggested fundamental flaws in the duration and perhaps sensitivity of defining protection of the new acellular disease meant “the new vaccine doesn’t actually work as long as the old one.”73 These worries were abated somewhat with a 2005 recommendation to provide eleven- to twelve-year-old children with a booster shot to reinvigorate the immune system against pertussis.
Even this measure proved ineffective, as evidenced by a series of epidemics. On June 23, 2010, the California Department of Public Health declared an epidemic emergency in what was the worst outbreak of pertussis in the United States since 1947. Altogether, 1,144 confirmed or suspected cases were identified, 51 children were hospitalized, and at least 10 died.74 A disturbing report in the Journal of the Pediatric Infectious Diseases Society revealed at least nine of ten of the sickened had been immunized at least once and many had received the booster vaccine within the
past three years, suggesting the DTaP vaccine that had been used had failed to confer lasting protection.75
Two years later, the disease returned yet again, hitting almost randomly in the United States, including California, Wisconsin, Vermont, and Washington State. Again, the epidemiological follow-up revealed the longer the time from immunization, the greater the likelihood and severity of disease. Worse still, the additional booster shots appeared to confer little if any benefit. Perhaps most telling, those children who had received the whole cell vaccine had remained protected, whereas their contemporaries immunized with the acellular vaccine did not.76 Such findings revealed that the hasty switch from the whole cell to acellular pertussis vaccine might have presaged a new susceptibility to an old killer.
Perversely, the higher the education, the more the parents tend to embrace the idea that vaccines cause more harm than good. While the associations conveyed by A Shot in the Dark and Vaccine Roulette had been thoroughly discredited in many scientific reports, these ideas have remained in the back of the minds of many parents for years.
Perhaps strangest of all, rate of vaccination has decreased the most—by 4 percent in 2009 alone—among families with health insurance as compared with the uninsured.77 These individuals can afford the vaccine but elect not to immunize their children (and, in some cases, to subvert local or state law). According to a 2010 interview by CNN with Jason Glanz, an epidemiologist with the Kaiser Permanente Institute for Health Research, “A subset of the population, typically well-educated, white and in the upper-middle class, have grown skeptical of immunizations.”78
While it would be unfair to attribute the terrifying return of pertussis simply to the actions of a small number of educated parents who refuse to immunize their children, the growing problem can more accurately be traced back to the anti-vaccinator campaign. Specifically, sensitivity about the potential side effects of the whole cell pertussis vaccine caused the biomedical community to embrace a less effective variant. The motivations of the anti-vaccinators were pure: enhancing the safety of our most precious resource: children. However, the outcome ironically created the conditions that instead endangered the lives of far more children. These choices were driven primarily by pressures exerted by Vaccine Roulette and A Shot in the Dark, which were unknowingly complicit in the deaths of future children who were not immunized or were immunized with the less effective acellular vaccine.
The ongoing experience with pertussis reveals vaccination can be a necessary trade-off between two terrible outcomes. On one hand, the whole cell pertussis vaccine can convey occasional and exceedingly rare catastrophic events. One of these terrible examples might even have been responsible for the experience of Barbara Loe Fisher’s child (though this can never be conclusively determined, given the time elapsed from whatever occurred that tragic day and the time she attributed the outcome to the DPT vaccine). On the other hand, experience has taught us that a failure to vaccinate against pertussis will inevitably kill vastly larger numbers of children. Seeking a middle ground, a combination of scientific and public health experts conspired in the most constructive sense of the word to develop the safer acellular vaccine that, in the short term, seemed just as effective as the whole cell vaccine. As often happens in life and medicine, the test of time revealed the new vaccine to be less protective. In the early years of the 21st century, we are nudging back to the catastrophic losses experienced at the beginning of the 20th.
Such realization has caused many to advocate for the creation of a new pertussis vaccine at least as safe as the acellular vaccine and with increased potency and durability of protection. In the meantime, the biomedical community and its regulators would be wise to consider the reintroduction of whole cell vaccines, which carry the risk of undesired toxicities in a few rare but tragic instances, but which have been demonstrated to confer greater protection for a larger number of children.
Sadly, the damage done by the anti-vaccinator movement was not limited to pertussis. Indeed, the power and damage exerted by organizations such as the NVIC were yet to be fully realized. This would all change with the campaign against the measles, mumps, and rubella vaccine as the cause of autism, a subject to which we will now turn.
9
Three Little Letters
This part of our story will be replete with three-letter acronyms, many of which have been unnecessarily mired in controversy. The first three-letter acronym is one well known to all parents: MMR. The acronym designates a single vaccine that prevents three of the greatest mass murderers of children: measles, mumps, and rubella. Despite the extraordinary public good that this vaccine has and continues to deliver, these three little letters have been the source of some of the most dangerous misinformation, both blatant and unintended, that increasingly threatens the lives of billions around the world.
Measles is a highly contagious infection first described in the 10th century by the Persian doctor Abubakr-e Mohammad ibn Zakariyya al-Razi (or Rhazes, as he is known in Europe).1 In the darkest days of the Middle Ages, Islamic scholars dominated virtually all sciences and promulgated knowledge that had been largely lost in Europe following the fragmentation of the Roman Empire. A published work of Rhazes, translated as The Book of Smallpox and Measles, not only conserved knowledge that had been discovered over the generations but advanced our understanding of many maladies, including a bevy of infectious diseases.2 For example, he was the first to accurately discriminate smallpox from measles, a distinction based in part on subtle differences in symptoms and epidemiology; whereas smallpox could strike people of any age, measles tended to be restricted to more youthful victims.3
Rhazes’s description of measles is rather remarkable because he might have been one of the first to not only record the disease for posterity, but may have been one of the very first people ever to witness the disease. The reason for this is that the history of measles is surprisingly short in humans. Detailed genetic analyses have recently revealed that measles jumped from cattle to humans at almost the exact moment Rhazes was recording it.4 Despite the relatively recent jump of measles to man around the 10th century, its parentage had been a legendary source of plague for millennia. It seems that what we today call measles is but a few mutations separated from a disease known as rinderpest. Rinderpest is a plague that consumes cattle, antelopes, giraffes, and other hoofed animals. Historic fascination with the disease is based in part on the fact that death is almost certain following infection. Because of its rapid spread, rinderpest could quickly decimate food sources for entire civilizations. For example, rinderpest virus is believed to be one of the “ten plagues” inflicted upon the Egyptian pharaoh as described in the book of Exodus.5, 6 In addition, an outbreak of the disease in Napoleonic Europe added famine to the list of miseries suffered during that bloody period.
Diseases that are new to humans tend to be the most dangerous, as they have not yet evolved to form a mutually beneficial long-term relationship with their prey. One way of viewing this is that the pathogen seeks to keep its quarry (you and me) alive long enough to ensure its propagation to future generations of victims. On one hand, the microbe will undergo evolution such that those variants that improve their ability to spread to others will win out over those that might be deadlier and kill prior to being passed on. At the same time, genetic variation in people may distinguish those individuals who are more susceptible to the disease than others. Consequently, the evolution of measles and humans has not yet reached a point where the disease has reached a truce with humanity to ensure the survival of both species.
As evidence of its destructive power, measles has been responsible for the deaths of at least 200 million people over the past century and a half alone.7 As we saw at the beginning of the book, the introduction of smallpox to the New World was devastating to its native inhabitants, and measles soon conveyed the coup de grace to entire societies. One illustration is the experience suffered by the native peoples of Cuba in 1529. Shortly after the arrival of Columbus, the i
slands of the Caribbean began to be decimated by the spread of smallpox. This began in earnest in Cuba in 1518 and is estimated to have killed as many as one third of the population of that island and those surrounding it.8 Just as the population was beginning to recover, measles visited the island. In 1529, the disease is estimated to have killed two thirds of the remaining native population.9 Similar outbreaks occurred throughout the world, and the devastation of measles extended beyond the Caribbean into both American continents, Hawaii, the South Pacific, and isolated peoples in the North Atlantic, to name but a few.10, 11, 12
The symptoms of measles include a very high fever accompanied by a cough, runny nose, and red, swollen eyes. Within a few days, an infected individual will develop a series of small, white spots that resemble “grains of bright, white salt set on a wet background” on the inside of the cheek towards the back of the mouth.13 This rather unique symptom was first described in 1896 by the New York physician Henry Koplik and is more than esoteric, because the presence of Koplik spots is an early predictor of a greatly increased contagiousness that will follow over the next few days.14 Consequently, the identification of Koplik spots in an infected child provided an early means to isolate the child and thus limit the spread of the disease to siblings and playmates.
A day or two after the emergence of Koplik spots, a series of red bumps will start to emerge on the skin, often beginning on the face behind the ears and near the hairline. These bumps grow in number and eventually merge into a flattened and itchy rash that can coat the body’s surface from head to toe. This type of rash is also associated with other diseases (including Ebola and other hemorrhagic fever viruses) and provoked the name for scarlet fever. One feature distinguishing measles from these equally horrific maladies is that the rash often changes color from red to brown. For those lucky enough to have a less severe infection or some immunity (albeit not enough to prevent the disease), the brown rash will fade, and all that remains is a bad memory of the terrible itching. The most likely survivors are those infected while young, who tend to fare better. For older children and adults, many severe complications greatly increase the morbidity and mortality caused by measles.
Between Hope and Fear Page 29
