The result was predictable. Pharmaceutical companies abandoned vaccines. In 1960, seven companies made DTP. By 1982 only three remained: Connaught Laboratories of Swiftwater, Pennsylvania; Lederle Laboratories of Pearl River, New York; and Wyeth Laboratories of Philadelphia. On June 13, 1984, Wyeth announced it would no longer be distributing DTP. Later that summer, Connaught announced it was unable to get liability insurance and would stop making DTP vaccine for American children. Following Connaught’s announcement, Lederle was the only company left standing.
On December 19, 1984, James O. Mason, director of the Centers for Disease Control and Prevention, appeared before the House Subcommittee on Health and the Environment. The committee wanted to know how much DTP vaccine was available. The situation, as Mason described it, was desperate. “On November 27, [1984,] Lederle informed us that they were having some production difficulties and that two production lots scheduled for release in January and February 1985 would not be available. Contacts with state health departments were immediately undertaken and it was determined that there were approximately 1.5 million doses on hand in the states.” Mason then resorted to understatement: “Comparing this amount to an average national monthly use ... indicates that vaccine supplies would be essentially exhausted before the end of February 1985.” In three months, the United States would run out of pertussis vaccine. Mason knew what was at stake; he had to do something to extend the supply. So he recommended a suboptimal vaccine schedule, figuring that some immunity was better than no immunity: “[We have] developed recommendations to try to ensure maximum prevention during the period of likely shortage. These involved delaying administration of the fourth dose of DTP, usually given at eighteen months of age, and the fifth dose, usually given at four to six years of age.”
On February 12, 1985, a few months after the CDC had recommended withholding the fourth and fifth doses of DTP vaccine, the American Academy of Pediatrics held an emergency meeting to discuss vaccine shortages. Representatives from the American Medical Association, the American Academy of Family Physicians, the Department of Defense, the Department of Health and Human Services, pharmaceutical companies, and state, county, and city health departments attended. The news wasn’t good. A survey of hundreds of physicians found that although most had followed the CDC recommendation, one in three still couldn’t find enough vaccine.
It got worse.
In 1979, three-month-old Kevin Toner became permanently paralyzed from the waist down after receiving DTP. Kevin suffered an uncommon disorder called transverse myelitis, in which one segment of the spinal cord becomes inflamed. There was then and remains now no evidence that either pertussis or pertussis vaccine causes transverse myelitis. But in a courtroom, that didn’t matter. The jury awarded Kevin $1.13 million. The company that was sued was Lederle Laboratories—the only American company still distributing pertussis vaccine. To Lederle, the message was clear. It wasn’t only children with epilepsy and mental retardation who could be compensated. Everything was on the table. Lederle knew that its vaccine prevented only whooping cough, tetanus, and diphtheria, not every other illness that occurred in the first year of life. The Toner case was the last straw. On April 1, 1986, Lederle Laboratories announced to the AAP and the Department of Health and Human Services that it would no longer produce and distribute DTP vaccine.
Other vaccines suffered. The number of companies making measles vaccine dropped from six to one and those making polio vaccine from three to one. Vaccine makers were getting out of the business. The United States was on the verge of returning to the pre-vaccine era.
Realizing that American children might soon be denied lifesaving vaccines, the federal government stepped in. On October 18, 1986, the last day of the Ninety-Ninth Congress, legislators passed a bill that protected vaccine makers: the National Childhood Vaccine Injury Act. One month later, President Ronald Reagan signed it into law. The act contained the Vaccine Injury Compensation Program (VICP), which included a list of compensable injuries possibly caused by vaccines. Designed to make things easier for parents, the act specified awards for loss of earnings, lawyers’ fees, and up to $250,000 for pain and suffering. At the center of the program stood the injury that had led to the act’s passage: seizures and brain damage allegedly caused by pertussis vaccine.
The purpose of the National Childhood Vaccine Injury Act was to allow children to be compensated for vaccine damages without having to go through the expensive process of suing in state courts; to protect pharmaceutical companies from litigation; and to encourage vaccine makers to continue to research and produce new vaccines. The government had taken the burden of litigation off the backs of vaccine makers and put it on its own.
Although legislators had designed the program to satisfy everyone, no one was satisfied. Edward Brandt, from the Department of Health and Human Services, said, “The bill establishes a strong presumption that vaccine is responsible for essentially any adverse condition that happens after immunization unless there is incontrovertible evidence of other causation. This presumption of guilt would undermine public confidence in immunizations.” The American Medical Association wanted a panel of scientific experts to determine which vaccine side effects would be compensated, concerned that the task would otherwise fall to members of Congress. And parents were worried that vaccine makers, now largely protected from litigation, would have little interest in making vaccines safer. Henry Waxman, the California Democrat who had sponsored the legislation in the House of Representatives, said, “I recognize the bill I have introduced is probably not the first choice of most parties to this controversy. Manufacturers would undoubtedly prefer greater insulation from liability. Parents of injured children would certainly prefer larger compensation and fewer restrictions on court activity. The Reagan administration would, I am sure, prefer legislation that spends no money.”
Henry Waxman proposed legislation that saved vaccines for American children. (Courtesy of Bloomberg via Getty Images.)
Despite everyone’s misgivings, the National Childhood Vaccine Injury Act saved vaccines. In 1986, the year of the bill’s passage, lawyers filed 255 lawsuits against DTP-vaccine makers; by 1996, ten years after the act was passed, they filed only six. Also, the act provided a mechanism to inform parents about vaccine safety, a system to independently review vaccines, and the means to report suspected side effects through the Vaccine Adverse Events Reporting System, or VAERS.
In May 1982, Kathi Williams and Dissatisfied Parents Together had stood before Paula Hawkins’s congressional committee and read a list of demands. Only four years later, they’d gotten much of what they’d wanted.
Like their counterparts in the United States, British health officials would also be forced to confront lawsuits, angry parent groups, and distrustful media. But unlike what had happened in the United States, where vaccines were almost eliminated, the outcome in England would be different. The controversy would lead to one of the most unusual and dramatic product liability cases in modern history, and end with a surprising answer to the question of whether pertussis vaccine had caused permanent harm at all.
CHAPTER 3
A Crude Brew
Nothing in life is to be feared—only to be understood.
—MARIE CURIE
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 194
8, 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.
Deadly Choices: How the Anti-Vaccine Movement Threatens Us All Page 4
