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By the early 1970s Austrian, now a professor at the University of Pennsylvania, decided to resurrect Colin MacLeod’s pneumococcal vaccine. “I was told [by university administrators] that I could do anything that I wanted as long as I paid for it,” he recalled. Austrian found that thirteen different types of pneumococcus accounted for a large percentage of the disease. So with support from the NIH, he made a vaccine containing polysaccharides from each of those types. Austrian and the NIH then convinced the pharmaceutical giant Eli Lilly to make thousands of doses of his vaccine. Confident that he could now protect people against pneumococcus, he called the medical directors of three of South Africa’s largest gold mining companies and, on September 6, 1970, flew with his wife to Johannesburg to begin talks with them. That same day, members of the Popular Front for the Liberation of Palestine hijacked four planes bound for New York. “When we got off the plane we got an effusive welcome and we couldn’t figure out why,” recalled Austrian. “We were flying over North Africa when the planes were hijacked.”
Two years later, Austrian began the first test of his vaccine at the East Rand Preparatory Mine in Boksburg, fifteen miles east of Johannesburg. First established in 1893, the mine was one of the oldest and deepest in the country. Although sixty years had passed since Almroth Wright had tested his vaccine, conditions in the mines weren’t much better. Austrian decided to enroll men coming to work for the first time, reasoning that they were most likely to encounter types of pneumococci not found in their isolated rural communities. “It was an unforgettable experience,” recalled Austrian, “to descend to the deepest workings of the mine two miles below the earth’s surface and a mile below sea level.” Rock temperatures reached 125 degrees.
Austrian wanted to inject some miners with his pneumococcal vaccine and some with placebo. But to convince gold mine executives to use his vaccine, he had to throw in another vaccine: one against meninogococcus, a different bacterium that caused rapid, overwhelming infection. Meningococcus scared mining company officials. Workers would be fine one minute and dead four hours later. “Death gave gold mining a bad name,” recalled Austrian. “Money spent taking care of miners with pneumococcal pneumonia was just factored into the cost of the gold. But death from meningococcus was bad publicity. They let us do the [pneumococcal] study because of meningococcus.” One third of the miners received pneumococcal vaccine, one third received meningococcal vaccine, and one third received placebo. (Like the pneumococcal vaccine, the meningococcal vaccine was made from the polysaccharide coat of the bacterium.) Although he wanted to see if his vaccine saved lives, Austrian also wanted to know what levels of antibodies in blood correlated with protection against disease. This meant that he needed to collect blood samples before and after vaccination. Austrian’s intellectual interest angered officials from the mining company. “We wanted to study the serological responses to the vaccine,” recalled Austrian. “The [company authorities] were willing to [allow miners to] give blood when they were acutely ill, but they objected to having their blood drawn after they’d recovered. At one point I got a call from [the authorities] that they were going to call off the trial because it was interfering with the workforce of the mine. So I got on a plane on very short notice and went back to Johannesburg, where I met with the head of one of the mining companies. I pointed out to him that the vaccine had already saved him perhaps $100,000 in terms of medical expenses.” To this, the mine owner slowly shook his head, realizing for the first time just how little Austrian knew about his business. “He looked at me, and he said that this [was] a $3 million annual operation. He wasn’t interested in my problem. He had the coldest blue eyes I ever saw.” The mining executive eventually decided to let the trial continue on the condition that Austrian abandon his interest in testing blood from the miners.
Robert Austrian (center), winner of the 1978 Lasker Award, watches Dr. Michael DeBakey inoculate Mrs. William McCormick Blair, Vice President of the Lasker Foundation, with his pneumococcal vaccine, November 20, 1978.
When the experiment was over, Austrian found that his pneumococcal vaccine worked, reducing the incidence of disease by 80 percent. Elated, he went back to the United States, certain that Eli Lilly would mass-produce the vaccine. But Lilly, which previously had been one of the largest vaccine makers in the United States, had decided to leave the vaccine business. With a vaccine in hand that could save thousands of lives, Austrian faced the very real possibility that no company would make it. In the end, only Maurice Hilleman considered Austrian’s plea. “Dr. Hilleman on his own decided that Merck would make a vaccine,” recalled Austrian. “If Maurice had said ‘No,’ it would have all gone down the drain. I don’t know of anybody else in the vaccine business who was ready to step up if Maurice hadn’t supported this.”
In 1977 Maurice Hilleman and Merck made the first pneumococcal vaccine, designed to prevent infection with fourteen different types of pneumococci. In 1983 they made a second pneumococcal vaccine, containing even more different types. Austrian considers the pneumococcal vaccine to be one of the most unusual vaccines ever made. “This is probably the most complex vaccine that we have,” says Austrian. “It’s designed to protect against twenty-three different infections.”
The CDC now recommends Robert Austrian’s pneumococcal vaccine for people more than sixty-five years old, those most likely to die of the disease. Unfortunately, many elderly adults in the United States don’t get the pneumococcal vaccine, probably our most underutilized weapon in the fight against serious, and occasionally fatal, pneumonia. Worldwide, about two million million people die of pneumococcal infections every year.
IN ADDITION TO BEING AMONG THE FIRST TO MAKE A VACCINE AGAINST pneumococcus and later meningococcus, Hilleman and Merck were also among the first to make a vaccine against a bacterium called Haemophilus influenzae type b (Hib). Unlike pneumococcus, Hib, which causes severe meningitis, bloodstream infections, and pneumonia, preferentially kills young children. Unfortunately, researchers soon found that Austrian’s idea of using bacterial polysaccharides to protect against diseases caused by bacteria like pneumococcus, meningococcus, and Hib didn’t work in infants, who simply couldn’t mount an immune response to bacterial polysaccharides. If Hilleman and others were going to protect young children against these bacteria, they were going to have to find a different way to do it.
In the late 1970s, John Robbins and Rachel Schneerson at the NIH and David Smith and Porter Anderson at Rochester University found that when they linked Hib polysaccharide to a protein, they could induce Hib antibodies in infants. The work inspired Merck and other companies to make a Hib vaccine. By the end of the twentieth century the incidence of Hib infections in young children had decreased by 99 percent.
The development of bacterial vaccines came just in time. The widespread use of a variety of different antibiotics has caused many bacteria, including pneumococcus, to become resistant to them. Unfortunately, pharmaceutical companies no longer devote much energy to making antibiotics. Vaccines may eventually stand alone as our last chance to fight bacterial infections.
MAURICE HILLEMAN PERFORMED EXPERIMENTS CRITICAL TO THE DEVELOPMENT of the measles, mumps, rubella, hepatitis A, and hepatitis B vaccines, saving millions of lives every year. He was also the first to develop and mass-produce the pneumococcal and chickenpox vaccines and among the first to make the meningococcal and Hib vaccines. But from the 1990s into the twenty-first century, Maurice Hilleman, his vaccines, and his science would be at the center of a storm of controversy. Joe Lieberman, John Kerry, Dave Weldon, Dan Burton, Don Imus, Tim Russert, Robert Kennedy Jr., Doug Flutie, Anthony Edwards, and Cindy Crawford were among hundreds of politicians, sports figures, media personalities, and actors who stepped forward to oppose much of what Hilleman had accomplished.
CHAPTER 10
An Uncertain Future
“To hear the allegation is to believe it. No motive for the perpetrator is necessary, no logic or rationale is required. Only a label is required. The lab
el is the motive. The label is the evidence. The label is the logic.”
PHILIP ROTH, THE HUMAN STAIN
Vaccines face an uncertain future. On one hand, we can now make vaccines that are safer and better than ever before. In June 2006 vaccine makers licensed a vaccine to prevent infection with human papillomavirus (HPV), which causes cervical cancer, one of the most common cancers in the world. Cervical cancer kills about three hundred thousand women every year. After identifying which HPV protein evoked protective immunity, researchers took the gene that made the protein, put it into a plasmid, and put the plasmid inside common baker’s yeast (the same strategy that was used to make Hilleman’s hepatitis B vaccine). The yeast proceeded to make large quantities of the HPV protein. Then something fairly amazing happened: HPV proteins reassembled into a whole virus particle. Through an electron microscope, synthetic HPV was indistinguishable from natural HPV. The only difference between the two was that the synthetic virus didn’t contain any viral DNA, so it couldn’t possibly reproduce or cause disease. When this synthetic virus was given to thousands of women, it prevented HPV infection. The HPV vaccine was our second cancer vaccine (hepatitis B vaccine was the first).
The twenty-first century also witnessed the birth of two other vaccines, which protected against pneumococcal and meningococcal infections in children. The FDA licensed these two vaccines—both made by linking the complex sugar (polysaccharide) that surrounds bacteria to a harmless protein—in 2000 and 2005, respectively. With a vaccine to prevent pneumococcal infection, the incidence of pneumonia and bloodstream infections in children declined 75 percent. With the availability of a meningococcal vaccine, parents finally had a weapon against one of the most frightening diseases of children and teenagers. Every year in the United States meningococcus causes about three thousand cases of rapid, overwhelming bloodstream infections and meningitis. No infection causes greater panic in elementary schools, high schools, or colleges.
In February 2006 vaccine makers licensed a vaccine against rotavirus, one of the greatest killers of infants and young children in the world. Rotavirus attacks the small intestine, causing fever, vomiting, and diarrhea. Because the vomiting can be frequent, persistent, and severe, it’s sometimes hard for children to recoup the fluids that they’ve lost. As a consequence, they can rapidly become dehydrated and die. In the United States alone, rotavirus causes one of every fifty infants to be hospitalized with severe dehydration. Worldwide, rotavirus kills six hundred thousand children every year—about two thousand every day. Scientists made the vaccine by capturing a strain of rotavirus that causes disease in cows but not people, purifying it, and combining it with human strains of rotavirus. Unlike the procedure with measles, mumps, rubella, and chickenpox vaccines, researchers first figured out which genes from human rotavirus made children sick and which genes caused a protective immune response. Now researchers no longer have to grow human viruses in animal cells and hope that they become weaker. They can simply figure out which genes make a virus dangerous and make sure that those genes aren’t in the final vaccine. “Everything before was empirical and scientifically modest,” says Adel Mahmoud, an Egyptian-born parasitologist and former president of the Merck Vaccine Division. “It was grow the bug, attenuate it, kill it, boil it, formalinize it, and it becomes a vaccine. The new vaccines launched at the beginning of this century are an order of magnitude above anything else that anybody would have dreamt of.”
There’s more good news. The gap in immunization rates between rich and poor countries is closing. In 1974, the WHO launched a program that increased immunization rates in the developing world from 5 percent to 40 percent. Perhaps the greatest success of the global immunization program has been the decline in the number of deaths resulting from measles—from eight million to less than half a million per year. Despite these successes, the WHO program has struggled to get vaccines to the children who need them. Of the one hundred thirty million children born every year in the world, between two million and three million still die of diseases preventable by vaccination. “We’re perfectly willing to give away vaccines to the developing world,” said one pharmaceutical company executive. “But we’d send vaccines to Africa and watch them fry on the tarmac.” At the turn of the century, two people stepped forward with a plan to change that.
In 2000 Bill and Melinda Gates gave about $1 billion to create the Global Alliance for Vaccines and Immunizations (GAVI), with the caveat that the money could not be used until it was matched, dollar for dollar. UNICEF, the WHO, the World Bank, vaccine makers, and governments from ten countries met the Gateses’ challenge. By December 2005, with more than $3 billion to spend, GAVI provided millions of doses of the hepatitis B, diphtheria-tetanus-pertussis, and Hib vaccines to the poorest countries. Immunization rates rose dramatically. “I’m a lot more optimistic than two decades back,” says Mahmoud. “Investing in health is investing in the future. Not only does wealth make health, but health makes wealth.”
We are now on the brink of successfully bringing vaccines to the developing world and closing a gap that has existed for centuries. We are, in many ways, at the dawn of a new age of vaccines. Unfortunately, during the past twenty years, forces designed to crush vaccines may have gained the upper hand.
TOWARD THE END OF HIS LIFE MAURICE HILLEMAN FOUND HIMSELF in the middle of several controversies. The most enduring, mean-spirited, and sensational charge against him was that his vaccines, despite all of their success, caused autism.
Autism is an enigmatic disorder with a heartbreaking array of symptoms. Children with autism struggle to communicate with their parents, siblings, and classmates. They are often withdrawn; engage in repetitive, self-stimulating behaviors; eat poorly; and seem to live in a world of their own. Few things are more difficult for a parent then watching a child struggle to communicate. Autism became widely known in the early 1980s thanks to the television series St. Elsewhere, which depicted the lives and work of the staff of a fictional hospital, St. Eligius. The son of one of the main characters was severely autistic. During the final episode, the boy slowly turns over a snow globe containing a replica of the hospital, the years-long drama apparently a product of his wondrous imagination.
By the late 1960s Hilleman had decided to combine his measles, mumps, and rubella vaccines into a single shot, later known as MMR. He thought that getting one shot would be better than getting three. “It came out of a vision,” said Hilleman, “a long-term dream that it might be possible one day to protect against these diseases in a single shot.” Merck released Hilleman’s MMR vaccine in the United States in 1971 and in the United Kingdom in 1988. Ten years later, a British researcher claimed that Hilleman’s MMR vaccine had caused an epidemic of autism.
In February 1998 the prestigious Royal Free Hospital in London held a press conference. Journalists crowded into the meeting room, anxious to hear the results of a study soon to be published in the Lancet, a highly respected, widely read British medical journal. Sitting on a dais under the heat of television lights were five doctors, including the dean of the medical school. In the center of the group was the lead author of the study, Dr. Andrew Wakefield.
Wakefield was a compelling figure. Described by journalists as “tall, handsome, fluent, and charismatic [with] a sense of humor, a cultured British accent, and the body of a rugby player,” Wakefield told the audience about eight British children in whom autism and intestinal problems had developed soon after they received the MMR vaccine. Wakefield reasoned that the measles vaccine contained in MMR, although injected into the arm, had damaged the intestinal lining, causing children to suffer abdominal pain and diarrhea. Because the intestinal surface no longer provided an adequate barrier, harmful proteins could enter the bloodstream and travel to the brain, where they caused autism. The study was full of holes. Wakefield didn’t say what these proteins were; he hadn’t identified them. He didn’t say how measles virus given in the arm was destroying the intestine. He didn’t say why measles vaccine would be more h
armful when contained in MMR than when given alone. And, most important, Wakefield hadn’t compared the incidence of autism in children who had received the MMR vaccine with those who hadn’t. He only had a theory. But if he was right, autism now had a villain: Maurice Hilleman, the man who had decided to combine the three vaccines into one.
Parents of children with autism were intrigued by Wakefield’s finding. Their children had been healthy, then received the MMR vaccine, then became autistic. Was this a coincidence? Or was the MMR vaccine really causing autism? Because about 90 percent of children in the United Kingdom had received the MMR vaccine soon after their first birthday, and because symptoms of autism typically appear when a child is between one and two years of age, it wasn’t surprising that Wakefield found several children who had become autistic within one month of receiving the MMR vaccine. But anecdotal associations, which can be very powerful, can also be misleading. “We evolved to be skilled, pattern-seeking, causal-finding creatures,” says Michael Shermer in Why People Believe Weird Things. “Those who are best at finding patterns—[for example] standing upwind of game animals is bad for the hunt; [or] cow manure is good for the crops—left behind the most offspring. We are their descendents. The problem in seeking and finding patterns is in knowing which ones are meaningful and which ones are not. Unfortunately our brains are not always good at determining the difference.” One example of the power of anecdote can be found in the story told by a Philadelphia-area nurse practitioner. “A mother of a four-month-old brought her baby into the office for her shots,” she recalls. “The baby was sitting on the mother’s lap while I was drawing one of the vaccines into a syringe. I looked over and the baby started to seize. There was a history of seizures in the family, and the child went on to become epileptic. But imagine what the mother would have thought if I had given that vaccine five minutes earlier. She would have been convinced that the vaccine had caused her daughter’s epilepsy. And all of the statistical data in the world showing her that it didn’t wouldn’t have convinced her otherwise.”