Vaccinated (4 page)

In addition to abuse and neglect, the overcrowding, poor sanitation, and inadequate staff at Willowbrook led to the spread of many infectious diseases, including measles, influenza, and shigellosis, and those caused by intestinal parasites. But no infection was more damaging than hepatitis. In an effort to control outbreaks of hepatitis, the medical staff at Willowbrook consulted Saul Krugman, an infectious disease specialist at Bellevue Hospital in New York City. Krugman found that hepatitis developed in 90 percent of children admitted to Willowbrook soon after their arrival. Although it was known that hepatitis was caused by a virus, it wasn't known how hepatitis virus spread, whether it could be prevented, or how many different types of viruses caused the disease. Krugman used the children of Willowbrook to answer those questions. One of his studies involved feeding live hepatitis virus to sixty healthy children. Krugman watched as their skin and eyes turned yellow and their livers grew bigger. He watched them vomit and refuse to eat. All the children fed hepatitis virus became ill, some severely. Krugman reasoned that it was justifiable to inoculate retarded children at Willowbrook with hepatitis virus because most of them would get hepatitis anyway. But by purposefully giving the children hepatitis, Krugman increased that chance to 100 percent. “They were the most unethical medical experiments ever performed in children in the United States,” said Hilleman. Art Caplan, director of the Center for Bioethics at the University of Pennsylvania, agrees. “The Willowbrook studies were a turning point in how we thought about medical experiments in retarded children,” said Caplan. “Children inoculated with hepatitis virus had no chance to benefit from the procedure—only the chance to be harmed.”

Caplan believes that the studies at Willowbrook weren't the only reason for the change in public sentiment about experiments on retarded children. In the early 1950s, scientists at the Massachusetts Institute of Technology (MIT) were interested in determining how people absorbed iron, calcium, and other minerals from food. The scientists went to the Walter E. Fernald School, an institution for disabled and retarded children in Waltham, Massachusetts, about twelve miles outside of Boston. Conditions at Fernald weren't nearly as barbaric as those in Willowbrook. Unlike Willowbrook, the Fernald School had a science club for teenagers. Members of this club would eventually participate in an experiment that put an end to studies on retarded children.

Funded by the National Institutes of Health (NIH), the Atomic Energy Commission, and the Quaker Oats Company, MIT researchers fed children breakfast foods tagged with small amounts of radioactive cobalt. They wanted to determine whether minerals contained in Quaker Oats products would move through the body in a manner different from, and presumably better than, minerals in other breakfast foods. Although the amount of radiation exposure was small—about three hundred millirems, less than the yearly radiation exposure of someone living at high altitudes, such as that of Denver—children given the radioactive food had no chance of benefiting from the experiment.

Today, because of the studies at Willowbrook and Fernald, medical researchers don't include retarded children in studies from which they cannot benefit. They also don't include them in studies from which they might benefit.

 

O
N
J
UNE
28, 1965,
ABOUT TWO YEARS AFTER
J
ERYL
L
YNN
H
ILLEMAN
had walked into her father's bedroom, Robert Weibel visited the Trendler School. Located in an old converted two-story house in Bristol, Pennsylvania, the school was home to thirty severely retarded children. Weibel injected sixteen of them with Hilleman's experimental mumps vaccine. (For Weibel the decision to inoculate retarded children had special significance. Weibel's son, Robert, had been born with Down syndrome in 1956.) Weibel found that Hilleman's vaccine was safe and that antibodies against mumps developed in vaccinated children. Encouraged, Weibel went to the Merna Owens and St. Joseph's Homes, both isolated in the countryside of northeast Pennsylvania. He found sixty severely retarded children who were susceptible to mumps, and on August 13, 1965, he injected half of them with Hilleman's vaccine. The results were the same. Children developed mumps antibodies but didn't get sick.

Hilleman, Weibel, and Stokes had shown that their vaccine induced mumps antibodies, but they hadn't proved that it prevented disease. To do that, they needed more children. For the next several months, Stokes and Weibel handed out fliers describing the new mumps vaccine to nursery schools and kindergartens in the Philadelphia area. If parents were interested, they could attend informational meetings to be held at local churches. “Parents were eager to join up,” said Weibel. “They trusted us, and we were straightforward with them. They knew that diseases like measles and mumps could be pretty bad, and they wanted to help out. In those days people were a little less focused on themselves and more focused on their community. They wanted to make a difference.”

Hilleman attended two of the meetings in the Philadelphia suburb of Havertown, but he didn't do any of the talking. “At the Sacred Heart Church Maurice wanted to remain inconspicuous,” recalled Weibel, “so he stood in the back. He was leaning up against the door frame when he accidentally backed into a vessel of holy water nailed to the wall. He drenched the back of his shirt and was quite shaken, apologizing endlessly to the priest. The priest reassured him by saying that there was plenty where that came from.” During another meeting, Hilleman remembered a parent asking how the vaccine was made. Joe Stokes answered the question. Handsome, with silver-gray hair and the gentle spirit of his Quaker background, Stokes told the story of a German man who had left his wedding ring on a nightstand. During the night a spider made a dense, intricate web by going back and forth, side to side. By the morning the web had covered the entire opening in the ring. “He was trying to explain what chick cells looked like when they grew in laboratory flasks,” recalled Hilleman. “He called it
Gewebekulter
—web culture. Jesus, they were spellbound.”

Parents interested in participating in the study received a three-by-five-inch card stating, “I allow my child to get a mumps vaccine.” At the bottom of the card was a line for the parents' signatures. Unlike the practice today, the consent card didn't contain an explanation of the disease, a description of the vaccine, a list of vaccine components, a discussion of previous studies, the need for blood tests, or a statement of possible risks and benefits. Parents were also given Robert Weibel's work and home telephone numbers. If they had any questions about the vaccine or if they were worried that the vaccine was causing a problem, they could call him at any time, day or night. Weibel, in turn, would drive to their homes and examine their children.

Stokes and Weibel recruited about four hundred children for their study; two hundred received Hilleman's vaccine, and two hundred received nothing. “Then we waited,” recalled Weibel. Several months later, a mumps epidemic swept through Philadelphia. Sixty-three children in the study came down with mumps. Two of the sixty-three had been vaccinated. Sixty-one of them had not been. Hilleman's vaccine worked, and it worked well. On March 30, 1967, four years after Jeryl Lynn Hilleman had come down with the mumps, the Jeryl Lynn strain of mumps vaccine was licensed. Since then, more than one hundred fifty million doses have been distributed in the United States. By 2000, mumps vaccine had prevented almost one million children from getting mumps every year and had prevented meningitis and deafness in thousands. Furthermore, the introduction of Hilleman's mumps vaccine in Denmark, Finland, Norway, Sweden, Slovenia, Croatia, England, Wales, Israel, Poland, Romania, and Latvia has virtually eliminated the disease from those countries.

Jeryl Lynn Hilleman is now the executive vice president and chief financial officer of Symyx, a research technology company in Santa Clara, California. “People ask me what it means to be Jeryl Lynn, the namesake of the vaccine. I tell them that it just made me very proud of my father. If being sick at the right time with the right virus helped—great.” One reporter later wrote, “Jeryl recovered from mumps virus, but mumps virus never recovered from infecting Jeryl.”

W
hat possessed Maurice Hilleman to take his daughter's mumps virus and inject it into hen's eggs and minced chick embryos? Why did he cut off the chicks' heads before using them? And most importantly, why in the 1960s did he resort to a process so seemingly crude, arcane, and convoluted? Eight critical experiments performed during the previous century determined Hilleman's choices.

 

F
ROM
E
DWARD
J
ENNER
, H
ILLEMAN LEARNED THE POWER OF VACCINES.
Jenner's vaccine eradicated humankind's deadliest infection, smallpox, from the face of the earth.

Easily spread by tiny droplets of saliva containing millions of virus particles, smallpox was a common, severe, debilitating infection. The virus caused high fever and a permanently disfiguring, pus-filled rash with a smell reminiscent of rotting flesh. Smallpox killed one of every three of its victims and blinded many survivors. In 1492, when Christopher Columbus crossed the Atlantic Ocean, seventy-two million Indians lived in North America; by 1800, only six hundred thousand remained. Smallpox—brought by European settlers—killed most of the rest. Indeed, smallpox has killed more people than all other infectious diseases combined.

In 1768, when Edward Jenner was thirteen years old and training as an apprentice apothecary in Chipping Sodbury, England, he approached a young milkmaid who appeared ill. “Are you coming down with the smallpox?” he asked. “I cannot take that disease,” she said, “for I have had the cowpox.” Cowpox was a disease that caused blisters on the udders of cows. Sometimes people who milked cows with cowpox would get these same blisters on their hands. Jenner was only a boy, so he didn't give much thought to the milkmaid's notion of what prevented diseases. But Edward Jenner remembered that conversation for the rest of his life.

Years later, while training in London, Jenner told the famous surgeon John Hunter about the milkmaid's observation. Hunter encouraged Jenner to test the theory. “Don't think, but try,” said Hunter. “Be patient, be accurate.” On May 14, 1796, several months before George Washington gave his farewell address, Edward Jenner got his chance. Sarah Nelmes, a milkmaid in Jenner's employ, had cowpox blisters on her hands and wrists. Jenner removed the pus from one of the blisters and injected it into the arm of James Phipps, the eight-year-old son of a local laborer. Six weeks later, Jenner injected Phipps with pus taken from a case of smallpox “in order to ascertain whether the boy, after feeling so slight an affection of the system from the cowpox virus, was secure from contagion of smallpox.” Typically, inoculation with smallpox caused high fever; chills; an ulcerating, painful rash; and occasionally death. But nothing happened to James Phipps. Later, Jenner injected Phipps twenty more times with pus from people with smallpox; each time Phipps survived without incident. Apparently, cowpox virus was similar enough to smallpox so that inoculation with one protected against disease caused by the other.

Two years later, Jenner published his observations under the lengthy title “An Inquiry into the Causes and Effects of Variolae Vaccinae, a Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire, and Known by the Name of Cow Pox.” Jenner used the term
variolae vaccinae
—literally “smallpox of the cow” and later the source of the word
vaccine
. Within one year of his publication, physicians had inoculated a thousand people with cowpox and had translated Jenner's observations into several languages. It took about two hundred years for Jenner's vaccine to eradicate smallpox from the face of the earth. (Although the disease is gone, the virus isn't. Fearing that smallpox virus—secretly preserved in scientific laboratories—would be used as a weapon of terror, the United States government supported a short-lived program to immunize hospital workers in October 2002, five months before the invasion of Iraq.)

Despite Jenner's success, scientific advances often come with a price—the landscape of vaccines is littered with tragedy. Jenner lacked a reliable, consistent, and continual source of cowpox virus. So he inoculated cowpox under the skin of a volunteer, waited eight days until it caused a blister, removed the pus, and inoculated it into the arm of the next person. Many children were vaccinated by this arm-to-arm technique. For example, in St. Petersburg, Russia, in 1801 a recently vaccinated girl was sent to a local orphanage to serve as a source of cowpox virus for other children. The orphanage continued arm-to-arm inoculation for more than ninety years. But arm-to-arm transfer of cowpox could be dangerous. One child inoculated by Jenner, a five-year-old boy named John Baker, was never challenged with smallpox. “The boy,” said Jenner, “was rendered unfit for inoculation [with smallpox] from having felt the effects of a contagious fever in a workhouse soon after this experiment was made.” Baker was unfit for inoculation because he had died of a bacterial infection, probably the result of a contaminated cowpox vaccine. In 1861 in Italy forty-one children got syphilis as a result of arm-to-arm transfer when a small amount of blood from one child in the chain, who had an undiagnosed case of the disease, was injected into others. And in 1883 in Bremen, Germany, arm-to-arm transfer caused a massive outbreak of hepatitis.

Although Edward Jenner made the first viral vaccine, he didn't know that smallpox and cowpox were related viruses. That was because he'd never heard of viruses. Edward Jenner made his observations several decades before scientists showed what viruses were and how they reproduced.

 

F
ROM
L
OUIS
P
ASTEUR, A
F
RENCH CHEMIST
, H
ILLEMAN LEARNED THAT
vaccines could be made from dangerous human viruses. (Jenner had used a cow virus.) Pasteur developed humankind's second vaccine, one that prevented a uniformly fatal disease: rabies.

On July 4, 1885, a rabid dog attacked a nine-year-old boy named Joseph Meister in the town of Meissengott, a small village in the province of Alsace, France. Meister, who was on his way to school, covered his face as the dog knocked him down and bit him fourteen times. A bricklayer walking nearby beat the dog with an iron bar and carried Meister home. The owner later killed the dog and cut open its stomach; out poured straw, hay, and fragments of wood—evidence that the animal had gone mad. (Old stories about infectious diseases often sound as if they had been written by the Brothers Grimm.)

In ancient times, people with rabies were hunted down like wild animals and strangled or suffocated. By the late 1800s, treatments for rabies had advanced to include the feeding of cock's brains, crayfish eyes, livers from mad dogs, snake skins mixed with wine, and poison from a viper, or the “dipping cure,” which involved holding victims under water until “they have done the kicking.” Techniques that actually worked to prevent rabies included immediately cauterizing a bite with a hot iron or sprinkling gunpowder on the wound and igniting it; these processes killed the virus.

Two days after the attack, Joseph Meister and his mother arrived at the front door of 45 rue d'Ulm in Paris, the home of Pasteur's laboratory. When Pasteur came to the door, Meister's mother dropped to her knees and begged him to save her son. Pasteur took the boy by the hand and gently guided him into his home, later describing the wounded child in his notebook, “Severely bitten on the middle finger of his right hand, on the thighs, and on the leg by the same rabid dog that tore his trousers, threw him down and would have devoured him if it had not been for the arrival of a mason armed with two iron bars who beat down the dog.”

For several years preceding Meister's visit to his laboratory, Pasteur had studied rabies virus. To make an experimental rabies vaccine, he found dogs that had died of rabies, ground up their spinal cords, injected infected spinal cords into rabbits, and watched the rabbits die of rabies. Then he removed the rabbits' spinal cords, cut them into thin strips, and dried them in airtight jars. Pasteur found that the longer he dried them, the longer it took for the infected spinal cords to cause disease. After fifteen days of drying, they didn't cause disease at all. Apparently, prolonged drying killed rabies virus. Pasteur then performed his groundbreaking experiment. He injected dogs with rabies-infected spinal cords that had been dried for fifteen days and then, successively, with spinal cords that had been dried for fewer and fewer days. At the end of the experiment, Pasteur injected dogs with spinal cords that contained live, deadly rabies virus. Typically, the dogs would have died of rabies. But all the dogs that received Pasteur's vaccine survived.

When Joseph Meister came to his laboratory, Pasteur had not yet immunized people, only animals. But at 8:00 p.m. on July 6, 1885, Meister was injected with a rabies-infected rabbit spinal cord that had been dried for fifteen days. Pasteur knew that such a spinal cord didn't kill dogs or rabbits. He could only hope that it wouldn't kill Meister. During the next eleven days, Meister was injected twelve more times with rabbit spinal cords that had each been less and less dried out and therefore were more and more likely to cause rabies. The final dose, on July 16, was taken from an infected rabbit spinal cord that had been dried for only one day—an injection that would have easily killed a rabbit. Pasteur knew that those final injections were potentially deadly. Writing to his children, he said, “this will be another bad night for your father. [I] cannot come to terms with the idea of applying a measure of last resort to this child. And yet [I have] to go through with it. The little fellow continues to feel very well.”

By the end of the month, Meister was home in Alsace, healthy. Using killed, partially killed, and live rabies virus, Pasteur had developed the first vaccine that protected people bitten by rabid animals from getting rabies. Parisians, who had to live every day in fear of rabid dogs prowling their streets, hailed Pasteur's vaccine as one of the greatest medical triumphs of the nineteenth century. But like Jenner's smallpox vaccine, Pasteur's rabies vaccine came with a price. As his vaccine was injected into more and more people, Pasteur found something that he hadn't anticipated: some people—as many as one of every two hundred who used it—became paralyzed and died. At first, Pasteur thought that people were dying of rabies. But they were dying of a reaction to his vaccine.

Today we understand the problem with Louis Pasteur's rabies vaccine. Cells from the brain and spinal cord contain a substance called myelin basic protein. This protein forms a sheath around nerves, like the rubber insulation that surrounds an electrical wire. Some people inoculated with myelin basic protein occasionally have an immune response against their own nervous systems: autoimmunity. Pasteur's vaccine, made from rabbit spinal cords that contained myelin basic protein, caused autoimmunity. (This was why Hilleman cut off the heads of chick embryos before using them. He didn't want to inject children with small amounts of myelin basic protein from the chicks' brains.)

Joseph Meister, who survived the bite of a rabid animal, lived to be sixty years old. When the Nazis occupying Paris in 1940 wanted to see the tomb of Louis Pasteur, Meister, then a guard at the Pasteur Institute, was the first to meet them. But the humiliation of opening his savior's tomb to the Nazi invaders was more than he could handle. Later, locking himself in his small apartment, Meister committed suicide.

 

F
ROM
M
ARTINUS
B
EIJERINCK, A PROFESSOR OF BACTERIOLOGY AT THE
Delft Polytechnic Institute in the Netherlands, Hilleman learned what viruses were, where they reproduced, and how they caused disease.

As Peter Radetsky describes in
The Invisible Invaders
, Beijerinck “would burst into his lab, a tall, striking figure in a dark coat and high collar. Around the rooms he would prowl, shutting all windows, disdainfully sniffing for the faintest remnant of cigarette smoke, and inspecting benches for as little as a drop of spilled water.” A mean-spirited, haughty, offensive man, Beijerinck often likened his students to untrained monkeys and refused to allow young associates to marry. His personality didn't limit his achievements, however. In 1898, Martinus Beijerinck performed an experiment that revolutionized microbiology.

Beijerinck was studying tobacco mosaic disease, which stunted the growth of tobacco plants and was common in Europe and Russia. Scientists had already seen bacteria under the microscope, shown that they caused specific diseases, and figured out a method to remove them from water: filtration through unglazed porcelain. (Pots of unglazed porcelain were often kept in the home to purify drinking water.) Beijerinck assumed that bacteria caused tobacco mosaic disease. To prove it, he squeezed diseased plants through a press, collected the sap, rubbed the sap onto healthy leaves, and watched the healthy plants die. Clearly, the sap contained the organism that caused the disease. Then Beijerinck performed his seminal experiment. He passed infectious sap through a porcelain filter and, much to his surprise, found that the sap still caused disease. Beijerinck knew that bacteria should have been trapped by the filter. Something else was getting through.

Beijerinck published his findings in a paper titled “Concerning a Contagium Vivum Fluidum as a Cause of the Spot-Disease of Tobacco Leaves.” The term
contagium vivum fluidum
translates as “living contagious fluid.” (Later, Beijerinck referred to the
contagium
as a virus.) Beijerinck said that “the contagium, in order to reproduce, must be incorporated into the living protoplasm of the cell.” Martinus Beijerinck had recognized the single most important difference between bacteria and viruses. Bacteria, capable of independent growth, can multiply on the surface of furniture, in dust, in rainwater, or on the lining of the skin, nose, or throat. But viruses, incapable of independent growth, can reproduce only within the “living protoplasm of the cell.” At the age of forty-seven, Martinus Beijerinck became the father of virology.