The next day, nineteen hours after the attack, Billy was back at the hospital as instructed. He was injected with another dose of duck-embryo vaccine. Doctors also injected Billy’s wounds, and his buttocks, with antirabies antibodies from horses. This is called “passive immunization” and gives victims ready-made immunity to protect them until their own immune responses, prodded by vaccination, kick into full gear. Passive antibody injections are a crucial part of postbite rabies treatment to this day. (In rich countries human antirabies antibodies have replaced those from horses, which frequently provoke allergic reactions.)
Two days after the attack the dog’s brain was examined at the Institut Pasteur in Casablanca. Looking at the canine brain cells under the microscope, pathologists found them scattered with deeply purple-staining, circular densities. They were called Negri bodies. They were full of virus, and they are the microscopic hallmark of rabies.
For twelve more consecutive days, Billy returned to the hospital and was injected with duck-embryo vaccine. Ten and twenty days after these injections were completed, he received booster shots. Then, in mid-June, he resumed the life of an eight-year-old boy.
• • •
RABIES THREAT WORSENS ran a headline in the Kingsport Times-News, published in a town in the mountains of northeastern Tennessee, on May 9, 1964, one day after Billy was bitten in Morocco. “Rabies among the grey fox population of Hawkins County is getting worse, with nine confirmed cases being found among the critters during the past month,” the article began.
“The situation is getting so bad here that a health department official is advising persons walking in hilly or wooded areas to carry clubs to defend themselves with.”28
One man reported that a gray fox had come out of hiding underneath his front porch and tried to attack him. The animal escaped after a fight with the man’s three dogs. They were unvaccinated and had to be put down.29
In Greene County, directly south of Kingsport, some 1,100 unleashed dogs would be shot and more than one hundred people bitten by rabid foxes in the coming months. Farmers carried shotguns. When the days shortened later that year, schools began to open late, so that children would not have to wait for buses before daybreak.30
In 1964 cases of animal rabies in the United States jumped by 20 percent to nearly 4,800. The increase was driven by wild animals. While rabies in domestic dogs and cats was falling steadily as more people vaccinated their pets, that decline was more than offset by rabid skunks and foxes in particular, along with other wild animals. Wild creatures accounted for 4,155, or 86 percent, of the animal cases that year.31 Some scientists speculated that a decline in the hunting of animals for pelts had caused their populations to boom and provided a large reservoir for rabies.32
In Mississippi, where no animal rabies had been reported in the prior two years, fifty-seven residents were bitten by rabid bats—which were also identified in forty-three other states. In southern Georgia, where no cases had been reported for seventeen of the previous eighteen years, 107 rabid raccoons were identified. Northeastern states including Maine, New Hampshire, and Connecticut saw their first significant increases in animal rabies in two decades.33 “Frankly, we’re faced with a problem for which we see no solution,” James H. Steele, the chief of the veterinary section at the CDC, told the Wall Street Journal.34
In the same article Koprowski was quoted saying that he was developing an improved vaccine made in human cells and was tentatively preparing to test it in seventy “volunteer” inmates at the state prison in Vacaville, California. It appears that this trial never came to fruition, for there is no report of it in the medical literature.
• • •
On August 3, 1964, three months after his dog attacked him in Rabat, Billy became irritable. He complained of a sore throat and ran a low-grade fever. A doctor looked at his throat, saw that it was red, took a swab to see what bacteria might grow from it, and prescribed penicillin.
Over the next three days Billy became more testy. He withdrew. He lost his appetite. He reacted to changes of temperature with cries or muscle spasms. He became afraid of water and swallowed the penicillin pills without it. He complained that it hurt when he swallowed.
On the third day of these symptoms, his parents took him back to the hospital at the Naval Air Station, where he was admitted. He was alert, but he didn’t want to be touched. When a doctor tried to examine him, he withdrew forcefully.
Over the next two days Billy deteriorated. He refused to drink anything. He began salivating excessively. He wouldn’t swallow the extra saliva, so he drooled. Forty hours after he arrived at the hospital, he got on his hands and knees on his hospital bed. He told the nurses that this relieved the irritating feeling of the sheets on his skin. He began trying to bite his attendants and kept trying, even after being sedated. He bled into his digestive tract. He battled severe muscle spasms and struggled to breathe. Finally he had several uncontrollable seizures and died, forty-seven hours after arriving at the hospital and ninety days after his dog attacked him.
An autopsy was performed. The experts at the Institut Pasteur in Casablanca found no Negri bodies in Billy’s brain. (They are missing in at least 20 percent of rabies cases, and their absence doesn’t rule out the disease.) So they took his fresh brain tissue and injected the brain of a rabbit with it. Sixteen days later they sacrificed the rabbit and looked at its brain cells. There they found Negri bodies.
The doctors who later described Billy’s case in the Annals of Internal Medicine did not declare it an open-and-shut case of vaccine failure. Perhaps the vaccine had been potent when it was shipped from the United States to the Naval Air Station in Morocco but was damaged in transit. Perhaps nineteen hours had been too long to wait to inject the horse antibodies at the site of the wounds, and the virus was already making the relatively short journey from Billy’s facial nerves to his brain by then; some experts believed that, once in the nerves, the virus became inaccessible to attacking antibodies. Perhaps the horse antibodies had destroyed enough of the rabies virus in the duck embryo vaccine that Billy did not generate a powerful immune response of his own. Such interference with the vaccine by the horse antibodies had been shown to occur in humans, which is why at least fourteen injections of the vaccine and two booster doses were required. Perhaps Billy should have had more than fourteen injections, or his booster doses should have been spaced out further in time after the initial injections, keeping his immune system gunning. They would never know.35
• • •
While Billy was dying in Morocco, a ten-year-old boy named Gary Sprick was camping in a tent on his family’s farm in Wabasha County, Minnesota, with his sister and four-year-old nephew. On August 5, as he slept, a skunk came into the tent and bit him on his right wrist and on the pointer and pinkie fingers of his left hand. The skunk would not let go until Gary’s sister shone a flashlight at it. It escaped. The resulting bites, doctors would later note, “were not clean puncture wounds but appeared to be chewed.”36
Gary was injected with duck-embryo vaccine on the day that he was bitten and for thirteen more days running. It is not recorded whether he also received an injection of equine antirabies antibodies. On August 25, twenty days after the attack, Gary noticed that his right forearm was numb. He developed a fever and his muscles ached. He complained that his neck was stiff. Three days after his symptoms began, he was admitted to a hospital in Rochester with paralysis that was climbing up his body from his limbs. He was hallucinating, uncoordinated, and running a fever of 104 degrees Fahrenheit. He died on September 1.
One year later the CDC published an assessment of Gary Sprick’s death. It noted that the incubation period of his disease, the time from the bites to the first symptoms, had been, in the context of rabies, very brief—twenty days. “As experience has shown that rabies vaccine is usually effective in preventing rabies only when . . . the incubation period exceeds thirty days,” they conclude
d, “this is not considered to be a case of vaccine failure.”37 The circularity of that reasoning apparently didn’t faze the authors.
The agency’s opinion had changed by 1966, when it published a similar report involving another ten-year-old boy; another backyard tent, this one in South Dakota; another rabid skunk; another timely series of twenty-one duck-embryo vaccine injections; and another agonizing, protracted death.
The South Dakota boy’s demise, the CDC authors wrote, showed the current therapies’ stark limitations. “In spite of nearly ideal management including thorough cleansing of the wounds, [injection of the wound with antirabies antibodies from horses], and a full course of vaccine, the patient developed rabies in less than 30 days from the time of the bite.”38
In 1964, the year that rabies in wild animals surged to the highest level in at least a generation, roughly thirty thousand people in the United States were vaccinated after encounters with potentially rabid animals; the CDC would later estimate that only one hundred to two hundred of the animals were actually rabid.39 Among the bite victims Gary Sprick was the only person to die. In 1965 just one American died after being bitten by a rabid dog: a sixty-year-old West Virginia woodsman who had also received a prompt fourteen-dose course of vaccine.40 The boy in South Dakota, who also promptly received the duck-embryo vaccine, was the only person to die of rabies in the United States in 1966. Clearly the duck-embryo vaccine worked in many cases. But for several heartbroken families, it didn’t work often enough.
In September 1964, the month that Gary Sprick died, Koprowski, Wiktor, and Fernandes published for wider circulation, in the Journal of Immunology, the exciting findings that Koprowski had presented one year earlier at the symposium in Opatija, Croatia, showing that they had developed a rabies vaccine using WI-38 cells, and that it successfully immunized mice.41 By that time they had tested the new vaccine in a species much closer to humans: fifty rhesus monkeys at the National Center for Primate Biology at the University of California at Davis.42 The results were encouraging. All of the animals promptly developed antirabies antibodies, and the levels of those antibodies peaked at fourteen days after vaccination. After this they declined just slightly, then remained consistently high compared to control animals for the three months that Koprowski’s team followed them before publishing the paper.43 Of course, the vaccine hadn’t yet passed the only test that mattered: protecting the animals when they were injected with real-world, disease-causing rabies virus.
That September Koprowski also filed with the U.S. Patent and Trademark Office an application for a patent on a “method of producing rabies vaccine.”44 It named him, Wiktor, and Fernandes as the inventors of a new vaccine that was both more effective and safer, by virtue of being grown on the human fetal cells that Hayflick had provided.
Because a grant from the NIH’s National Institute of Allergy and Infectious Diseases had supported the trio’s work to develop the improved rabies vaccine, the Wistar Institute would normally have been prevented from applying for a patent: in this era the U.S. government claimed ownership of all inventions discovered using its funding. However, the government did grant waivers on a case-by-case basis, if U.S. officials could be convinced that allowing an institution like the Wistar to patent an invention and then license it to a company was the only way to speed it to market for the public good. In the case of the potentially much-improved rabies vaccine, the United States granted a waiver, allowing the Wistar to become the owner if its application was successful.45
A patent would give the Wistar the exclusive right to make and sell the new vaccine for seventeen years going forward. Of course, the Wistar wasn’t a vaccine company. But a patent would also give the institute the right to negotiate licenses with companies to make and sell the new vaccine—in exchange, they would have to pay royalties to the institute. And as director Koprowski would have the power to steer a portion of those royalties to the personal pockets of the inventors: himself, Wiktor, and Fernandes.
Hayflick was not named on the rabies vaccine patent application. In fact, he was completely unaware of it.
CHAPTER TWELVE
Orphans and Ordinary People
Philadelphia, 1964–65
Toms River, New Jersey, 1964–68
The principle of medical and surgical mortality, therefore, consists in never performing on man an experiment which might be harmful to him to any extent, even though the result might be highly advantageous to science, i.e., to the health of others.
—Claude Bernard, French physiologist, 18651
The St. Vincent’s Home for Children, at 6900 Greenway Avenue in southwest Philadelphia, was made of red brick, stood three stories tall, and took up most of a city block. Its two symmetrical wings were marked by long rows of rectangular windows. Broad steps led from the sidewalk to two sets of swinging front doors. The pediments high above these were crowned with stone crosses, for the Roman Catholic Archdiocese of Philadelphia owned and operated the home, where the cornerstone had been laid in 1937.
While many called the St. Vincent’s Home an orphanage, not all the parents of the sixty-five children who lived there in November of 1964 were dead.2 Some were sick, or destitute, or in jail, or heading that way. Or they were unmarried girls and young women who had chosen, or been forced, to give up their babies.3 Many of those young mothers gave birth at the home and hospital for unwed mothers across the lane, where more than four hundred babies would be born in 1965.4 Those babies born at St. Vincent’s Hospital for Women and Children who weren’t adopted or placed with foster families by the time they turned one year old—often black or mixed-race infants who were difficult to place for adoption—were transferred the fifty yards to the Home for Children.5
Five nuns staffed St. Vincent’s Home, helped by a corps of hired child-care workers who dressed and fed the toddlers, changed diapers, played with the children, and bathed them each evening, assembly-line fashion. There were also two cooks, two adopted stray dogs named Jamie and Steve, and a grumpy maintenance man named Mr. Messina.6
The nuns belonged to the Missionary Sisters of the Precious Blood and wore friendly if impractical white habits up whose wide sleeves more than one stream of pee found its way during diaper changing. They lived in simple single rooms on the third floor and worshipped in a small chapel on the ground floor.
The rest of the lower two floors housed the children. It was a Spartan place, with hard terrazzo floors and stall-less bathrooms with tiny toilets. The nuns tried to make up in love what the building lacked in physical warmth, making sure the kids got out every day on the small playground surrounded by chain-link fence, reading to them at story time, and walking them to nearby Cobbs Creek Park. Sister Agape, the administrator, was a fierce advocate for the children. She arranged a week at a beach house in the summer and used the fact of occasional visits by state inspectors to squeeze every penny she could out of the archdiocese for things like new bedspreads that might brighten the place. She was known for not countenancing staffers who were only there to collect a paycheck.
Still, the nuns worried about the children. Sister Damiane, a petite, Austrian-born nun in her late twenties, mused that they were children, after all, and there were so many of them. Every one of them needed one or two adults to belong to—a level of attention she couldn’t possibly provide.
There were crushing moments: The day that a foster family arrived to take one boy away and he unraveled in a cacophony of desperate screams and wails. The unforgettable, lost look that a nun named Sister Mary Joseph observed on the face of the deaf girl, E., when she discovered that the beautifully wrapped present that Archbishop John Joseph Krol handed to her at the annual Christmas party at a downtown hotel was in fact just a decoration—an empty box.7
It was from the bald, bespectacled Archbishop Krol, who had succeeded John Cardinal O’Hara in 1961 as Philadelphia’s top prelate, that Stanley Plotkin got a green light to study his new RA 27/3 rubella vi
rus in the children living at St. Vincent’s Home.8
In his letter requesting Krol’s permission, Plotkin did not explain to the archbishop that he had captured the vaccine virus from one aborted fetus and grown it in cells from another. Krol was passionately antiabortion. In 1973 he would call the Supreme Court’s Roe v. Wade decision striking down state criminal abortion laws “an unspeakable tragedy for this nation that sets in motion developments which are terrifying to contemplate.”9
In 1964 the archbishop gave the rubella study the go-ahead.
“The subjects were 31 healthy, normal children, aged 14 to 29 months (average, 21 months), from an orphanage supervised by the Archdiocese of Philadelphia,” Plotkin would write in the paper that resulted. “Permission to include the children in this study was obtained from parents or guardians.”10
As for U.S. government clearance, Plotkin was uncertain whether he even needed it. Products that were clearly vaccines did need formal approval to be tested in humans, from Roderick Murray’s DBS, in the form of a piece of paper called an “Investigational Exemption for a New Drug.” To win this approval, a product must have passed muster in lab and animal tests specified by the DBS.
In May 1964 Plotkin wrote to the DBS, calling RA 27/3 “non-vaccine material” that he intended for a trial “with the object of producing experimental rubella.” Would he need clearance from the DBS to run the trial, he asked? And if so, what safety tests would the division require in order for RA 27/3 to win that clearance? Could he receive a quick response? “We are anxious to begin tests with this material as soon as possible.”11
The Vaccine Race Page 23