On February 1, 1965, Richard Stern, a tall, big-boned surgeon who despite his massive hands somehow performed microsurgery on infants, made a half-centimeter slit in one of ten-week-old Stephen’s eyes and inserted a tiny, spoonlike instrument, which he used to scoop out the liquefied, milky substance that composed the cataract. The next month he did the same thing to the other eye.
Cataract surgery on rubella-stricken infants in the 1960s had a dismal success rate and was fraught with postoperative complications that weren’t necessarily the surgeons’ fault.32 First, pediatric ophthalmology didn’t yet exist as a subspecialty. Surgeons like Stern were adult ophthalmologists trying to adapt their methods.33
Second, they were almost always dealing with undersized eyes.34 Rubella stunts the growth of the eyeball in the womb, just as it stunts other organs. That made the surgery technically tough.
What’s more, the operative techniques then available were primitive by today’s standards.35 Even such basics as operating microscopes were only just becoming available. (Stephen’s surgeon did have a microscope. That wasn’t a given. A nascent group of pediatric ophthalmologists in Washington, DC, were reduced to borrowing a microscope from their ear, nose, and throat colleagues.)36
Finally, in many cases the surgery itself stimulated a chronic, vicious cycle of inflammation that affected other parts of the eye, including the iris, the cornea, and the retina. Many infants and children ended up needing additional surgeries, and some in the end had to have their entire eye or eyes removed. It was a brutal, depressing business.37
So it was with great trepidation that several days after his first surgery Mary and Steve watched as the bandages were removed from Stephen’s eye. They had tied colored balloons on the rail of his hospital crib. Their baby brightened, waved his arms, and turned his head toward the balloons. He looked like he was trying to focus on something for the first time in his life.
The Wenzlers recall that when it came time for them to pay their bill, Stern charged them just $10 beyond what their insurer paid. “You are going to have enough challenges as it is,” he told them. They would consist, he said, not so much in getting Stephen used to the world as in getting the world used to Stephen.
Stern sent the Wenzlers to an expert who crafted a tiny pair of glasses with ultrathick plastic lenses and round frames of muted gold. Stephen began wearing them everywhere.
Mary recalls that, at some point when he was a child, Stephen’s sight measured 10/200 with his glasses on. This meant that he had to be ten feet away to perceive an object that a perfectly sighted person could see clearly at a distance of two hundred feet.
It was also during his first months of life that Mary began to suspect that Stephen couldn’t hear. He didn’t react when she came into a room. He didn’t look up when she clapped her hands or banged the lid of a pot. He didn’t turn his head at the sound of her voice. He reacted to her only when she touched his crib or touched him.
At a checkup with Dr. Pietrangelo, the Toms River family doctor who had delivered Stephen, Mary asked if her son might be deaf. Pietrangelo laid Stephen on his back on an examining table. He banged his hand, hard, on the table beside the baby. Stephen looked toward the noise.
There’s no problem with his hearing, Pietrangelo told Mary, handing him back to her. Later Pietrangelo called Steve Wenzler to tell him that he had found a heart murmur while listening to Stephen’s chest. The infant should be booked for a cardiac catheterization.
The Wenzlers did not go back to Pietrangelo. They asked Pica’s advice on where to take their son for heart care. That July cardiologists at Deborah Hospital in Browns Mills, a tiny town in the center of the state, inserted a catheter into a vessel in eight-month-old Stephen’s groin and snaked it up into his heart. Injecting dye, they saw the classic signs of a heart malformation that is common in congenital rubella. It was first flagged by Norman Gregg, the Australian physician who discovered congenital rubella syndrome; it was found in autopsies of three of his tiny patients and reported to him by other doctors.38
Patent ductus arteriosus (PDA) results when a fetal blood vessel—the ductus arteriosus, which links two major arteries leaving the heart—fails to close in the first few days of an infant’s life, as it should. (“Patent” means “open” in medical parlance.) In the fetus, which is not yet breathing on its own, the ductus allows blood to bypass a high-pressure circuit through the fluid-filled lungs. But in the newly born infant, now breathing for itself, an open ductus results in an aberrant circuit in which some of the freshly oxygenated blood that should be pumped out to the body, where it’s needed, instead is diverted to the lungs. The upshot is that the infant’s heart has to work extra hard to keep the body supplied with oxygenated blood. With time, and in severe cases that are not surgically repaired, the extra work can push the little heart into failure, with blood backing up into the lungs and slowly, in effect, drowning the child. Babies with PDA have symptoms like feeding poorly, shortness of breath, a racing heart, and poor growth.
The Wenzlers don’t remember that baby Stephen showed any of these signs. Mary does recall that he was slow to hit developmental milestones and that when he did so, he did so in his own way. He never crawled. Instead he lay on his back and propelled himself around the floor by pushing with his legs—possibly because this position allowed him to see better what little he could. Finally he started sitting up. And then, after his PDA was surgically repaired when he was not quite two years old, he began growing like a weed.
During his initial cardiac catheterization, the cardiologists also found that Stephen had multiple narrowings of branches of his pulmonary artery, the big vessel that carries blood from the right ventricle of the heart to the lungs for oxygenation. Along with PDA, this problem, called branch pulmonary artery stenosis, is the most common heart defect in children with congenital rubella.39 Severe branch pulmonary artery stenosis requires surgeons to insert a balloon catheter and sometimes a stent to clear the blockages. When this fails, a heart-lung transplant may be the only option. In Stephen’s case the narrowings did not cause symptoms, and the doctors adopted a wait-and-watch approach, as they still do today.
Just before Stephen’s first heart procedure, his parents’ life got even more complicated. Leonard, a brother for Stephen, was born in April 1966, when Stephen was seventeen months old. Mary was sick with worry during the pregnancy—irrationally, she told herself. But Leonard was born perfectly healthy.
The Wenzlers don’t remember, because the time was so busy and so chaotic and so traumatic, when it was that they got Stephen to a specialist who confirmed Mary’s suspicion that their son was profoundly deaf. What is clear is that Stephen was wearing hearing aids by the time he was three years old and that he heard, or perceived through vibrations, a very minimal degree of sound.
• • •
In September of 1968, when he was not quite four years old, Stephen Wenzler enrolled in the Beachwood Nursery School in Toms River. The preschool’s director, Mrs. D’Arienzo, had no special experience with disabled children, but she said she was willing to try including Stephen with her gaggle of able-bodied three-, four-, and five-year-olds.
Mrs. D’Arienzo soon came to like Stephen a lot. He was very bright, she told Mary, and just wanted to learn and do everything that the other kids did. In this Stephen was lucky; one third or more of children with congenital rubella are intellectually disabled, the virus having invaded their brains in the womb, damaging blood vessels, starving the brain of oxygen, and often stunting its growth. Nearly one in four children have abnormally small heads. In up to 7 percent of children with congenital rubella, the brain damage causes autism.40
Stephen didn’t fuss when Mary dropped him off for preschool—a good sign in a boy who didn’t hesitate to let his displeasure be known. He brought home drawings, which Mary posted on the refrigerator. Perhaps most important, Mrs. D’Arienzo taught Stephen discipline: that he needed to follo
w the rules of the school just like everybody else.
Photos of Stephen in this era show a grinning brown-haired boy wearing thick glasses with heavy black temples, his chin tilted up as he tries to focus through the lower half of his bifocal lenses. He is thin, and his blue gray eyes are magnified by the thick lenses. In his ears there are hearing aids bigger than quarters and ten times as thick. Cords hang down from them, leading to a receiver he wears strapped to his chest.
Mary Wenzler has kept many photos. Here is Stephen as a baby, chin dimpled and cheeks like porcelain, tiny glasses perched on his nose, a faraway look in his eyes that says he is not focusing on the camera. Here are photos of Stephen with his brother, Leonard, in a child’s wagon; here are the brothers riding on their dad’s back in the backyard; here they are ringing a big black bell at a firehouse. Here is Stephen, four years old, in a bed at the Children’s Hospital of Philadelphia, where C. Everett Koop, the pediatric surgeon who will go on to become President Ronald Reagan’s surgeon general, has just repaired Stephen’s hernia and undescended testicle—both additional manifestations of congenital rubella.41 Here, one year later, is Stephen in a red gown with Mrs. D’Arienzo, clutching his diploma as he graduates from the Beachwood Nursery School.
What is striking in many of these early photos is the liveliness, even impishness, that projects from Stephen’s eyes and from his grin—how very much like a typical boy he seems. Looking at them, it is hard to imagine that he inhabits a world of near darkness and near silence.
After a long and painful struggle, the Wenzlers found Stephen a place at the Perkins School for the Blind in Watertown, Massachusetts, whose most famous graduate, Anne Sullivan, taught Helen Keller to read and write. Stephen arrived there at age seven and remained there through high school.
He grew up to be an exceedingly bright and gifted man who would live a life of unrealized potential, frustrated ambition, and loneliness. Some of this would be the result of his own failings. But most would be attributable to a society that could not see what he might have been.
CHAPTER THIRTEEN
The Devils We Know
Philadelphia and Hamburg, Pennsylvania, 1965–67
Marburg, Germany, August–November 1967
In retrospect, it is amazing that cells [freshly harvested from monkey kidneys] were thought to be the safest choices. Considering all the microbial agents to which animals are exposed, the subsequent events were predictable.
—Stanley Plotkin, 19961
As he finished the trial on the toddlers at St. Vincent’s Home for Children early in 1965, Plotkin knew that he needed to weaken the RA 27/3 virus further so that it would stop causing rubella in vaccinees—but not so much that it would no longer cause a vigorous immune response. And he knew that he needed to waste no time doing it. He was a generous and outward-looking man; a timely vaccine might forestall the next epidemic and with it the heartbreak and the physical suffering he had witnessed at such close range in London and in Philadelphia. He was also competitive. And he was sure that his rivals, like him, were striving to develop a vaccine before anyone else.
Plotkin was correct. His competitors were pushing ahead just as quickly as he was. Maurice Hilleman, the tough Montanan who headed vaccine research at Merck, had already, in January 1965, completed extensive animal safety tests and was injecting the company’s experimental rubella vaccine into intellectually disabled children living in institutions in and around Philadelphia, in northern Pennsylvania, and in Delaware. (The Pennsylvania Association for Retarded Children gave the in-state trials its blessing.)2 For drug companies like Merck, beating the competition to a rubella vaccine would mean a big new market for a product that would be much in demand. It was not clear whether the CDC would recommend that a rubella vaccine be given to women of childbearing age or to small children as part of routine childhood vaccinations. But either group—the approximately 3.6 million children born annually in the mid-1960s or the roughly 39 million girls and women then of childbearing age—amounted to a huge number of customers.
This fact was not lost on other drug firms. Across the Atlantic in Genval, Belgium, virologists at a company called Recherche et Industrie Thérapeutiques were hard at work developing their own rubella vaccine, with a virus captured from the urine of a ten-year-old girl who was ill with rubella. Soon a St. Joseph, Missouri, company named Philips Roxane, a subsidiary of Philips Electronics and Pharmaceutical Industries Corporation, would begin developing yet another competing vaccine.
And then there were the Division of Biologics Standards scientists. In the DBS’s utilitarian redbrick building perched on a rise in the middle of the NIH campus in Bethesda, Maryland, Paul Parkman and his boss, Harry Meyer, were preparing to launch human studies of their “high passage virus,” HPV-77 rubella vaccine—made from the virus that Parkman had captured from the throat of a young soldier at Fort Dix, New Jersey, and then weakened by growing through seventy-seven sequential cultures of African green monkey kidney cells.
Unlike Plotkin, Parkman and Meyer had obtained formal permission from the DBS to experiment with the HPV-77 vaccine in human beings. This permission, called an Investigational Exemption for a New Drug, was new in the regulatory world. It had been instituted as part of a 1962 tightening of prescription drug–approval laws that was spurred by a fresh tragedy.
In a horrible episode in the late 1950s, 1960, and 1961, the drug thalidomide was widely prescribed—or available over the counter—as a sedative and for morning sickness in pregnant women in Europe, Canada, Australia, Japan, and many other countries. As a result, thousands of babies were born with missing or flipperlike limbs and other birth defects. One U.S. regulator, a woman named Frances Kelsey who was a drug inspector at the Food and Drug Administration, single-handedly prevented thalidomide from being approved for market in the United States. It was, however, taken by hundreds of pregnant American women in company-sponsored drug trials. The congressional reaction to the thalidomide tragedy included a new legal requirement that drugs be proven effective as well as safe before they could be marketed.3,4
The DBS did not handle approvals for drugs like thalidomide; they were medicines and were separately regulated by the FDA. But it did regulate vaccines. Just one DBS employee—a chubby, good-natured, cigar-smoking physician named Joe O’Malley—handled, with the help of his assistant, all of the applications for permission to test new vaccines in people.5
Roderick Murray, the taciturn, inscrutable DBS director, briefly considered moving Parkman and Meyer to the NIH’s National Institute of Allergy and Infectious Diseases, to get them out of the DBS and avoid the appearance of a conflict of interest.6 But the pair didn’t want to be slowed down by a move. And Murray didn’t want to slow them down. With the pain and suffering of the 1964 rubella epidemic now in full public view in the form of thousands of damaged newborns, the DBS was under tremendous pressure to produce and approve a rubella vaccine before the next epidemic arrived.7
In the United States rubella spiked with regularity, every six to nine years. Before the record-breaking 1964 epidemic, the last substantial outbreaks had been in 1958 and 1952. Now 1970 began to loom as the year when another epidemic might well descend—the year by which a rubella vaccine needed to be in use. Murray decided that it would be enough to erect a “paper barrier”—the Investigational Exemption for a New Drug—to shield Parkman and Meyer from allegations of conflict as they went about developing their rubella vaccine in the very division that was the gatekeeper for the U.S. vaccine market.8
In October 1965 Parkman and Meyer launched the human first trial of the HPV-77 vaccine, at the Arkansas Children’s Colony, a state school for the intellectually disabled in rural Arkansas.9 There seven hundred students lived in small groups in widely scattered cottages, allowing them to be isolated for vaccine studies. “Children were selected for vaccination only after their parents or legal guardians had been fully acquainted with all the details of the projec
t and had given written permission,” Parkman, Meyer, and their colleague Theodore Panos wrote in the resulting publication.10 (Panos was the chairman of pediatrics at the University of Arkansas School of Medicine, where Meyer had gone to medical school; it was through him that Parkman and Meyer arranged for the trial to be held at the Arkansas institution.)11
Decades later Parkman recalled that he and Meyer had also sought approval from the NIH Medical Board Committee, made up of officials of the several NIH institutes and of the Clinical Center, the huge research hospital on the NIH campus. The board could be consulted when NIH scientists were undertaking “any nonstandard, potentially hazardous procedure.”12 However, whether to enlist the board was left to the discretion of the scientists undertaking a study. Parkman and Meyer’s proposed trial was unusual in that it was being conducted off campus, not at the Clinical Center. What was more, Parkman remembered, “It was sort of an iffy thing. You could start a rubella epidemic, you know? Things could go wrong. These were retarded children in an institution and that might not be the best thing. Maybe the parents wouldn’t understand—a whole lot of things could go wrong. So for the medical board . . . it was a little bit of a struggle. I think we got approval by a narrow margin.”13
At the Arkansas Children’s Colony Parkman and Meyer injected the HPV-77 vaccine into thirty-four children living in four different cottages and left thirty antibody-lacking children unvaccinated. The unvaccinated children shared the vaccinees’ living quarters and would serve as vulnerable contacts; if the vaccine virus was contagious, they could well catch the disease.
In stark contrast to Plotkin’s study at St. Vincent’s, none of the vaccinated children developed rubella, with its rash, swollen lymph nodes, and fever. The researchers did detect the rubella virus in throat swabs from two thirds of the vaccinated children—meaning that they might have spread the disease even though they didn’t get sick. But that did not happen. None of the unvaccinated, antibody-lacking children living with the vaccinees got rubella. What was more, 94 percent of the vaccinated children developed antirubella antibodies, the sought-after result.14 It was an auspicious launch for the HPV-77 vaccine.
The Vaccine Race Page 25