The Vaccine Race

Prologue

The role of the infinitely small in nature is infinitely great. —Louis Pasteur, nineteenth‑century French microbiologist

 
On October 9, 1964, a baby girl was born at Philadelphia General Hospital. She arrived early, when her mother was about thirty‑two weeks pregnant. The baby weighed 3.2 pounds and was noted to be blue, floppy, and not breathing. The only sign of life was her slow heartbeat. Nonetheless, she clung to life, and her seventeen‑year‑old mother named her.
 
One month later the baby was still in the hospital, and a doctor leaning close with a stethoscope heard a harsh heart murmur. A chest X‑ray showed that she had a massively enlarged heart because a hole in the muscular organ was preventing it from pumping blood efficiently. Doctors also noticed that the baby was staring into space, not fixing her gaze on anything. An ophthalmologist was called in. It emerged that the baby had cataracts blinding both eyes. Later other signs indicated that she was profoundly deaf, although a formal hearing test was never conducted.
 
In January 1965, after surgery attempting to repair one of the cataracts, the mother took her three‑month‑old daughter home. Nine days later the baby was back in the hospital with diarrhea. She remained in the hospital, where she suffered from recurring respiratory infections. She had trouble gaining weight, which is a common problem in infants with heart problems like hers. A psychologist who assessed her in July 1965, after a second heart defect was found, judged the nine‑month‑old to be the size of a two‑ or three‑month‑old infant and at about that stage of development; she couldn’t sit up or grasp an object placed in her hand.
 
The baby needed heart surgery if she was going to survive. Just before her first birthday, surgeons cut a seven‑inch incision in her chest wall and repaired her heart. After the operation she remained in the hospital. The chronic respiratory infections continued. The baby was sixteen months old and weighed eleven pounds when she died of pneumonia at 3:30 a.m. on February 18, 1966. She had lived all but nine days of her brief life at Philadelphia General Hospital.
 
The young mother had told the doctors something when she brought her daughter back to the hospital. When she was one month pregnant, she had had German measles, which is also known as rubella.
 
 
The early 1960s marked a coming of age for the study of viruses like the one that causes rubella—tiny infectious agents that invade cells and hijack their machinery in order to reproduce themselves. Biologists, with new tools in hand, were racing to capture viruses in throat swabs or urine or even snippets of organs from infected people and to grow them in lab dishes. Isolating a virus in the lab made it possible to make a vaccine against it. And making antiviral vaccines promised huge inroads against common childhood diseases like measles, mumps, and rubella, along with less‑common killers like hepatitis. The principle of vaccination is simple: if a person is injected with, or swallows, a tiny amount of a virus—either a killed virus or a weakened live virus—that person will develop antibodies against the virus. Then, if he or she is exposed in the future to the naturally occurring, disease‑causing form of the virus, those antibodies will attack the invader and prevent it from causing disease.
 
But if the concept is simple, making effective vaccines is anything but. In the early 1960s that reality was all too evident in recent tragedies. In 1942 as many as 330,000 U.S. servicemen were exposed to hepatitis B virus in a yellow fever vaccine that was contaminated with blood plasma from donors—plasma that was used to stabilize the vaccine. It turned out that some of those donors carried hepatitis B. About 50,000 of the vaccinated servicemen came down with the dangerous liver disease and between 100 and 150 died.3 In 1955 a California‑based company called Cutter Laboratories made polio vaccine with live, disease‑causing virus in it, paralyzing 192 people, many of them children, and killing ten. Every senior U.S. government employee involved in overseeing the Cutter process lost his or her job—right up through the director of the National Institutes of Health and the secretary of health, education, and welfare.
 
Then in the summer of 1961, Americans learned that the monkey kidney cells used to make the famous Salk polio vaccine harbored a monkey virus called SV40. Tens of millions of American children had already received contaminated injections, and while the jury was still out on the tainted vaccine’s long‑term health consequences, the unknown risks were weighing on regulators in the United States and elsewhere.
 
It was against this backdrop that, on a drizzly June morning in 1962, a young scientist went to work in his lab at the Wistar Institute of Anatomy and Biology, an elegant 1890s brownstone tucked in the heart of the University of Pennsylvania campus. Leonard Hayflick had just turned thirty‑four years old. A serious, slight reserved man with close‑cropped dark hair, Hayflick was a product of working‑class Philadelphia and was hungry to make his name. He was in love with biology and was plenty smart, he had come to believe—but that fact was far from appreciated. His boss, the famous polio‑vaccine pioneer Hilary Koprowski, saw him as a mere technician, hired to serve up bottles of lab‑grown cells to the institute’s impressive cadre of biologists.
 
This hadn’t deterred the ambitious Hayflick. The previous year the junior scientist had published a paper challenging a major piece of scientific dogma: the belief that cells grown in a lab bottle, if properly nurtured, would multiply forever. His findings had been met with skepticism from some outstanding biologists. Let the critics carp, he thought. Time would prove that he was right—that normal cells cultivated in the lab eventually died, just like human beings.
 
On this drizzly day, however, Hayflick’s mind was not on cell death but on cell birth. Today, he hoped, he was going to launch a group of normal human cells that would revolutionize vaccine making. He had been waiting months for this opportunity—waiting for the arrival of the lungs that would be the source of these new cells. Cells were needed to make antiviral vaccines because outside of cells viruses can’t multiply. And huge quantities of virus were needed to produce vaccines. Now, at last, the lungs were here in his bustling second‑floor lab, two purplish things floating in clear pink fluid in a glass bottle. They had traveled all the way from Sweden packed on wet ice, courtesy of a Koprowski colleague who was a top virologist at the prestigious Karolinska Institute in Stockholm.
 
Several days earlier a woman living near Stockholm had had an abortion. Most Swedish physicians frowned upon the procedure, but it was legal, even for not‑strictly‑medical reasons. The woman was sixteen or seventeen weeks pregnant and had several children already. Her husband, she told her doctors, was an unsupportive alcoholic. The decision was clear. She sought out a sympathetic gynecologist, Eva Ernholm, one of the rare women in Swedish medical ranks, to perform the procedure.
 
After the abortion the eight‑inch‑long, female fetus was wrapped in a sterile green cloth and delivered to a yellow brick outbuilding on the grounds of the National Biological Laboratory in northwest Stockholm. Here, in what they nicknamed the “monkey house” because it was also home to monkeys used in making polio vaccine, young PhD and medical students were occasionally called on to dissect out the lungs of aborted fetuses for shipping to the Wistar Institute. It wasn’t a pleasant task, but when their boss, Sven Gard, the top virologist at the Karolinska Institute, asked them to do it, they obliged, slipping on head covers and changing from white wooden clogs to red or blue ones when they entered the sterile rooms. Other employees, working nearby in a grand building with a spiral staircase, were responsible for packing the lungs on ice and transporting them to Bromma Airport for the transatlantic flight that would eventually bring them to Philadelphia.
 
 
Hayflick was convinced that compared with monkey kidney cells, which were often laden with lurking viruses, normal human cells would serve as cleaner, safer vehicles for making antiviral vaccines. And he knew that he was uniquely positioned to produce a long‑lasting supply of such cells. He had spent the previous three years perfecting the procedure that would do it.
 
Hayflick took the bottle with the little lungs floating in it into a tiny room off his lab—what passed for a “sterile” room in 1962. He picked up a pair of tweezers, dipped them in alcohol, and passed them through the flame of a Bunsen burner. He waited for them to cool and then, gently, one at a time, lifted the lungs out of the bottle and laid them on a petri dish. The underdeveloped organs were each no larger than his thumb above the knuckle. He assembled two scalpels, held the blades at right angles to each other, and began carefully slicing the lungs. He didn’t stop until he had cut them into innumerable pieces, each smaller than a pinhead.
 
Hayflick nudged the minute pieces of lung into a wide‑mouthed glass flask. The translucent pink fluid inside the flask looked innocent enough, but it was full of digestive enzymes from slaughtered pigs. These biological jackhammers broke up the “mortar” between the lung cells, freeing millions upon millions of them.
 
Later, he transferred the resulting cells into several flat‑sided glass bottles and poured nutritious solution over them. He loaded the bottles onto a tray, and walked them into an incubation room beside his lab. Here the temperature was a cozy 96.8 degrees Fahrenheit. He laid the bottles on their sides on a wooden shelf and closed the door carefully behind him.
 
The cells began to divide.
 
Hayflick already had a name for them: WI‑38.
 
 
The WI‑38 cells that Hayflick launched on that long‑ago summer day were used to make vaccines that have been given to more than 300 million people—half of them U.S. preschoolers. A copycat group of cells, developed using the method that Hayflick pioneered, has been used to make an additional 6 billion vaccines. Together these vaccines have protected people the world over from the gamut of viral illnesses: rubella, rabies, chicken pox, measles, polio, hepatitis A, shingles, and adenovirus—a respiratory infection that flourishes where people live in close quarters. (Every U.S. military recruit—more than 9 million of them since 1971—is vaccinated with an adenovirus vaccine made using WI‑38 cells.)
 
In the United States the rubella vaccine made in WI‑38 cells and still given to young children has wiped out homegrown rubella. That vaccine itself was developed at the Wistar, by Hayflick’s colleague Stanley Plotkin, in the midst of a devastating rubella epidemic that swept the country in 1964 and 1965. That rubella outbreak damaged tens of thousands of American babies—including the baby described above who lived most of her short life at Philadelphia General Hospital. This book will tell the story of that epidemic and of the race to develop a rubella vaccine that followed.
 
How can it be that these WI‑38 cells launched so long ago are still in use today? Partly because Hayflick made such a large initial stock of them: some eight hundred tiny, wine bottle–shaped ampules that he froze in the summer of 1962. Partly because the cells, when frozen, stop dividing, but then gamely begin replicating again when they are thawed—even after decades. And partly because of the power of exponential growth. Each petite glass vial that Hayflick froze contained between 1.5 million and 2 million cells. And the cells in those vials had, on average, the capacity to divide about forty more times. Early on, Hayflick did the math and determined that the newly derived cells covering the floor of just one of his small glass lab bottles, if allowed to replicate until they died, would produce 22 million tons of cells. He had created in those eight hundred vials a supply of cells that for practical purposes was almost
infinite.
 
And so, in addition to their use in vaccine making, the WI‑38 cells became the first normal, noncancerous cells available in virtually unlimited quantities to scientists probing the mysteries of cell biology. Because they were easily infected with so many viruses, they became important to disease detectives tracking viruses in the 1960s, before more sophisticated technology came along. Biologists still reach for WI‑38 cells when they need a normal cell to compare against a cancerous one or to bombard with a potential new drug to see if it’s toxic. The cells are also a workhorse of aging research, because they so reliably age and then die in lab dishes. They are held in such high regard by scientific historians that original ampules of WI‑38, and of polio vaccine made using it, are part of the collection of the National Museum of American History.
 
In the 1960s and 1970s the cells became the object of a bitter, epochal feud between Hayflick and the U.S. government, first over whether they were safe for vaccine making and then over who owned them. Hayflick’s preternaturally proprietary feelings for the cells—he once described them as “like my children”—led him to defiantly decamp from the Wistar to a new job three thousand miles away at Stanford University with the entire stock of WI‑38 cells. His escape infuriated the Wistar’s director, Koprowski, who had his own money‑making designs on the cells.
 
Hayflick’s flight with the cells would eventually make him the target of a career‑derailing investigation by the National Institutes of Health, which had funded his work deriving WI‑38. 8 Then, just as the tug‑of‑war over ownership of the WI‑38 cells peaked in the second half of the 1970s, profound changes occurred in attitudes and laws governing who could make money from biological inventions. In the space of very few years, biologists went from being expected to work for their salaries and the greater good—and nothing more—to being encouraged by their universities and the government to commercialize their inventions for the benefit of their institutions, the U.S. economy—and themselves.
 
Although the WI‑38 cells were launched long before these changes took place—and eighteen years before the Supreme Court decreed that a living entity like a WI‑38 cell could be patented—that is not to say that money has not been made from them. The huge drug company Merck in particular has made billions of dollars by using the WI‑38 cells to make the rubella vaccine that is part of the vaccine schedule for U.S. babies and preschoolers—ensuring more than seven million injections each year, not including those in more than forty other countries where the Merck vaccines is sold. The Wistar Institute too until the late 1980s enjoyed a handsome royalty stream from vaccines made by its scientists using the WI‑38 cells—including a much‑improved rabies vaccine that replaced sometimes‑dangerous injections. Cell banks today charge several hundred dollars for a tiny vial of the cells.
 
But the tale of the WI‑38 cells involves much more than money—and more too than the highly unusual story of Hayflick, the iconoclastic scientist who launched them. It involves the silent, faceless Swedish woman whose fetus was used to derive the cells without her consent. It involves the dying patients into whose arms the WI‑38 cells were injected with the misguided aim of proving that the cells did not cause cancer. It touches on the ordinary American chil dren who perished from rabies before WI‑38 cells were used to make a better vaccine, and on the U.S. military recruits who died from adenovirus infections when the Pentagon stopped giving service members the vaccine against that virus, made in WI‑38 cells. It involves the abortion opponents who, now as then, harbor a deep moral abhorrence of any vaccines made using human fetal cells.
 
It is also about Stanley Plotkin, a young scientist who stubbornly fought powerful competitors by using the WI‑38 cells to develop a superior rubella vaccine—and the purely political roadblocks that nearly stopped him. And it is about the one‑, two‑, and three‑year‑old orphans on whom Plotkin tested that vaccine, with the blessing of the archbishop of Philadelphia. It involves the irony of the untold millions of miscarriages, still births, and infant deaths that have been prevented by a rubella vaccine made using cells from an aborted fetus.
 
 
These pages are full of medical experiments that we find abhorrent today. Young, healthy prisoners are injected with hepatitis‑tainted blood serum; premature African American babies with experimental polio vaccine; intellectually disabled children with untried rubella vaccine.
 
We recoil in horror. It is easy to condemn out of hand the scientists who conducted these experiments on the most voiceless and powerless among us. And their actions were in many cases horrifying and inexcusable. But it is more instructive—and perhaps more likely to prevent similar betrayals in the future—to try to understand why they did what they did.
 
The experiments began, in large part, during World War II.
 
They grew out of the exigencies of the war, when an ends‑justify‑the‑means mentality took over in U.S. medicine in the interest of keeping soldiers healthy at the front, because civilization was at stake. Everyone was expected to do their part for the cause—even institutionalized people with grave disadvantages or disabilities. When the war ended, the mentality didn’t. In the two decades following the war and in several cases into the 1970s, medical researchers experimented on people—almost always vulnerable people—making them sick and sometimes killing them, in the full light of day.’
 
These scientists were perceived and perceived themselves as part of a heroic quest to defeat disease. They were ambitious, driven, and well funded by the U.S. government. And they got results.
 
During World War II and in the two decades following it, childhood mortality declined strikingly, in large part because of dramatic inroads against infectious diseases. Antibiotics that became available in the 1940s turned often‑lethal diseases like typhoid fever and dysentery into less‑grim maladies and slashed both the incidence of tuberculosis and its lethality. Vaccines against diphtheria, polio, and whooping cough hammered these childhood killers. Infectious diseases as a cause of death among children were rare by the middle of the 1960s.
 
The men who conducted unethical human experiments in this era were not medical outliers. They were top physicians and researchers operating with the full backing of the U.S. government, private funders, and esteemed medical schools and hospitals. Only in 1966, when a landmark paper in the New England Journal of Medicine exposed the harm being done to powerless people in scores of experiments, did the government begin to implement protections.
 
The surgeon general launched a requirement that people give their informed consent to participate in research studies funded by the U.S. government’s health agencies and that researchers win preapproval for their human experiments from an independent committee charged with examining the risks and benefits to participants. Since then, those protections have been strengthened, expanded, and written into U.S. law. Today’s system of human‑subject protections is not perfect. In fact, it has serious shortcomings and vocal critics. But it is worlds better than the feeble effort that existed half a century ago.
 
To remove the history of human exploitation from vaccines and medicines that were developed in the postwar era is impossible. The knowledge that allowed their development is woven into them. Should we therefore shun them? Definitely not. Take rubella as a case in point. As I write this in the summer of 2016, 1,700 babies in a dozen countries have been born with abnormally small heads or other brain malformations; their mothers were infected with the Zika virus while pregnant. Zika’s emergence is a vivid reminder of what life was like in the United States in 1964. Then, there was no rubella vaccine and tens of thousands of American babies were born gravely damaged by the rubella virus, which selectively attacks fetuses in the womb. Like Zika, rubella homes in on the brains of fetuses; it also ravages their eyes, ears, and hearts. But today, thanks to the vaccine that was perfected in experiments on institutionalized orphans and intellectually disabled children, indigenous rubella has been wiped out in the Western Hemisphere. Cases occur only when they are imported from other countries.
 
We can’t turn the clock back. The only way we can partially make it up to these children and untold others is to honor their contribution by making it meaningful—by continuing to vaccinate against rubella and the other diseases that made childhood a perilous journey before vaccines against them existed. We need also to strive constantly to enforce and improve the regulations and laws that protect research subjects so that in the future such abuses never happen again. We might also remember, when judging the men who abused vulnerable human beings in order to advance both human health and their own careers, that they were creatures of their time, just as we are of ours. Rather than training our criticism on them, it might be more useful to ask ourselves this: what are we doing or accepting or averting our glances from today that will cause our grandchildren to look at us and ask, How could you have let that
happen?