“It was a bitter, bitter disappointment,” Hayflick said emphatically during a 2012 interview, sounding as if he could still taste the letdown nearly seventy years later.12 “It was clearly a consolation prize. The first prize was given to a girl ‘apple polisher’ whose mother sent pies and gifts to her teachers.”
Temple University offered him a scholarship, but Hayflick didn’t accept it. He had his sights set higher. He wanted to go to the prestigious University of Pennsylvania, known to many as “Penn.” The university sat on an ivied hundred-acre campus in west Philadelphia that Hayflick’s father passed on the streetcar on his way to work. It was founded by Benjamin Franklin. It had a medical school as old as Harvard’s. And its history was peopled with leading medical and scientific figures like the physician William Osler and the anatomist and paleontologist Joseph Leidy. As he prepared to graduate from high school in January 1946, Hayflick applied to Penn and was accepted. His parents scraped together the nearly $250 that would pay his tuition for the spring semester.
Hayflick was a slight seventeen-year-old who stood less than five feet nine inches tall, and he found himself lost in a sea of former servicemen who were flooding the university on the GI Bill. Not only was Hayflick intimidated, but it soon became apparent that his parents couldn’t sustain the tuition, especially with his sister preparing to enter college too. So, shortly after his eighteenth birthday in May 1946, Hayflick took a leave of absence from Penn and enlisted in the U.S. Army. The support of the GI Bill would pay his tuition when he returned to Penn and—crucially, it would turn out—would also provide $75 in monthly living expenses.
In the army Hayflick learned to repair antiaircraft guns at the Aberdeen Proving Ground in Maryland and later landed at Fort Benning, Georgia, where he was chosen for a job as a teacher in a program that allowed army recruits to finish high school. The classes didn’t attract many soldiers, and Hayflick happily used the time in his small office to read. The position also came with a chauffeured car that he regularly summoned to drive him to the post’s library.
When Hayflick, by then almost twenty, reenrolled at the University of Pennsylvania in the spring of 1948, he was unsure what academic route to pursue. He took chemistry, math, zoology, and English; he also recalls enrolling in an accounting course at the Wharton School of Business. But he was soon distracted from his studies because his family was in crisis.
In the late 1940s Nathan Hayflick was persuaded by his nephew, Norman Silverman, to leave the Climax Company after three decades to join Silverman’s fledgling denture-designing business, Victory Laboratories, just over the Delaware River in Camden, New Jersey. Silverman was a charming, ambitious young entrepreneur and a relative newcomer to denture design. Nathan Hayflick was by now a master craftsman, but not a businessman. The partnership turned into a disaster as the two men’s personalities clashed. Nathan Hayflick fell into a depression that concerned his son so much that Leonard Hayflick began cutting classes, leaving Penn at midday to cross the river and take his father to lunch in order to get him out of the lab for a couple of hours.
Nathan Hayflick didn’t have an exit strategy: his old job at the Climax Company had been filled. He was a man in his late forties with a grade-school education and a craft. Leonard Hayflick decided there was only one way out for his father. Nathan Hayflick needed to go into business for himself, bringing his loyal clientele of dentists with him. While a student at Penn, Hayflick set about building his father a laboratory. He had absorbed enough of the denture-designing craft by osmosis to be sure that he could do it. The entire effort would have to be accomplished on a shoestring: the four Hayflicks were now surviving on the $75 in monthly living expenses that the GI Bill provided to Leonard Hayflick.13
Through a distant relative, Hayflick located rental space above the Latin Casino, a popular center-city nightclub. With the help of Al Ketler, a close friend and fellow Penn student who was skilled in carpentry and plumbing, Hayflick equipped the lab with a plaster bench, grinding instruments, water lines, and a casting machine that he and Ketler built out of a fifty-gallon steel drum. He and Ketler sneaked into the ancient building’s basement, confronted a tangle of wires and pipes, selected a likely-looking gas pipe, and cut it with a metal saw, allowing them to run an extension to supply the lab’s Bunsen burners. “We were young and not too smart,” Hayflick recalled in a 2014 interview. “Fortunately, we didn’t die.”14
What did suffer were Hayflick’s grades. He didn’t think he had a choice; it was a matter of his family’s economic survival. In the end, the Nathan Hayflick Dental Laboratory opened, the senior Hayflick got back on his feet, and his son turned back to his studies.
CHAPTER TWO
Discovery
Philadelphia and Galveston, 1948–58
Oh, you may be sure that Columbus was happy not when he had discovered America, but when he was discovering it.
—Fyodor Dostoevsky, The Idiot
Early during his studies at the University of Pennsylvania, Hayflick enrolled in an introductory course in what was then called bacteriology.
On his first day in the lab, a technician walked in carrying something that changed Hayflick’s life. It was a tray of test tubes containing a nutritious, gelatin-like substance called agar, which was a dull chicken-soup color. The test tubes had been tilted so that the agar, initially poured into the tubes in liquid form, solidified on a slant, maximizing the surface area available for bacteria to grow on. The technician had then used a fine needle to inoculate each tube with a different kind of bacterium, dragging the needle in a wave pattern along the yellow brown agar to “streak” it. What the young Hayflick saw was the resulting bacterial growth. The slants were streaked with a rainbow of colors, from yellow to purple, green, white, and pink.
Hayflick was blown away. He decided on the spot to major in bacteriology. (The discipline would soon be relabeled “microbiology,” in order to encompass viruses as well as bacteria.)
Hayflick’s love affair with microbes began at the dawn of a golden age for the study of viruses. The study of bacteria—bigger organisms that can survive independently outside of cells—was older. Scientists had been growing and examining bacteria in lab dishes since the late 1870s, when a German microbiologist named Robert Koch developed practical methods of growing pure cultures of bacteria in the lab. Koch also decisively laid out the steps that biologists needed to take to prove that a given bacterium was causing a particular disease. Biologists began to link specific bacteria with diseases, to understand how they were transmitted, to track outbreaks, and to launch the first therapeutic salvos against bacterial banes like diphtheria and syphilis.
The ease with which bacteria could be grown in lab dishes was vital not only for studying them but also for the discovery and testing of the antibiotics that were new miracles in the late 1940s: drugs like sulfa and streptomycin. The most famous among these was discovered when a short, slight Scotsman named Alexander Fleming noticed something strange on an agar plate on which he was growing Staphylococcus bacteria in his lab at St. Mary’s Hospital in London. A mold had accidentally taken root on the petri dish, and the bacteria, which were thriving elsewhere on the dish, wouldn’t grow anywhere near the mold. That moldy invader, it emerged, made a substance that Fleming named penicillin.
Virology was a slightly younger and decidedly less well-equipped science. Viruses had been known to exist since the early 1890s, when a young Russian scientist named Dmitry Ivanovsky took sap from the yellowed, stunted leaves of plants with tobacco mosaic disease and passed it through a filter containing pores too tiny for bacteria to slip through. (Bacteria are enormous compared with viruses. Consider that HIV, a typical-sized virus, is a mere golf ball compared with the soccer ball that is Streptococcus pyogenes, the diminutive bacterium that causes strep throat today but regularly killed kids when Hayflick was a child.)
The filtered fluid from the diseased tobacco leaves was able to infect other, h
ealthy tobacco plants.1 Soon a Dutch botanist, Martinus Beijerinck, who had done similar experiments, demonstrated that whatever was causing the tobacco-plant disease could reproduce itself but needed living cells in which to do so.2 He became convinced that the disease-causing entity was a liquid, and he christened it with a Latin name, “virus,” which means “slimy fluid.”
The same year, 1898, a pair of German scientists, Friedrich Loeffler and Paul Frosch, found that they were able to pass along a devastating animal affliction, foot-and-mouth disease, by taking fluid from the sores of infected calves, filtering it, and using the filtrate to infect other animals—the first proof of animal infection by these mysterious new entities, which scientists began calling “filterable agents.”3 (It would be some time before the term “virus” came into common use.) The German duo also surmised, correctly, that the infectious agent wasn’t a liquid but a particle so small that the filter did not capture it.4 The pair also developed what was probably the first killed-virus vaccine, taking fluid from the sores of infected animals, heating it to destroy its infectivity, and injecting it into nonimmune cows and sheep, the overwhelming majority of which were then protected from the disease.5
In the next half century some dozen viruses that cause human diseases were identified, including the viruses that cause yellow fever, rabies, polio, and influenza. Dozens of animal and plant viruses were also found. In 1927, Thomas Rivers, an eminent American microbiologist, defined viruses as “obligate parasites,” meaning that they could reproduce only by invading living cells.6 In 1928, the year of Hayflick’s birth, Rivers published Filterable Viruses, a collection of essays of which he was editor, describing the roughly sixty-five viruses that had been identified to that date.7
But identifying viruses was hardly tantamount to understanding them, never mind fighting them. And the fact was, for the first half of the twentieth century, scientists investigating human-infecting viruses were hobbled by the difficulty of getting at them. That was because, unlike bacteria, which live happily and independently in lab dishes as long as they’re nourished with nutritious substances like agar, viruses need living cells in order to survive.
At its most basic, a virus consists of a circular or linear thread of genetic material—DNA or its chemical cousin, RNA—and a protective protein coat. It reproduces itself by invading a cell and forcing the host cell’s machinery to make tens, hundreds, or thousands of copies of the virus in one huge burst, sometimes in the space of minutes. These new viruses—each virus is called a virus “particle”—then bud or burst out of the cell and proceed to invade other cells. (Some viruses can also move directly from cell to cell.)
Despite their formidable talent for hijacking, viruses are helpless on their own. They are not independent organisms that propel themselves around, eat, digest, excrete waste, or have sex. Their sole business is to invade living cells so they can reproduce. So while they can survive on nonliving objects and surfaces for hours, days, weeks, and sometimes months, they are merely inert chemicals when they are sitting in, say, a test tube. It is “only in the interior of a living cell [that a virus’s] hidden forces are liberated,” the Swedish virologist Sven Gard—who will play a role in this story—observed as he presented the Nobel Prize in 1954.
But how then to study human viruses? Sometimes scientists relied on human heroism. Walter Reed, the famous U.S. Army physician who proved that yellow fever was caused by a mosquito-borne virus, did so by enlisting volunteers who were willing to be bitten by mosquitoes that had recently fed on yellow fever–infected patients. One of Reed’s medical colleagues, Jesse Lazear, was infected and died in that decisive experiment in 1900.
Sometimes virologists could use living animals to study human diseases, like the group of British investigators who, during an outbreak of influenza in 1932, noticed that some of their furry laboratory ferrets, being used for other purposes, were sneezing. They had caught human influenza from the sick scientists. (Later the reverse also happened.) From then on, the group studied influenza by using a pipette to drop throat garglings from infected people onto ferrets’ noses. When the disease was at its height, they would sacrifice the ferrets and study their tissues. But observing the damage to animals—rather than observing the virus itself—was hardly satisfactory. And yet viruses were too small to be seen with the light microscopes that were then available. Besides which, many human viruses did not infect other animals.
In some limited cases scientists succeeded in growing human viruses in lab dishes, using a little-understood art called tissue culture. Tissue culture today is more commonly called cell culture. It means growing living cells in the laboratory, outside of the animals or plants that they came from. (It will play a central role in this book.) Ross Harrison, a brilliant, driven biologist then at Johns Hopkins University, is credited with launching tissue culture in 1907, by growing bits of frog embryo brain in the lab. By nourishing the frog brain cells with fluid from the frogs’ lymph glands, he kept the cells alive for weeks.
In the following three decades virologists would manage, with difficulty, to grow several viruses in tissue culture—for instance, in fresh, minced hen’s kidney bathed with blood serum (the liquid, noncellular part of blood). But their successes were sporadic and inconsistent. Soon the viruses would die out in their dishes. Over these decades the only practical accomplishment to come from the use of tissue culture in virology was this: in the 1930s Max Theiler, a South African–born virologist at the Rockefeller Institute in New York City, weakened the human yellow fever virus by growing it in minced chicken embryos, developing the yellow fever vaccine that is still used today.
This achievement was the exception when it came to viruses—in stark contrast to the strides being made against their bacterial counterparts. By the middle of the twentieth century, bacterial diseases were being beaten back by vaccines against once-common killers like diphtheria, tuberculosis, and whooping cough—and by antibiotics. These new wonder drugs shut down bacteria, but they didn’t target viruses, which, because of the way they co-opt the native machinery of host cells, are harder to take aim at without producing off-target side effects. The first antiviral drugs wouldn’t begin to be developed until the 1960s. And so, as Hayflick stood, transfixed, before those rainbow streaks in a bacteriology lab at the University of Pennsylvania, viral illnesses like measles, rubella, and hepatitis remained stubborn, dangerous banes—with polio the most visible and frightening among them.
• • •
The discovery that changed everything for virus hunters happened in 1948, just as Hayflick returned to Penn from the army. In the spring of that year, an unassuming, middle-aged scientist was laboring in a small lab at the Boston Children’s Hospital. John Enders came from a wealthy New England banking family. He enjoyed the poetry of T. S. Eliot, favored old tweed jackets, and had flown rickety biplanes as a flight instructor during World War I. He had failed as a real estate agent before developing a passion for biology and earning a PhD at Harvard. Enders and his younger colleague Thomas Weller, a pediatrician from a family of physicians, had been trying to improve tissue-culture techniques for a decade—interrupted by World War II, when Weller had served in the Army Medical Corps. They had lately been joined by a third virus hunter, Frederick Robbins, an infectious-disease physician who had served in the army in North Africa and Italy, winning a Bronze Star. The trio was about to break open the world of virology, allowing scientists to grow a plethora of viruses in many tissues in lab dishes. With the application of their techniques, viruses would no longer die out in their dishes but would continue to multiply, allowing for study—and vaccine making.
Apart from sheer, dogged hard work, there were three key developments that led to the Enders team’s success. First, tissue culturists were figuring out, slowly, how to improve the nourishing solutions that they used to keep cells alive in lab dishes. Second, the Boston scientists put to good use a roller-tube system invented fifteen years earlier. So
mething like a Ferris wheel, it slowly rotated cells in test tubes, lying on their sides, eight to ten times every hour. This allowed the cells to be first washed in nutrient fluid, then exposed to air, in an attempt to mimic the conditions in the human body with its ceaseless flow of oxygenated blood to and waste removal from cells. Third, and crucially, as the 1940s progressed, Enders also took advantage of a new tool: antibiotics, which he began religiously applying to his test-tube cultures. He hoped, correctly as it turned out, that they would eliminate contaminating bacteria but leave viruses thriving.
One day in March 1948, Enders made a seemingly off-the-cuff suggestion to his junior partners. It involved polio. Poliovirus had resisted attempts to corral it in culture dishes, with this exception: In the mid-1930s a brilliant, ambitious young scientist named Albert Sabin, working with his senior colleague Peter Olitsky at the Rockefeller Institute in New York City, managed to grow polio in nerve cells from the brains and spinal cords of two aborted human fetuses.8 (The spinal cord, like the brain, is composed mainly of nerve cells, called neurons.) The duo had obtained the three- to four-month-old fetuses from a physician colleague at Bellevue Hospital, dissected their organs, and stored them in a lab refrigerator. Their experiment was groundbreaking not only for what it reported about polio but also for being one of the first published studies to use human fetal tissue in the lab.
In the 1930s abortion was a crime in every U.S. state in most circumstances.9And indeed, most of the estimated 800,000 abortions that were conducted annually during the economically stressed 1930s were illegal.10 The exceptions were known as therapeutic abortions; they reflected an unwritten understanding between legal authorities and physicians that the latter would be allowed to conduct abortions they deemed medically necessary or advisable. Therapeutic abortions were conducted at abortion clinics or medical offices by licensed physicians. But this was not an age of placard-carrying demonstrators outside clinics. These were procedures done out of public view. In the same way, fetal tissue research was conducted out of sight of the public and at the will of researchers.
The Vaccine Race Page 3