Hayflick also took his findings to Koprowski. He briefed his boss on the many disease-causing viruses that infected the diploid cells, and their consequent potential for vaccine making. He told him about their normal chromosomes and their lack of cancerous transformation. And he laid out the audacious claim that the paper would make—that cells aged and eventually died in lab dishes—throwing into question Carrel’s “immortal” chicken heart and upending decades of received wisdom. “The next thing you’re going to tell me is that these lung cells of yours are breathing,” Hayflick remembers Koprowski saying at one point, Hayflick recalled in a 2014 interview.37
Nonetheless, the junior scientist invited his boss to join him and Moorhead as an author on the paper. It was a common practice, then as now, for top bosses to share authorship of papers, no matter how little of the actual work they had done. Koprowski demurred. His message was clear: Hayflick and Moorhead could own the paper, and the consequences of their temerity, all by themselves. He did agree, though, to do them the favor of drafting and signing a cover letter to Rous.
Hayflick sent off the paper with its cover letter and waited for what seemed like an eternity for a reply. While he was waiting, he fought back doubts. He was an unknown, a greenhorn, and no matter how good his data, some were going to dismiss him, to say that he had gone off the rails. Gey’s cautionary comment came back to haunt him. Was he, in fact, about to ruin his career?
Then an opportunity to buy some peace of mind presented itself. The huge Federation of American Societies for Experimental Biology was holding its 1961 annual meeting in nearby Atlantic City, New Jersey. In mid-April twelve thousand biologists would take over Gilded Age hotels like the Shelburne and the Marlborough-Blenheim and attend events like “The Thyroid Smoker” on the Skyline Terrace at the Traymore. Among the nearly three thousand talks to be given at the seaside resort, one of the most listened-to would be by Theodore “Ted” Puck.
Puck was a powerful, influential figure in cell culture. He was the Colorado-based scientist who had reported growing normal human cells from the skin samples of adult volunteers and from leftover surgical tissues. In the 1958 paper where he had reported this, however, Puck and his coauthor, Tjio, had not noted anything about the cells grinding to a halt. They had reported that the cells were still dividing heartily months after being launched, after dozens of replications.38 The implication was that they kept dividing indefinitely.
Puck, a Nobel-caliber biologist, was a man whom people turned to with their questions about how to best nurture lab-dish cells. He was known to be meticulous with his culture procedures and to independently test the ingredients of his medium to rule out contamination. (Hayflick had bought his ingredients off the shelf, and used them as is.) What was more, Puck was established as a brilliant man of science and a preeminent cell culturist. How could he have missed something as basic as cells dying, repeatedly, under his nose?
Hayflick wanted badly to put a single question to Puck, and the Atlantic City conference would give him his chance to do that. He just needed to screw up his courage to ask that question. In a 2012 interview Hayflick recalled Puck giving his talk in a big, packed hall. He thought that Puck was pompous, and at the same time, he felt intimidated. He forced himself to raise his hand. Puck called on him.39
Hayflick asked Puck if his normal human cells had ever ceased dividing and died, in spite of his assiduous attention to getting every component of the medium just right. Oh, sure, Puck replied. It happened from time to time. But it wasn’t a big problem. He would just go back to the freezer and thaw another ampule. That was all Hayflick needed to hear. He knew in that moment that Puck had looked at cells aging and dying in culture. But he hadn’t seen them.
Hayflick returned to Philadelphia full of confidence. It was a good thing, because ten days later, on April 24, 1961, Peyton Rous at last responded to the Hayflick-Moorhead paper, in a letter to Koprowski. His words were devastating. After apologizing for keeping the young authors waiting because of his busy spring meeting schedule, Rous reported that he and three other editors had read the manuscript and discussed it. Not only was it “too specialized” for the Journal of Experimental Medicine, but it was poorly structured and all over the map, bogged down with extraneous observations like the fact that the fetal diploid cells were susceptible to infection by many different viruses.
As for the authors’ proposal that cells aged and died in lab bottles, it “seems notably rash,” Rous wrote. “The largest fact to have come out from tissue culture in the last fifty years is that cells inherently capable of multiplying will do so indefinitely” if they’re properly cared for.
“What a broadside!” Rous observed of his own skewering of Hayflick and Moorhead. “Yet I write it with complete good will.”40
The man who in 1911 had been ignored and sometimes disparaged when he dared to suggest that viruses might cause cancer was, fifty years later, quite ready to poke holes in Hayflick’s audacious challenge to conventional wisdom. Yet Hayflick, with every stubborn, determined bone in his body, wasn’t for a moment going to be deterred. Three weeks after receiving Rous’s rejection letter, he sent the paper off to the less-venerable but still-respected journal Experimental Cell Research. That journal immediately accepted it for publication.
CHAPTER SIX
The Swedish Source
Philadelphia and Stockholm, 1961–62
I believe that life is chaotic, a jumble of accidents, ambitions, misconceptions, bold intentions, lazy happenstances, and unintended consequences, yet I also believe that there are connections that illuminate our world, revealing its endless mystery and wonder.
—David Maraniss, American author and journalist1
Sometime around the middle of 1961, an electrical freezer failed at the Wistar Institute. In it, according to Hayflick, were his frozen stocks of all twenty-five WI cell lines. The accident was discovered too late, and he lost all of the cells. One year earlier this would have been a major setback. By this point, however, it was mainly an annoyance. The cells had already yielded up their data; Moorhead had captured their chromosomes, in all their glorious normality, on film; and the paper had been written up, submitted, and accepted. It would appear in print in Experimental Cell Research in December 1961.2 And Hayflick, if he knew anything by now, knew just how to make replacements. So this wasn’t the end of the world. It was more like the beginning.
Hayflick had become firmly convinced of the potential of normal human fetal fibroblasts to improve vaccine making. In his view they were far superior to the expensive, sometimes-infected monkey kidney cells then being used to make polio vaccine—the only vaccine against a common viral illness that was then available. What was more, the human diploid cells could be infected with viruses for which vaccines didn’t yet exist or were in early development: common viruses including measles, chicken pox, and adenovirus, which frequently caused respiratory infections. Why not use the diploid cells to develop these new vaccines? Perhaps too his fetal fibroblasts could be used to improve on the two rabies vaccines that were then in use—one made from the pulverized brains and spinal cords of rabies-infected rabbits and the other from duck embryos. The first could have serious or fatal side effects. The second was sometimes ineffective.*
Hayflick determined that he would make a human cell strain that, if all went well, might become a gold standard for vaccine manufacturers. Not a strain launched, as he had launched the first twenty-five WI strains, with an exploring scientist’s tentativeness and curiosity, but one created with an eye to the future. A human diploid cell strain that vaccine manufacturers would embrace because of its pedigree: it would be free of viruses, free of cancer, and available in such quantities that running out of it would never be a problem.
To his mind such a gold-standard cell strain would have a huge advantage over, for instance, monkey kidney cells—which came from endless new pairs of monkey kidneys, each with its own risk of harboring some
unwanted virus. This was because the monkey kidney cells used to grow the polio vaccine virus were used just once, when they were freshly harvested from the kidneys of a newly slaughtered monkey. They were not allowed to divide repeatedly into ever-expanding quantities in lab bottles because regulators feared that the cells might turn cancerous with repeated divisions. As a result, tens of thousands of animals were imported and slaughtered each year to make polio vaccine.3
By contrast, a human cell strain derived from just one pair of fetal lungs and then allowed to replicate could be established as clean and safe at the beginning and then used without worry going forward. Not to mention that it would be far less expensive to provide: one pair of fetal lungs would be all that was needed. The costly obtaining and sacrificing of unending numbers of monkeys could stop.
Hayflick didn’t relish the prospect of going back to the gynecological surgeons at the Hospital of the University of Pennsylvania to ask for a twentieth fetus. For one thing, they were surgeons and had a limited interest in the esoteric projects of a junior biologist from the research institute across the street. For another, Hayflick knew that he was now going to need more than a fetus. He was going to need a family history of the parents of that fetus. It would have to be a clean history that would reassure vaccine makers there were no infectious diseases or cancer lurking in either parent—conditions that would “scare the hell” out of them, as Hayflick recalled in a 2012 interview.4 For this kind of cooperation he would need, on the upstream end of the abortion, a scientist who understood vaccine making and who therefore understood the importance of his project.
Sven Gard was a tall, solemn, soft-spoken Swede who had spent eight months on sabbatical at the Wistar Institute beginning in January 1959. He had occupied a lab across the hall from Hayflick’s and one door down. There he worked with the lights half dimmed—perhaps, Hayflick thought, because the low light made a man used to long northern winters feel at home.
The gray-eyed Gard was brilliant and renowned. Fifty-three years old, he was a father figure in virology who inspired both fear and adoration in his students. He was a power player of the sort that Koprowski regularly recruited to the institute. As chairman of virology at the famous Karolinska Institute in Stockholm, which awards the Nobel Prize in physiology or medicine, he was regularly a member of the committee that decided the winners of the coveted award. He had been instrumental in seeing that the prize went to Enders and his colleagues in 1954, for their discovery that polio virus would grow in many kinds of human cells and not only nerve cells, which opened up the quest for a polio vaccine.5
Gard himself had played a major role in his country’s intense drive to develop its own polio vaccine—an urgent goal because Sweden had a far-flung population and corresponding reservoirs of people who had never been exposed to the virus and had therefore never developed antibodies. That made the country particularly vulnerable to polio epidemics. In the 1950s Sweden had the highest number of cases per capita anywhere.6
Gard was a big believer in making human vaccines in human cells. He had been inspired by the idea during a 1952 visit to the Enders lab in Boston, where he saw the polio virus being grown in human cells. On his return to Sweden, where abortion had been legal since 1938, he began using cells from human fetuses obtained from hospitals in Stockholm to develop a Swedish polio vaccine.7 Unlike Hayflick six years later, Gard’s team of virologists didn’t try to coax the human fetal cells to replicate over and over again in lab dishes. Instead they used the fetal skin and muscle cells just once, infecting them with polio and then harvesting the virus-laden fluid that bathed the cells.
The skin and muscle were the only organs sufficiently big to give them enough cells to work with. But nonetheless they found that their efforts yielded ten times less vaccine virus than other scientists were producing using monkey kidney cells. While the Gard team did run one human trial, vaccinating two thousand children with the fetal cell–grown polio vaccine, it became clear that they could not generate enough of it to vaccinate a population of seven million people.8 Gard eventually bowed to the inevitable and used monkey kidney cells to make the Swedish vaccine.
Why didn’t Gard and his team simply grow huge numbers of the human fetal cells, coaxing them to replicate in lab dishes? “We never thought of it,” says Erik Lycke, who was a twenty-seven-year-old MD/PhD student working for Gard in 1953. “I don’t think anyone but Hayflick did.”9
The Swedes launched their monkey cell–produced polio vaccine in 1957. By 1964 the disease would be virtually eliminated in Sweden. In January 1959 Gard, who would later say he had been “breathing” polio research night and day, at last found time to respond to Koprowski’s invitation to take a sabbatical at the Wistar Institute. There he met, among others, Hayflick.
Hayflick recalled that Gard, who died in 1998, overheard him griping about getting fetuses from the gynecologic surgeons at HUP—the hassle of it and their lack of understanding of his purposes—and volunteered that if Hayflick should need fetuses in the future, it was easy for him to get hold of them back in Sweden.
Possibly as early as 1959, Hayflick began to take advantage of Gard’s offer, receiving occasional fetuses or fetal organs from Sweden. The time required in transit was not an obstacle; Hayflick had discovered soon after he began working with fetuses that living fetal tissue could be kept for five days at room temperature without dying. Minced tissue floating in growth medium lasted even longer: up to three weeks.10 Now, in 1961, confronted with the demise of his first twenty-five fetal cell lines, Hayflick turned again to the solemn Swede.
• • •
Eva Herrström had been working with Sven Gard since 1952 in the Karolinska Institute’s virology department, which was housed on the expansive grounds of Sweden’s National Bacteriological Laboratory. She had practically grown up there, where her father, Josua Tillgren, a prominent Stockholm physician, had hired her as an assistant lab technician in the summer of 1943, when she was just seventeen. She never left, and by the mid-1950s she had risen to become Gard’s top technician, a position she still held in 1961.
Gard’s lab wasn’t in the elegant main building designed by the famous modernist architect Gunnar Asplund but in a small, two-story yellow-brick outbuilding where it occupied the main wing of the second floor. The temporary-looking building was nicknamed the Monkey House because the other wing housed African green monkeys used to safety-test polio vaccine. The communal freezer was just outside the windowed door into the monkey wing; whenever someone deposited a sample in it, the monkeys shook their cages, raising a ruckus.
Humble digs or not, Herrström liked her work as Gard’s chief lab technician. He took an interest in all of his staff, inviting her and the other technicians when he presented lectures on scientific advances and crediting everybody for his or her contribution. Still, there was no mistaking who was in charge. There was little or no frivolity on the job, no happy hours, no practical jokes or undue familiarity. She knew that she would, until her dying day, call Gard “Professor.”
On this particular morning—April 24, 1961—Herrström climbed the metal stairs that ran up the outside of the building to the second floor to learn that a fetus would be arriving and that she needed to prepare its lungs for shipment to the United States.
When she had first worked for Gard almost a decade earlier, he had been trying to make polio vaccine with human cells. Then, Herrström had worked plenty with human fetuses, even learning how to expertly drain amniotic fluid that was used in cell-nurturing medium from the intact pregnant uteruses of cows that arrived regularly from the Stockholm slaughterhouse. But once Sweden moved to using monkey cells to develop the vaccine, that work with human fetuses had gone away—until lately, when Gard had begun asking her to prepare tissue for shipment to an American institute in Philadelphia.
Later, after she had donned a white gown and a car had delivered a tiny bundle wrapped in green surgical cloth, Herrström headed
for one of the sterile rooms in the middle of the floor. She washed her hands in disinfectant at the sink under the window, laid out her instruments, and sat down at the shiny linoleum table that was the lone piece of furniture in the room. She unwrapped the bundle.
It really was incredibly beautiful, this little fetus, with everything already in place. With this task she was being given a privileged glimpse into the creation of life. It helped to remember this as she picked up a scalpel. And it helped that she came from a family of physicians. You got used to it. You turned the tragedy around. You said to yourself that at least in this case, something life-giving might emerge from death.11 What shape that particular good might take in this instance Herrström didn’t know. But if Professor Gard said that scientists in Philadelphia needed fetal lungs, her job was to make sure they got them.
At home that night Herrström made a dinner of sliced reindeer meat and repaired her winter gloves. Before turning in at 9:30 p.m., she wrote in her diary: “Work 8.30-[5 pm]. Sent tissue to USA. Stressful.”12
The lungs that Herrström had earlier that day placed in medium in a small test tube, and the tube that she had then placed in a thermos, and the thermos that had then been packed in a box, on wet ice, were well on their way by then to Philadelphia.
• • •
It’s probable, although not certain, that the lungs that Herrström removed from that fetus on that spring day went on to become the next cell strain that Hayflick created. (By this point Hayflick was working only with lungs because they were readily dissected and their fibroblasts seemed particularly hardy in culture.) It’s also possible that those lungs didn’t work out. Perhaps delays caused them to die in transit, or perhaps they were inadvertently infected. Because scarcely one week later Herrström recorded in her diary that she had shipped more tissue, from a new fetus, to Philadelphia: “Tissue to the USA at 12 (noon). Took all morning to prepare.”13
The Vaccine Race Page 11