What is certain is that by the autumn of 1961 Hayflick had launched his twenty-sixth diploid cell strain, from the lungs of a male fetus aborted sixteen weeks into pregnancy and sent to Philadelphia from Gard’s lab in Sweden. By that October he had taken time-lapse photos of the new WI-26 cells being attacked by polio virus in a lab dish.14
Hayflick’s timing in launching the new fetal cell strain was near perfect. He produced and froze what he thought would be plenty of the fibroblasts—about two hundred ampules of them, each containing up to two million cells—shortly before the December publication of “The Serial Cultivation of Human Diploid Cell Strains,” the paper that announced to the world his discovery of the Hayflick limit and his cultivation of those first twenty-five normal fetal cell strains. Readers, of course, didn’t know that those cells had since died in the freezer failure.
Demand for his human fetal cells soared when the landmark paper was published. With the dozens of viruses that Hayflick had demonstrated to infect the cells, virologists were keen to get hold of them for experiments on the nature of these viral diseases. Companies hoping to launch viral vaccines wanted them. Basic biologists too sought them for all manner of study on the workings and behavior of normal cells in lab dishes. With the new WI-26 cells on hand, Hayflick was ready.
Soon he was handing out ampules of WI-26 left and right to biologists, virologists, and companies aiming to create vaccines against measles, adenovirus, and polio. But before he knew it, to his chagrin, Hayflick began running out of ampules—an embarrassing fact, since he had been determined to make a plentiful supply. What Hayflick hadn’t reckoned on was the demand for the cells. Had he seen it coming, he might have been more conservative, thawing one ampule at a time and expanding its contents through several generations in the incubation room, then sending out the much-more-numerous resulting cells. Giving away the ampules themselves was like giving away his seed corn.
“As a consequence of the unanticipated and unprecedented demand” for WI-26 cells, he would write in the Wistar’s next biennial report, “depletion” of his stocks had occurred.15
He needed to begin again—again. He needed to create a human fetal cell strain that would outlast the current, seemingly bottomless demand, for this new kind of normal, diploid cell. Fortunately, Gard continued to be good on his word. This time Hayflick asked Gard for the lungs of a female fetus, to ensure that if any of the male WI-26 cells he had launched into labs around the world became mistakenly mixed with the new cells during an experiment, the problem could be made quickly apparent by looking at the cells on a microscope slide: in a female cell strain, there should be no Y chromosomes present.
It wasn’t easy for Gard to deliver just the right fetus quickly. It had to be female. It had to be large enough—from a pregnancy three to four months along—to have readily dissected lungs that would yield enough tissue. And it had to be from a woman without health problems in her present or past. And so Hayflick waited. At last the lungs of a female fetus arrived from Sweden. Continuing with his numerical order, Hayflick named this next female lung-cell strain WI-27. Shortly after launching it, he handed a sample of the cells to Moorhead. He examined the cells and reported back that there was an abnormality in the WI-27 chromosomes. It was probably inconsequential, but “probably” was nowhere near good enough for vaccine makers, wary as they were of using cells that might be cancers in waiting. The strain was useless for vaccine-making purposes. Hayflick would have to go back to Gard once again.
At this point another scientist might have thrown up his hands and moved on to something else. The groundbreaking work deriving these normal human fetal cell strains was done. Hayflick’s methods were now published for all to see. What was more, he had launched a goodly supply of WI-26 cells into academic and commercial labs. Another scientist might have told colleagues and companies that if they wanted more normal cells, they could make their own. All it involved was engineering and practice. This line of thinking, however, was completely foreign to the dogged, determined, ambitious man who was Leonard Hayflick, who was set on delivering a lasting human diploid cell strain to the world.
Besides which, he was now working under a new obligation. In February 1962, as Hayflick was watching his supply of WI-26 cells rapidly dwindle, the National Cancer Institute, part of the National Institutes of Health, the U.S. government’s medical research agency, responding to the keen and obvious demand for Hayflick’s new breed of cells, entered into a contract with the Wistar Institute. Under it the Wistar—meaning, in practice, Hayflick—committed “to produce, characterize, and store human diploid cell strains” and to distribute them to all qualified investigators.16 From 1962 the Wistar began receiving from the National Cancer Institute annual contract payments of at least $120,000—nearly $1 million in 2016 dollars and about 10 percent of the Wistar Institute’s income from grants and contracts.17
Koprowski’s institute did need to make an initial outlay: In June 1962 the institute’s board of managers approved the Wistar director’s request for $8,000 to retrofit Hayflick’s “new Diploid Cell Laboratory” with a power line, extra air-conditioning, and plumbing that the NIH contract didn’t cover.18 Given the size of the contract, they must have felt that the payoff would more than justify that investment.
The language of the contract may seem dull, but it will become important. It stated in part that when the contract was terminated, “the contractor agrees to transfer title and deliver to the Government, in the manner, at the time and to the extent, if any, directed by the Contracting Officer, all data, information and material which has been developed by the Contractor in connection with the work under this contract.”19 In other words, while Hayflick would be the developer of new diploid cells under the contract, the government would own them, and when the contract was up, he would need to transfer any cells he had developed to the National Cancer Institute or place them wherever the agency directed him to put them. (In the case of cells, privately held cell banks are often used as cell custodians.)
And so, working under this new contract obligation, Hayflick, after the failure of WI-27, asked Gard for another female fetus. And once again he waited.
Hayflick made one more decision in the wake of the WI-27 disappointment. With the next human diploid cell strain he was going to change the numbering, because some scientists seemed to be carelessly confusing the numbers of earlier diploid cell strains. In order that going forward from WI-27 there would be no more such confusion, he would raise the “2” to a “3” and the “7” to an “8.” The next cell strain he created would be called WI-38.
• • •
On the warm, sunny morning of June 7, 1962, Eva Ernholm prepared for her job as an obstetrician/gynecologist at the Women’s Clinic in a hospital near Stockholm. One of few women in Swedish medicine in 1962, the thirty-seven-year-old Ernholm was an adventurer. As a medical student driven partly by an interest in Eastern religions, she had worked in a U.S. Eighth Army MASH unit in the spring of 1951, during heavy action in the Korean War, and returned to Korea with the Swedish Red Cross in 1953. She came back from her journeys bearing photos of herself bent over patients in a field hospital operating room and in fatigues surrounded by orphans, looking like she was having the time of her life.20
Ernholm was a blunt woman who knew her own mind and didn’t hesitate to speak it. Whether people liked her or her views—and they inevitably felt one way or the other—was a matter of indifference to her. She was impulsive and decisive and passionate. And, like Hayflick, she was not someone who was turned aside easily. An accomplished pianist, she had insisted on using a construction elevator to lift her grand piano to the penthouse apartment where she had taken up residence one year earlier.
Ernholm had abandoned an early interest in neurology to study obstetrics and gynecology and was a newly trained specialist when she took her hospital job in 1961. At the Women’s Clinic she shared a heavy workload with one other junior
doctor, monitoring pregnant women, delivering babies, cutting out uterine growths, and tying women’s tubes when they requested it. She also performed abortions.
Ernholm did not do this lightly. The following year, 1963, she would tell a newspaper reporter, “As a matter of principle, I am against all abortions that are not performed for medical reasons.” But, she added, “evidently there are situations when the social circumstances are so valid they don’t leave you any choice.”21
On this lovely June day Ernholm was confronting such circumstances, in a woman in her thirties who throughout this book will be called Mrs. X. Her medical history was uneventful, apart from childhood bouts with whooping cough, measles, and scarlet fever. Really, her only problem was that her last menstrual period had been in late January. Mrs. X explained that she already had several young children, and that her run-down husband, a working man, was often out of town for his job. When he was home, he wasn’t much use: he was an immature alcoholic who had done time in prison.
Ernholm took out her stethoscope and pressed it to Mrs. X’s chest and back. Her patient’s heart and lungs were clear, as they would need to be for the operation. Ernholm laid a hand on the woman’s soft abdomen. It was painless, Mrs. X confirmed, when Ernholm pressed it. Now came the stirrups and the hard metal of the speculum. It couldn’t be helped; one had to be sure that the patient was pregnant. Ernholm looked and then noted in Mrs. X’s record that the cervix, the mouth of the womb, was bluish—a telling sign of pregnancy. By feel and by sight, Ernholm judged that she was sixteen or seventeen weeks pregnant. She recorded this and wrote: “Indication for abortion: General weakness.” Then she added the details of Mrs. X’s home situation.
Sweden, where abortion had been a capital crime one hundred years earlier, had legalized abortion in 1938. The law enacted that year stipulated that women could have abortions in three situations: in cases of rape or incest; if delivering the child would cause “sickness” or “weakness” that seriously endangered the mother’s life or health; and for “eugenic” reasons, meaning that the mother or father was likely to transfer a serious hereditary disease to the child. (In this case the woman had to agree to be sterilized at the time of the abortion.) In 1946 the law was liberalized slightly to include “expected weakness” of the mother as one of the conditions that made an abortion permissible—the assessment that, given the mother’s living situation and circumstances, her health could seriously deteriorate if she was to bear and raise the child.22
In practice, however, getting an abortion in Sweden in 1962 was far easier said than done. A woman who sought to end a pregnancy had two choices. She could apply to the Medicinalstyrelsen—the Royal Medical Board—which regulated abortions for the government from an imposing nineteenth-century building in Stockholm. (It memorialized Swedish King Oscar I, an honorary member of the Swedish Academy of Sciences and a prolific father who sired eight children—three of them by mistresses.)
Alternatively, a woman could try to convince two doctors that she needed to end her pregnancy. One of the doctors was often a psychiatrist. The other was the surgeon who would perform the procedure. Most Swedish doctors opposed abortion and refused to help women get them, leaving thousands of women’s applications to grind through the slow-turning gears at the government’s Royal Medical Board, often pushing abortions well into the second trimester.
Mrs. X was seeking to end her pregnancy at just about the worst time possible for a woman in Sweden who wanted an abortion. In 1951 the Swedish Medical Association had adopted ethical rule IV, which said that the physician “should consider his duty to protect and preserve human life from its implantation in the mother’s womb.”23 The next year the chairman of the medical association, in the midst of a debate about whether to rescind the 1946 change that liberalized the law, said that abortion was in the same category as child murder.24 Swedish abortion rates then fell markedly, reached a low point in 1960, and scarcely budged in the next two years.
The day after Ernholm examined her, Mrs. X was wheeled into an operating room, where Ernholm performed what was called a “minor Caesarean section.” She cut through Mrs. X’s abdominal wall, carefully dissected the bladder free from where it lay high on the uterus, and cut through the wall of the uterus. She removed the fetus and the placenta, being careful not to leave any tissue behind. “The cavern was cleaned. Suture of the uterus in stages,” Ernholm wrote in the operative report. The fetus, she noted, “was 20 cm. long and female.”
That fetus was wrapped in a sterile green cloth, handed to an aide, and taken to a car for transport to the virology department of the Karolinska Institute.
• • •
A few days later, on a gray, drizzly morning in mid-June, Hayflick sat down in one of the tiny “sterile” rooms in his lab. Following a routine that was now deeply familiar, he dipped a pair of tweezers in alcohol, flamed them in a Bunsen burner, waited for them to cool, and then lifted two small, purplish chunks of tissue from where they floated in a glass bottle of clear pink solution. He laid them on a petri dish. Using a pair of scalpels held at right angles, working them like an improvised scissors, he minced the lungs into innumerable pinhead-size pieces. He deposited them in a flask, where a trypsin solution would break down the connective tissue holding the cells together, releasing millions and millions of individual cells.
Later he poured that mixture into several small glass tubes, stoppered them, and loaded them into a centrifuge, a round machine that sat on a pedestal with wheels and could be moved here and there around the lab. He turned it on and the tubes began spinning so fast that they flew out at an angle horizontal to the machine. After twenty minutes or so, the cells, being heavier than the fluid, sank to the bottom of each tube as an off-white pellet.
He turned off the machine, recovered the tubes, and, back in the sterile room, repeatedly blasted the pellet in each tube with medium, using a glass pipette with a cotton stopper and the power of his lungs. Eventually the cells came loose from one another. He sucked them up in the pipette, transferring them bit by bit into a big glass bottle. Moving quickly now so the cells wouldn’t stick, he poured the mix of cells and nutrient solution into several small glass bottles. He laid these carefully in the incubation room.
Some days later, after the cells had established themselves in the bottles, Hayflick handed a sample of them to Moorhead. This time the news that came back from his friend and colleague was good. Moorhead told him that the WI-38 cells’ chromosomes appeared entirely normal.
• • •
Hayflick knew that if he could freeze a large enough quantity of WI-38 cells, he could provide vaccine makers with enough cells to make vaccines for decades to come. How was this possible, if the cells were mortal and would, sooner or later, die in their bottles? Hayflick had shown how the math worked in the landmark 1961 paper. It was all due to the extraordinary power of exponential growth.
Suppose, Hayflick wrote in that paper, you began with just one small glass Blake bottle. It was rectangular and roughly pint-sized, its larger, flat side measuring a mere 5.5 inches by not quite 3 inches. Such a bottle held roughly ten million cells when those cells had grown to confluence on its floor—really, on its side, because the bottles lay on their flat sides while they incubated. If at this point you split these newly planted cells into two bottles, and split the bottles again when the floors of those two bottles were covered, yielding four bottles; and if you then kept splitting the bottles in this way when the cells reached confluence, until the original cell population had doubled fifty times—roughly the Hayflick limit—you would produce, he calculated, 1022 cells, or 10 sextillion cells. Knowing as he did that 14.2 billion wet cells weigh about an ounce, Hayflick also calculated that the cells in that one original bottle would therefore produce twenty-two million tons of cells.25
Admittedly, this was a theoretical maximum. Real life wasn’t nearly so neat. Sometimes Blake bottles got contaminated. Sometimes the am
pules in which he froze the cells cracked or, worse, exploded during thawing because liquid nitrogen had leaked into microscopic holes in their closures while they were frozen. (Hayflick took to wearing goggles when thawing ampules.) Sometimes cells got lost during shipping. And sometimes, frankly, they got thrown down the drain when there were leftovers after shipping them out to scientists.
On the other hand, there was room for a few accidents and a little waste when working with a potential ten sextillion cells—a number that’s so large it’s difficult to grasp. One way to think about it is this: the freshly harvested WI-38 cells covering the floor of just one of Hayflick’s pint-size Blake bottles, expanded until they have doubled roughly twenty times, would produce 87,000 times more vaccine than is made by a typical vaccine-making company, setting out today to make one year’s worth of a typical childhood vaccine that it will ship to more than forty countries.26
The point Hayflick was making with his calculation in the 1961 paper was that a sufficient supply of cells, frozen and thawed when needed, bit by bit, would produce all the cells that the world would need for the foreseeable future. Using his method, he wrote, “one could have cells available at any given time and in almost limitless numbers.”27
• • •
That summer, change was coming to America. As Hayflick cut the WI-38 lungs into minuscule pieces, the New Yorker published the first excerpt of Rachel Carson’s classic Silent Spring, launching the modern environmental movement. As the cells first reached confluence late in June, the Supreme Court ruled that voluntary prayer in public schools violated the constitutional separation of church and state. When President Kennedy, speaking at Philadelphia’s Independence Hall on a lovely, sunny Fourth of July, praised American democracy for encouraging dissent, three miles away the cells divided luxuriantly in ninety-six-degree heat. And as Hayflick set about creating a supply of frozen WI-38 cells that he intended to last for the foreseeable future, women’s constrained access to abortion landed in the headlines, in the person of an actress in Phoenix named Sherri Finkbine. Finkbine, a mother of four and a host on the children’s television show Romper Room, had taken the drug thalidomide to combat morning sickness early in her fifth pregnancy, unaware that it deformed fetuses. She could not get an abortion in Arizona, where state law allowed abortions only if the life of the mother was in danger.28 She ended up flying to Sweden to terminate her pregnancy, the press following her every step of the way.
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