But Hayflick didn’t get around to finding a lawyer; he was busy. By the summer of 1974 he had been at Stanford six years and had established himself as an important presence on the faculty. His groundbreaking 1961 paper with Moorhead, describing the Hayflick limit, was being cited by other scientists an average of sixty times a year—a huge number of citations compared with most papers—and Hayflick’s influence was growing commensurately. His lab in the parking lot behind the medical microbiology building buzzed with activity. He supervised graduate students, lab technicians, and postdocs, traveled extensively, and was the lead investigator on several NIH research grants and contracts that in the course of the years between 1968 and 1975 brought more than $2 million in NIH money to Stanford. (That’s nearly $10 million in 2016 dollars.) At home his youngest, Annie, was nearly nine years old, and Joel, the eldest, was preparing to become a freshman at Stanford.
In the midst of his dizzying schedule, in the late summer of 1974 an invitation came Hayflick’s way from the NIH. The new National Institute on Aging was being launched, responding to an explosion of interest in aging research. Would Hayflick consider being interviewed for the position of director?
• • •
Today ambitious biologists often found companies to commercialize their inventions. They rub shoulders with venture capitalists and dispense wisdom from their seats on companies’ scientific advisory boards. They are seen as paragons of success and are objects of envy, not scorn. Their universities applaud them and do all they can to enable their entrepreneurial efforts.
So it’s hard to appreciate what a radical departure it was in 1974 for Hayflick to form a company. In those days biology was pursued as an end in itself: for knowledge, for glory, perhaps, but not as a commercial enterprise. It had been so since at least 1923, when Frederick Banting and Charles Best, the Canadian inventors of the first “biotech” product—insulin extracted from animals—sold their patent rights to the Board of Governors of the University of Toronto, for $1 each, as a means of getting insulin made and out to the diabetics who needed it.9 In 1955, when the famous broadcast journalist Edward R. Murrow asked who owned the patent on the first vaccine against polio, its inventor, Jonas Salk, famously replied: “There is no patent. Could you patent the sun?”10
In 1953 the earnest author of a letter to Science captured this ethic and the expectations of biologists that accompanied it. The “true” scientist, the letter writer Frederick J. Hammett declared,
is not properly concerned with hours of work, wages, fame, or fortune. For him an adequate salary is one that provides decent living without frills or furbelows. No true scientist wants more, for possessions distract him from doing his beloved work.11
Very little in this attitude had changed when Hayflick founded Cell Associates. This did not deter him.
Hayflick launched the company, he says, not as a moneymaking venture but simply to get a tax advantage: being incorporated would lessen the amount of tax he had to pay on the money he was accumulating.12 (The $13,350 he had in hand at the time he incorporated would be more than $65,000 in 2016).13 Yet soon after founding the firm, Hayflick began to act like an entrepreneur. He ordered officials at London’s Medical Research Council, where he had sent one hundred ampules of the youngest WI-38 cells in 1962, to stop distributing them without first seeking his approval.14 And, departing from years of practice in which scientists, both commercial and academic, had come to him if they wanted WI-38 cells, Hayflick began to seek out customers in industry. With these firms he jettisoned any notion of recovering only his costs in preparing and shipping the cells. He began flat out selling them, at prices that brought in $47,543.38 in the fourteen months after he launched Cell Associates.15 (That’s $209,000 in 2016 dollars.)
In June 1974 he wrote to the French firm Institut Mérieux, which was using WI-38 cells to make Plotkin’s RA 27/3 rubella vaccine. He declared that it “has recently been decided that a supply agreement shall be made with manufacturers using WI-38 for research, development and production purposes.” In this letter Hayflick added that he didn’t want to set prices that would put WI-38 cells out of reach and asked the company for its view on what price would be reasonable.16 In August he wrote to the director of the Institute of Immunology and Virology in Zagreb, on Cell Associates letterhead. The Institute’s quiet but determined chief, Drago Ikić, had been the driving force behind Yugoslavia’s becoming the first country to license any vaccine made in WI-38 cells—a polio vaccine—in 1968. Hayflick now informed Ikić that young starter cultures of WI-38 could be supplied for $1,500 each. “We are currently supplying starter cultures of WI-38 at the ninth or tenth population doubling level (PDL) to several vaccine manufacturers of poliomyelitis,” he wrote in that letter.17 He later sent the Yugoslavian institute two starter cultures and collected $3,000.18
He approached New York–based Pfizer, the maker of the WI-38–propagated polio vaccine Diplovax, to ask if it would like to acquire a large stock of WI-38 cells; the company told him it wasn’t interested—perhaps because Lederle was in the process of chasing it out of the U.S. polio vaccine market.19 But another U.S. vaccine maker was highly interested. In mid-July of 1974, or soon after, Hilleman, the vaccine chief at Merck, called him, Hayflick says.
Hilleman was keenly interested in obtaining ample supplies of young WI-38 cells because, nine months earlier, Dorothy Horstmann had finally worn down the tough Montanan and persuaded him to drop the company’s HPV-77 duck-embryo rubella vaccine in favor of Plotkin’s RA 27/3 vaccine, produced using WI-38 cells. Hayflick remembers Hilleman telling him during that phone conversation that a Merck lawyer, Donald S. Brooks, had established that Hayflick owned the WI-38 cells. In addition, says Hayflick, Hilleman told him that Leon Jacobs, the associate director for collaborative research at the NIH, had affirmed to Merck that Hayflick owned the cells. (The NIH’s Jacobs would vehemently deny ever saying this.20Later Merck would tell NIH investigators that it did not proceed with the contract until Hayflick—not the company—attested that he owned the cells and that NIH concurred).21 Now Hilleman wanted to buy the youngest cells that Hayflick could provide.
Hayflick was impressed. “I don’t have to tell you how persuasive [Hilleman’s information] was,” he said in a 2013 interview. “I’m talking to a giant in the industry. A man who doesn’t want to risk his job as a vice president or besmirch the name of Merck. All that is critically important. So he certainly didn’t lie to me. Whether this [Merck] lawyer made a mistake in his interpretation is another question. Could he have? Certainly. But I acted on information I had.”22
On October 23, 1974, Hayflick executed a contract with Merck. In it he attested that Cell Associates had acquired ownership of all of the hundreds of young WI-38 ampules that Hayflick had taken from the basement of the Wistar Institute, and that previously he himself had had full right to and ownership of those ampules.23 The contract stated that, as president of Cell Associates, Hayflick agreed to consign to Merck one hundred ampules of WI-38 cells at the ninth population doubling level and fifty ampules of cells at the tenth. Each ampule contained millions of cells with dozens of doublings left in them. The company would be able to thaw and expand them, one ampule at a time, until Hilleman’s great-great-grandchildren were in their graves, and longer. For practical purposes the deal would assure Merck an unending supply of WI-38.
Under the contract Merck agreed to pay Cell Associates $5,000 for each ampule of cells at the ninth population doubling level and $2,500 for each ampule of cells at the tenth. Hayflick also granted Merck the right of first refusal on the sale of one hundred more of these young ampules. At the outset the contract would bring in $625,000. Fully executed, it would be worth $1 million—$4.8 million in 2016 dollars.
With his sales of the WI-38 cells to companies beginning in the spring of 1974, Hayflick crossed a line that would make it extremely hard for him to defend himself later. Had he simply continued to provide the cells to bio
logists and recover only the costs of preparation and shipping, he might have made a case that he was acting as a responsible steward, even if he was thumbing his nose at the 1968 decision by the NIH that the American Type Culture Collection should play this role and that the youngest cells should no longer be thawed and sent out. The arguments that he would later muster in his defense were true: that NIH officials became aware almost immediately, in 1968, that he had taken all the cells to Stanford and didn’t chase him down to recover them; that he had openly charged costs for shipping the cells—including to NIH scientists—for years, and the agency had uttered not a peep; and that he had reported distributing the cells “outside the contract” in his progress reports to Donald Murphy, the NIH project officer who supervised the contract under which he distributed the cells for free to researchers studying aging.24
But none of this would mitigate the public damage when juxtaposed with Hayflick’s collecting more than $47,000 from firms in the fourteen months that he sold the WI-38 cells through Cell Associates—or with his eye-popping contract with Merck worth up to $1 million. By amassing that kind of money for the cells and by negotiating the Merck contract, Hayflick made his case a political and personal disaster when the facts became public.
• • •
Ironically, just as Hayflick was defying the rules of behavior for biologists by launching Cell Associates, the first, hugely important, biotechnology patents—which would create some very wealthy academic scientists—were being planned a few hundred yards from Hayflick on the Stanford campus. There, at the medical school, an intense thirty-nine-year-old associate professor of medicine named Stanley Cohen was having his arm twisted by Niels Reimers, the forward-looking chief of Stanford’s young Office of Technology Licensing.
Stanford, like other universities in the late 1960s and early 1970s, was being forced to come to grips with the slowing growth of government funding for medical research after a quarter century of astonishing gains. Partly as a result, the university was becoming less passive about trying to commercialize inventions made by its scientists. Reimers, a former Stanford engineering major with experience in the electronics industry, was the face of its quest to do better.
In the spring of 1974 Reimers was trying urgently to get Cohen to agree to file a patent application. Cohen was the lead author on a landmark paper published in November 1973.25 He was proud of the paper and the huge contribution to biology that it was clearly going to make, launching a new technology so accessible that virtually any lab could use it. Cohen and his coauthors had succeeded in cutting and splicing genes from different biological sources into circular pieces of bacterial DNA called plasmids. By inserting the plasmids in bacteria, they could be made to pump out proteins coded for by those genes. Soon dubbed recombinant DNA technology, the invention would launch the biotechnology industry, leading to products like human insulin and clot-dissolving drugs for heart-attack patients.
But Cohen had not thought of patenting the gene-splicing invention that the paper described. Indeed, Reimers, Stanford’s tech-transfer boss, had learned of the exciting new paper only six months after its publication, because Stanford’s news director, Bob Beyers, sent him a copy of a New York Times article about it.26 The patent clock was ticking; any application needed to be filed by November 1974, that is, within a year of Cohen’s publication of the discovery.
Reimers recalled Cohen as a reluctant conscript who, when first approached by Reimers, told him he wasn’t interested in patenting the new technology. He saw his invention as something that was meant to go out to the research community broadly, not to become a commercial captive. Cohen, who was a physician as well as a scientist, acquiesced, Reimers remembered, only after Reimers argued that patent protection would entice companies that would license the technology and use it to develop drugs that otherwise would not be made—drugs like penicillin, whose commercial production had been delayed for eleven years for lack of patent protection.27In the end the patent application was filed just in time.
Cohen’s attitude was typical of the era.28 Biology was not thought of as a commercial venture, and most biologists looked askance on any colleague who moved in that direction. In 1976 Cohen’s equal partner in the revolutionary discovery learned this the hard way. Herbert Boyer, a biologist at the University of California at San Francisco, was the senior author on the recombinant DNA paper. After he partnered with a young venture capitalist named Robert Swanson and the duo used $1,000 of their own money to launch a company, Genentech, to exploit the new gene-splicing technology of which Boyer was a coinventor, he took tremendous heat from his academic colleagues.
Boyer recalled later that “the way the attacks went, I felt like I was just a criminal.”29
A good number of Hayflick’s colleagues, when they learned of his activities, reacted the same way. “In those days, in that environment, when you did research with government support, it was in the public domain. When it came out that Len was selling these cells, a lot of people were appalled,” said Cristofalo, Hayflick’s former Wistar colleague whom Koprowski had sent to Stanford to try to recover the cells from Hayflick.30
Hayflick, on the other hand, felt not the least bit like a criminal. He continued to see himself as providing a valuable service to colleagues—which he no doubt was doing—and to companies, in exchange for what now was clearly fair market value for the WI-38 cells. Vaccine-making firms, with their bottom-line focus, would not be handing him tens of thousands of dollars for tiny ampules of WI-38 if the cells were not precisely that valuable.
But there were major differences between Boyer’s enterprise and Hayflick’s. Boyer was an inventor on a patent—unlike the WI-38 cells, the Cohen-Boyer gene-splicing techniques could be patented because they were methods, not living things. What was more, Cohen and Boyer had assigned their rights as inventors to their universities, which would be the owners of any patents that issued. Whatever portion of the royalties might end up flowing to the men as individuals would be at their universities’ discretion and would be aboveboard gains for them under Stanford’s royalty-sharing policies. Hayflick, by contrast, was selling unpatented WI-38 cells that the NIH had paid him to develop under a contract that specified that title transferred to the government when the contract was up. His actions were rather akin to those of a horse breeder on staff at a stud farm—a breeder who is paid by a client to develop a world-class racehorse to sire more of the same. The breeder, after developing the prize stallion, moves cross-country with the animal and begins selling its offspring to wealthy racehorse owners, arguing that it is not clear who owns the valuable stud and saying that he will keep the proceeds of the sales until lawyers can figure that out.
• • •
On October 17, 1974, Hayflick spent the day in Bethesda, Maryland, at the invitation of the National Institutes of Health, in a preliminary series of discussions about the directorship of the new National Institute on Aging. He was briefed by the agency’s deputy director, Ronald Lamont-Havers, a jowly arthritis physician with black horn-rimmed glasses; chatted with staff in the Office of the NIH Director; then met over a lengthy brown-bag lunch with the search committee charged with finding a director for the new institute.31
Hayflick would later insist that, during his meeting with Lamont-Havers on that day, he raised the issue of his possession of the WI-38 cells and asked the NIH deputy director to assign a lawyer to determine who owned them.32 Lamont-Havers would just as vehemently insist that Hayflick made no such request.33 From the NIH’s point of view, it would emerge, Hayflick was anything but aboveboard with the agency about his sales of the cells to companies—until the most senior NIH officials learned of those sales, almost accidentally.
• • •
On Thursday, May 15, 1975, Donald Murphy, the midlevel NIH administrator who had launched and oversaw Hayflick’s ongoing contract to supply WI-38 cells for aging research, was attending a meeting at the Institute for Medical
Research, a cell repository in Camden, New Jersey. There he learned something that bothered him.34
Murphy was a former marine and a PhD marine biologist who grew up in Hawaii and had come to the NIH in 1967 as a grants administrator. Hayflick liked him and considered Murphy a friend as well as a colleague. Murphy had been communicating with Hayflick as the NIH prepared to open the National Institute on Aging on July 1, keeping him abreast of efforts to staff up the institute and sharing concerns that key positions shouldn’t be filled before a director—presumably Hayflick—was in place.35
Now, at the Camden meeting, Murphy was startled when someone told him that Hayflick was selling very young WI-38 cells to companies for $5,000 per ampule and somewhat older cells for $250. He contacted a commercial firm and learned that it had recently bought ampules of the slightly older cells from Hayflick at the latter price.36
Then Murphy called Hayflick and confirmed that what he was hearing was true—that Hayflick was selling the cells through Cell Associates. Soon he was on a hastily arranged conference call with Thomas Malone, the agency’s associate director for extramural research—and with Lamont-Havers, who by then was serving as the NIH’s acting director during a several-month gap between permanent directors. The matter was pressing, for the next day—Friday, May 16—Hayflick’s final round of interviews for the position of director of the National Institute on Aging was scheduled.37
The Vaccine Race Page 36