The Vaccine Race

by Meredith Wadman

  Soon after the transfer, John Shannon, who headed the ATCC’s cell culture department, drafted a memo to the cell bank’s director, Dick Donovick. Shannon reported that the federal scientists had delivered to the ATCC 103 ampules of young WI-38 cells. Of these, 46 were ninth-generation cells and 57 were the youngest, eighth-passage cells. These 57 were what remained of the 375 eighth-passage ampules that Hayflick had moved to Stanford from the Wistar in 1968. Since their arrival at the ATCC, Shannon added, two of the eighth-passage ampules had exploded. The rest of the cells, he wrote, “are properly inventoried, racked on canes, and stored in a separate liquid nitrogen refrigerator (MVE Model VPS 3500).” They are kept, he added, “under daily surveillance.”69

  CHAPTER TWENTY-TWO

  Rocky Passage

  Stanford and Oakland, California, 1976–78

  Because of the government’s decade long cold-shouldering of WI-38’s, it is hard not to feel sympathy with Hayflick’s sense of irony and outrage that the same government now claims the cells to be its own precious property. Nor is it strange to hear him say that “I felt, and I think I am justified in feeling, that these cells were like my children.”

  —Nicholas Wade, Science, April 9, 19761

  On Sunday, March 28, 1976, the following headline appeared on the front page of the New York Times: INVESTIGATOR SAYS SCIENTIST SOLD CELL SPECIMENS OWNED BY U.S.2

  Reporters for the newspaper and several other publications had used the Freedom of Information Act (FOIA) to obtain the fourteen-page, single-spaced report that James Schriver and his deputies completed late in January 1976.3

  Hayflick had been given until April 1 to rebut the Schriver report and its conclusions, but when in mid-March reporters invoked FOIA to access the document—and a court challenge from Hayflick failed to stop the agency from doing so—the NIH released it without his rebuttal.4

  The contents, and the media coverage of them, were damning.

  Hayflick, Schriver reported, had “sold cell cultures of human diploid cell strains, the property of the United States Government.” He had charged most of the costs associated with the sales to NIH research agreements and deposited most of the receipts in his private bank account and later in the bank account of Cell Associates, a company in which he and his wife were the sole shareholders. A total of $67,482.33—just over 1 percent of it interest earnings—had accumulated since 1968. (This is about $286,000 in 2016 dollars.)

  The report recommended that the government recover the money and that it consider banning Hayflick from participating in NIH grants and contracts.

  There was much else in the Schriver report. A good chunk of it documented the investigators’ fruitless efforts to square Hayflick’s records of the WI-38 cells he had thawed, expanded, and shipped with the number of WI-38 ampules actually on hand in the lab. Hayflick calculated that he had brought 375 eighth-passage ampules with him to Stanford; Schriver arrived at essentially the same figure: 379. There any agreement ended. Schriver calculated that Hayflick could not account for at least 207 of the ampules. Hayflick contended that all of these ampules either were sent to the Medical Research Council in the UK, were lost or exploded at the Wistar, were cracked or exploded during transfer from the Wistar to Stanford, or were found to be contaminated or dead in 1968 and 1969.

  Schriver was not convinced, and his frustration oozes from the pages of the report.

  “Almost every situation concerning the accountability for these cells has produced unexplainable differences,” he wrote. “No record made available to us fully accounts for the 8th passage ampules.”

  Nor, Schriver wrote, had Hayflick stewarded the cells responsibly. They were shipped out at lower passage levels than necessary, when expanding the cells to higher levels and refreezing those that were in excess of current demands would have preserved the supply of low-passage ampules. (Hayflick would argue convincingly later that neither scientists nor companies wanted middle-aged cells; they didn’t live long enough to be useful.)5

  The report also rang alarm bells about “a very high level of contamination” in the WI-38 ampules. It said that Hayflick had since 1968 used antibiotics to treat a score of eighth-passage ampules that were discovered upon thawing to be contaminated with bacteria. These were then shipped, after antibiotic treatment, to scientists studying aging and to paying customers without notifying them, or the NIH, of the contamination and the “cleaning up” of the cells with antibiotics. (Hayflick later vigorously disputed that such cells were ever knowingly shipped to companies.)6

  Contamination was not uncommon in cell culture generally, and not surprising either, given the circumstances under which the ampules were created on that midsummer day in 1962. And contamination and antibiotic treatment didn’t spoil the cells for use in research. For vaccine makers and regulators, however, it was a matter of dispute whether “cleaned-up” cells should be used for vaccine making. Virtually all companies treated their cells with antibiotics at some point in the vaccine-making process, but many or all began with sterile cells never treated with antibiotics. The idea was to use antibiotics in such cells to prevent bacterial contamination, not to treat it. All the same, at an NIH conference one year later, at least one speaker argued that cleaned-up cells could be used for vaccine making without risk.7

  The Schriver report lamented that Hayflick had not notified the DBS (later the FDA) of the contamination “of a cell line which was in the process of being studied for use in preparing vaccines for human use.” From Hayflick’s point of view, this was rich. Why would it have made any sense for him to notify of contamination an agency that, during most of the years he was shipping the cells, was dead set against their use for vaccine making? Later he would write of both the former DBS chief Roderick Murray and Harry Meyer, the man who replaced him in 1972: “Neither cared about our work, and both fought our efforts to have [WI-38] cells used for vaccine preparation.”8

  Arguably the most damaging section of the report, though, detailed Hayflick’s sales of the cells to companies between March 1974 and the Montreal meeting in June 1975—including the inking of the million-dollar Merck contract.

  When the Schriver report became public, Hayflick released a one-page statement to reporters. It read, in part:

  I am shocked and grieved that NIH has released a report which is erroneous and incomplete, without affording me the opportunity to complete the written rebuttal which they requested be filed by April 1, 1976. I had been assured by NIH that I would be permitted to submit my rebuttal before NIH completed its determination of the facts and consequences of those facts. . . . I absolutely deny any wrongdoing . . . and I urge my scientific colleagues around the world who have long relied upon my integrity and that of my work to regard with great caution the statements in the report.

  In view of the fact that I have been denied due process by the NIH, I am seeking due process in the courts. I have on March 25, 1976, filed suit in the U.S. District Court in San Francisco against the Department of Health, Education and Welfare and the NIH. . . . I am confident that I will be totally vindicated by the judicial process.9

  The appearance of Schriver’s findings on the front page of the New York Times was difficult enough for an acutely image-conscious man who had so often appeared in that newspaper’s pages in a glowing light. But the truly devastating article—the one that addressed his own community and the one that Hayflick still speaks of bitterly forty years later—appeared in Science magazine under the headline HAYFLICK’S TRAGEDY: THE RISE AND FALL OF A HUMAN CELL LINE.10

  It was written by Washington-based staff reporter Nicholas Wade, who had rushed to California, interviewed Stanford officials and Hayflick (with his lawyers present), and compiled a 3,500-word article in five exhausting days.11 The article delved into every aspect of the Schriver report.

  Wade pointed out that NIH officials had not exactly avidly pursued the cells they were now calling a “national resource” in th
e pages of the New York Times.12After making the failed trip to Philadelphia to collect the cells in the winter of 1968, several months before Hayflick left the Wistar, Wade reported, Boone, then the NIH project officer, called Hayflick at Stanford in the fall of 1968 to demand the cells’ transfer to the ATCC. Hayflick agreed to do so but didn’t follow through, Schriver reported. (Hayflick told Schriver that he had no memory of ever having such a conversation with Boone.)13

  After that, “things sort of disintegrated,” NIH associate director Leon Jacobs conceded to Wade. “We are not completely faultless in this.”

  Wade wrote that Hayflick’s not-yet-public rebuttal might totally exonerate him and quoted Hayflick’s press statement urging “my scientific colleagues . . . to regard with great caution the statements in the [Schriver] report.”

  But Wade’s reporting made it clear that the rebuttal was going to need to surmount some high hurdles.

  The facts in the Science story were made worse by Hayflick’s efforts to explain that he had supplied all of the WI-38 cells to companies, and could continue to do so, by using only the ten original eighth-passage ampules that he was permitted to keep for himself when he left the Wistar.

  Wade described Hayflick’s explanation that he could fulfill the Merck contract with far fewer ampules than Schriver believed by growing the cells in larger-than-usual laboratory bottles. In essence, he meant that he could put the roughly two million cells from one eighth-passage ampule in a bottle with a surface area large enough to allow the population to double several times over—say, to 25 million cells, he told Schriver—before it reached confluence.14 Then the cells could be placed into what Hayflick estimated would be fifteen ampules for Merck. According to Hayflick, the resulting cells would still be, by scientific convention, ninth-population-doubling-level cells, because they had been “passed” into new bottles just nine times.

  “It is hard to find anyone who agrees with Hayflick’s calculations,” Wade wrote, quoting unnamed experts who called Hayflick’s reasoning “terribly feeble” and said it “would be laughed out of court.” Merck’s Hilleman, whom Wade also interviewed, was less vituperative, but his message was the same. He said simply that one would expect to derive one hundred ninth-passage ampules from fifty eighth-passage ampules.

  Wade also reported that it appeared that supplies of pristine, low-passage WI-38 ampules were alarmingly small. The NIH had recovered from Hayflick’s lab a total of about one hundred eighth- and ninth-passage ampules. But the ATCC, now in possession of the ampules, had opened nine of them and discovered that six of these were contaminated with bacteria. If all of the one hundred or so ampules at the cell repository were contaminated in equal proportion, there were in fact far fewer ampules suitable for vaccine making than anyone had believed.

  “The real tragedy for Hayflick is not what the NIH inquiry or Stanford has done to him but what he has apparently done to the future of WI-38’s,” Wade concluded. “It now appears that there are sufficient stocks only for the next several years.”

  The article ended by quoting the NIH’s Jacobs saying, duplicitously, that he doubted that the agency would choose to bar Hayflick from obtaining NIH grants, as Schriver recommended, and that “in the long run . . . things will straighten out for this guy.”

  But its most powerful quote undoubtedly came from Hayflick’s old Wistar colleague Stanley Plotkin. Wade wrote: “According to Plotkin, many people warned [Hayflick] about the sales, but he was not open to any kind of remonstrance. ‘I think that in the really classical Greek sense it was a tragedy, because it is a man who at the height of his powers brought about his own downfall,’ Plotkin says.”15

  • • •

  By the time the New York Times and Science articles appeared, the Schriver report was not news in the Hayflick family. Hayflick’s son, Joel, studying that winter at Stanford’s campus at the country estate of Cliveden in England, picked up the Stanford Daily of March 3, 1976, to discover the banner headline PROF IN ALLEGED FUND MISUSE. The article reported that Hayflick had resigned the previous week and that “Hayflick allegedly used Stanford laboratories to produce, store and sell cell cultures in his own commercial enterprises.”16

  “The university was concerned that its laboratories were inappropriately used in the performance of a contract to store, produce, and distribute a strain of human cells, some of which Hayflick sold on his own behalf,” a Stanford press release announced on February 27, the day that Hayflick’s resignation became public.

  Hayflick, in a press release composed by the university and quoted by the Daily, maintained that he had abided by Stanford’s rules governing contracting. He told the Daily that “it was all done in good conscience” and that he resigned voluntarily, on principle, because “the university impugned my motives.”

  Schwartz, the medical school counsel whose first-ever words to Hayflick had been “You better get a lawyer,” responded in the Daily: “Our position as to motives is that the funds were improperly deposited in his personal account.”

  Schwartz would also, with a nod from the NIH, pass the Schriver report on to the district attorney—the local criminal prosecutor in Santa Clara county.17 The DA ended up electing not to pursue the case, although not before telephoning Fadlo Mousalam, the lawyer whom Hayflick had hired the previous summer, and causing Hayflick to sweat.18

  Hayflick had forgone, with his unforced resignation, a chance for an adjudication of his case before the Stanford faculty’s advisory board, essentially a jury of his peers.19 The new, highly capable lawyer whom he hired several weeks later—the young William Fenwick, who would go on to become a Silicon Valley superlawyer—rued that decision mightily.20

  On the Stanford faculty there was a conspicuous silence from many quarters and some vocal support. He remembers that Henry Kaplan, a powerful Stanford Medical School radiologist, lobbied both the medical school dean, Clayton Rich, and Stanford president Richard Lyman on his behalf, to no avail. Kaplan looked at him at one point and, worried about his heart, sent him to a cardiologist colleague for a checkup. (Hayflick was pronounced fit.)

  On the other side of the country, Harry Schwartz and Noel Buterbaugh, both senior executives at the laboratory supplier Microbiological Associates and old friends, hired Hayflick as a consultant and began flying him out to Maryland regularly to advise them on cell-culture technologies.

  Zhores Medvedev, a Soviet dissident and scientist, wrote a scathing letter to Science. (In 1972 Hayflick had organized a group that faced down Soviet authorities and forced them to release Medvedev when he was arrested at an aging conference in Kiev.) The “tragedy” alluded to in Science’s headline, Medvedev wrote to the magazine, “lies in the surprisingly tendentious approach of Science” to the Hayflick matter—and in the fact “that an outstanding scientist can be forced to resign his professorship at a university without discussion of his case by his colleagues.”21

  Others simmered angrily out of public view. Merck’s Hilleman recalled decades later: “I was asked to be a principal witness against him and I said that if there was an intent to convict him, I would make a campaign on my part that two top-level government officials would spend time in jail with him.” He added: “He should have been celebrated as a scientific hero instead of being persecuted.”22

  As in many controversies in which one side is more passionately motivated than the other, Hayflick’s backers, Hilleman’s circumspection notwithstanding, were outspoken, while his detractors—those who were “appalled,” as Hayflick’s former Wistar colleague Cristofalo put it years later—were largely silent. The fall of a colleague, however much they disagreed with his actions, was not pretty to behold, and it’s likely that many were not motivated to add to his humiliation by slinging arrows publicly.

  One indication of their feelings, however, is apparent in this letter from Albert Sabin, the polio vaccine inventor who had recommended Hayflick for the job at Stanford. Asked several
years later to sign a letter to Science in support of Hayflick, Sabin wrote to the letter’s organizer:

  I consider myself a friend of Len Hayflick, but I am not in sympathy with the type of activity, especially his association for profit with Cell Associates, Inc., which led to the dispute with the NIH. I hope very much that you have not used and will not use my name in the letter that you propose to have published in Science and elsewhere.

  Sincerely yours,

  Albert B. Sabin, M.D.23

  • • •

  Several weeks after his resignation, Hayflick hired the sharp young Palo Alto intellectual property lawyer Fenwick, whose testimony before legislators had helped shape a new law, the U.S. Privacy Act of 1974. Fenwick was then with a Palo Alto firm called Davis, Stafford, Kellman and Fenwick. Today he is an emeritus partner at Fenwick & West, a highly influential law firm with more than three hundred lawyers that is a Silicon Valley institution. The firm has represented companies including Facebook, Apple, and Google. Fenwick himself first represented the nineteen-year-old Steve Jobs when he was founding Apple Computer.

  Fenwick recalled in a 2012 interview that he was convinced that Hayflick genuinely believed he had done nothing wrong.24 He would not have taken on the case with very little prospect of compensation at his then-$75-an-hour rate had he not believed in the man, he said. Fenwick was ready to contest the NIH’s claim to ownership of the cells. He also thought he could make a strong case that the NIH had violated the new Privacy Act by releasing the Schriver report.

  There ensued a long legal battle in which Hayflick, represented by Fenwick, sued the U.S. government for ownership of every WI-38 ampule taken from his lab by the NIH, and any progeny they might produce. He also claimed the accrued $67,000, as well as damages for defamation.25 The government in turn countersued for recovery of the money.26

  The legal proceedings would stretch to five years. In the meantime, in March 1976, Hayflick suddenly had no job, no lab, and a consuming bevy of legal troubles. He had never been clinically depressed, but he fell into a deep depression. Not a big man to begin with, he lost ten or fifteen pounds. For some reason, he could eat Big Macs when nothing else appealed. He became a regular at a McDonald’s on El Camino Real, the commercial thoroughfare that runs along the eastern edge of the Stanford campus.