by Brian Deer
So this was the man, the grandfather of the crisis, at whose feet sat the doctor without patients. Fudenberg tells me that he manufactured his cure on what he called “a sheet, about three cells wide,” which he rolled out on his kitchen table.
“And where does that come from?”
“From my bone marrow.”
“From your own, personal, bone marrow?”
“Yeah.”
Wakefield’s secret science proposed a modified approach: turning the transfer factor into pills. And where the American’s product went straight from donors to patients, Immunospecifics planned to interpose animals. According to the patent supplied to Tarhan, the extract would be made by injecting measles into mice, from which lymphocytes would be isolated, grown with human cells, and injected into pregnant goats.
The goats’ colostrum, their first milk, would then be collected, freeze-dried, and, I speculate, sold under the “Royal Free” brand. It was, as one expert (a professor of immunology at the University of Cambridge) explained later, an evolution from Fudenberg’s “merely eccentric” to Wakefield’s “totally bizarre.”
Tarhan, nevertheless, was presented with a prospectus giving a detailed share-out of the spoils. The “initial equity position,” as it described the planned ownership, was set out in the following order: Sleat, Wakefield, Pounder, Korda, Fudenberg (who says he declined the invitation), the medical school, and a “charitable trust.”
But why, one might ask (I know that I did), spend time and money on a cartoon company, unless you’re as crazy as a Spartanburg coot? Then I remembered the lesson of an investigation I’d done in the late 1990s into the “world’s first AIDS vaccine,” AidsVax. A clique of ex-staffers from the US Centers for Disease Control and Prevention, in Atlanta, Georgia, had been inspired, I think, by Mel Brooks’s film The Producers, premised on the idea that you could make more money from a Broadway flop than you might from a successful musical. The CDC guys got $12.6 million in federal grants for their company (named VaxGen), a big tank of gunk in South San Francisco, floated stock on the NASDAQ, and retired.
Here was the beauty of biotech start-ups, although I can’t speak to anyone’s intentions. If Immunospecifics bombed—as you’d have to think was possible—the owners might nevertheless pay themselves. On top of their share of the initial equity (which they might sell to the faithful before the bubble exploded), the prospectus listed Wakefield drawing £33,000 a year as part-time research director (while still working for Barr and the medical school); Sleat, full time, receiving twice that amount; Korda getting £20,000 as executive chairman; and Pounder £7,500 a year.
Boosted by the Royal Free, The Lancet, and the media, if they could raise the initial capital, they should do just fine. Good money, win or lose. “Few VCs [venture capitalists] have the technical knowledge to understand what the patent was about,” one source who knew about this project speculates to me in an email. “And even if they did realise this, many would consider it was worthwhile to invest anyway. They would put money in, hype the company on an AIM [alternative investment market] based on the huge public attention, and run.”
TWELVE
Asked and Answered
Three weeks after the meeting with Cengiz Tarhan, somebody nearly beat me to unmasking Wakefield’s twelve-child study for the project it really was. Her name was Anne Ferguson, aged fifty-seven: scientist, clinician, wife and mother, professor of gastroenterology at Scotland’s University of Edinburgh, a fellow of no fewer than five royal colleges and societies, and a front-rank expert on bowel disease.
This was Monday, March 23, 1998 (twenty-five days after the press conference in the Atrium) at a daylong scientific meeting. She was there. So was he. And she asked him a question so simple, and basic, that had he answered her truthfully, openly, and completely—behavior expected at a scientific meeting—the public alarm over MMR and autism might have ended, there and then.
The event was organized by the Medical Research Council, expressly to consider Wakefield’s work. Contrary to his later claims of sinister plots, he’d been accorded respect and tolerance of a kind that few enjoyed in twentieth-century Britain. Including Ferguson, Wakefield, and a CDC staffer who’d flown in from Atlanta, fifty-seven people were present: immunologists, virologists, epidemiologists, gastroenterologists, pediatricians, statisticians, and more. Twenty were professors (including six men knighted to the glorious title “Professor Sir”).
The location oozed with privilege and grandeur: the neoclassical headquarters of England’s Royal College of Surgeons—like the gateway to Heathfield, only bigger. Rising five stories and finished in Portland limestone, with six fluted columns across a giant Ionic portico, it overlooked the grass and trees of Lincoln’s Inn Fields: the biggest garden square in London.
Their eyes met that morning at an open rectangle of tables, laid out across a wood-paneled room. She: a tousle-haired Scot, a strong, solid woman, who’d climbed in the Himalayas, played international basketball, and published three hundred papers and book chapters. He: a trainee gut surgeon turned charismatic crusader, whose name would live forever in medical history—albeit not in the way he planned. Behind them, observers crowded a second rank of chairs. A mechanical projector fired slides.
After introductions and coffee, Wakefield took the spotlight. Now attention was where he liked it. “He was flying high,” remembers David Salisbury, the Department of Health civil servant and pediatrician, who, seven years before, received the demand for money after two vaccine brands were withdrawn.
“It is a great pleasure to be here,” Wakefield began, screening the first of more than forty transparencies summing up his work on Crohn’s. “I hope that you will at least try to reserve judgment, right to the very end, because the data do look interesting.”
The gathering heard him out. People took notes. But when he finished speaking, the virologists and immunologists battered him like a southern fried chicken. How could it be, they wondered, that he claimed to find the virus using the protein-targeting immunohistochemistry (which nobody present doubted was “relatively insensitive”), and yet highly sensitive molecular amplification, targeting nucleotides, had so often drawn a blank?
The day was chaired by an urbane professor of medical microbiology, Sir John Pattison, editor of Principles and Practice of Clinical Virology and A Practical Guide to Clinical Virology. “Where is that genome which produces the specific protein,” he asked, posing the enigma most succinctly, “if you cannot find the nucleic acid?”
For the knights, professors, and doctors around the tables, the popcorn moment came quickly. Wakefield’s best evidence that measles caused Crohn’s—and which he previously claimed “confirmed” his J Med Virol findings—was contained in a manuscript that he’d supplied in advance. It was the latest in a series, going back several years, staining for proteins with special gold-labeled antibodies, which, when viewed through an electron microscope, he said, found “persistent infection” with the virus.
But, as Ferguson sat listening, David Goldblatt, a Great Ormond Street immunologist, projected a slide of the manufacturer’s instructions for the antibodies Wakefield had used. Critically, they specified a set of four negative controls—for example, using a different version of the antibody in parallel—to guard against false-positive reactions.
“I do not want to give you my opinion,” Goldblatt said. “I would rather just show you what the company from whom they bought the gold conjugates say about negative controls.”
Wakefield was nailed. The slide spoke for itself. Likewise, the study he supplied. Of the manufacturer’s four required negative controls, Goldblatt could find only one in Wakefield’s work. “These are simple to perform,” Goldblatt recited from the instructions, as if reading aloud from a cake-mix recipe, “and should always be included.”
The moment was tense, especially in light of the findings from Connecticut, which had suggested that another aspect of Wakef
ield’s methods was picking up a cross-reaction.
Then, after a half-hour lunch, the proceedings changed direction, with a talk by Wakefield’s sidekick, Scott Montgomery. He was then thirty-six, a sometimes-untidy-looking epidemiologist, who’d been one of the four authors of the question-marked paper that was the peg for the Newsnight report.
Montgomery’s contribution covered the efforts to link the virus (both in vaccines and natural infection) with the later development of Crohn’s. But his cookie crumbled badly as the statisticians present chewed it. And, by the time he finished screening his selection of transparencies, he was admitting that his data didn’t merely not support the question-marked paper but actually suggested that the shots reported in that study were protective against the disease.
“Our work and other people’s work,” Montgomery conceded, “does not support that monovalent measles vaccination, at a typical age, is a risk.”
Does not support? But wasn’t the claim that measles vaccines were implicated in Crohn’s disease fundamental to all that followed?
Three speakers declared themselves “confused.”
Looking back on the transcript of that day’s discussions—112 pages, sixty-five thousand words—it’s hard for me not to feel disgust. Here was Wakefield and Montgomery, who, three years earlier, with the cheap-thrills Lancet, a money-grubbing medical school, and a box-of-rocks reporter from the BBC’s Newsnight, dumped on the public that question-marked paper—putting Jackie Fletcher on television, leading to the phone call from Ms. Two to Hampstead—and now it was a steaming heap.
Like, nobody suspected that comparing incomparables would generate junk? I think not.
But Wakefield, as ever, remained calm and unflustered. “If we were born all-knowing we would not be sitting round this table,” he said, shedding, like snakeskin, the paper that first brought him to public attention. “Clearly, hypotheses evolve.”
Ferguson’s expertise was so broad and deep that she made two dozen interventions that day. But none hit the nail like one that she asked before afternoon tea was served. Now the twelve-child paper was the topic of discussion, and she wondered the same as I would, years later.
Where did he get the children?
This was a critical issue. And yet nobody had asked it, as if manners wouldn’t permit the inquiry. At face value, the paper reported on routine patients—a write-up from the casebook of a pediatric bowel clinic where parents had repeatedly made the same shocking claim: of an association between autism and the MMR shot, with behavioral symptoms coming on within days.
“I am going to be forthright,” Ferguson began. “Since it looks as if nobody else is going to raise the issue of bias in generating this series of cases.”
Selection bias. Publishing rules sought to catch that in formal instructions to researchers. In a ponderously titled document, Uniform Requirements for Manuscripts Submitted to Biomedical Journals (adopted by more than five hundred publications, including The Lancet), what authors must disclose was stipulated. The code’s fifth edition, in force at the time, said a paper’s opening “abstract” section should state the “selection of study subjects,” with a later “methods” section spelling it out.
Describe your selection of the observational or experimental subjects (patients or laboratory animals, including controls) clearly.
Ferguson had a personal reason to wonder. She’d appeared in the Newsnight package. She’d seen herself saying there were no correlations between the introduction of measles vaccine and “any shift in the pattern of Crohn’s disease.” She’d seen a group of parents performing stiffly for the camera. And she’d seen Jackie Fletcher, the woman in scarlet, who founded that group called JABS.
“Maybe that the time scale I have got, and the facts I have got are not correct, but at least my perception is as follows,” she addressed Wakefield at the meeting. “That, about 1994, your group became concerned about measles vaccine as a hazard, and that coincided with the organization JABS being either created, or supported, or sponsored, or some interest in the idea.”
She was digging the right ditch. JABS was founded in January 1994, with Fletcher’s determination to sue. Her son had been vaccinated in November 1992, just two months after the publicity over the brand withdrawals. And after she shared Newsnight’s platform with Wakefield, she referred clients and contacts to him.
Ferguson continued, with regard to the Royal Free. “I understood that there was a lot of publicity on the telly and newspapers, on the internet, suggesting that, if someone had a child with autism and bowel symptoms, that this was the center in the world to find out about it. I mean, I think, is that not correct?”
It was correct. But it was incomplete. Not only was there JABS, there was the lawyer Richard Barr inviting clients to seek contact with Wakefield. And the result—unspotted before my investigation—was a cohort of complainants who’d gone to the hospital, with nearly all of them intent on suing. Ferguson was gnawing near the heart of the paper that, unknown to her, was contrived with a lawyer, who paid the first author at hourly rates, and was sponsored by the taxpayer, through the Legal Aid Board, to make a case against MMR.
Such were these features that John Walker-Smith (who refused to attend the Atrium press conference) became concerned over the project’s integrity. “It is clear that the legal involvement by nearly all the parents will have an effect on the study as they have a vested interest,” he wrote to Wakefield before the last of the twelve kids was scoped.
I obtain a copy of that letter (headed “Enterocolitis and Regressive Autism”), and I publish extracts in the Sunday Times, including the Australian’s most pertinent observation:
Never before in my career have I been confronted by litigant parents of research work in progress. I think this makes our work difficult, especially publication and presentation.
Yup: especially publication and presentation.
Ferguson knew nothing of that private correspondence. And she wasn’t a journalist, or a lawyer. So instead of pushing harder on a door that should have opened, her question segued into clinical observations, like ulcers, swollen glands, and sore ears.
But Wakefield responded. At last, a reply. After the day’s embarrassments over histopathology and hypotheses, Ferguson had impugned without proof.
“Thank you for being forthright,” he said, reframing her concerns in terms she hadn’t used. “I imagine you are suggesting we are a sort of dumping ground for disaffected parents? No, we are not.”
She hadn’t said anything about “dumping grounds” or “disaffected parents.” But, having denied his own charge, Wakefield doubled down with an assertion he surely knew was untrue.
“And, indeed, these parents came to us de nouveau,” he said, “without any connection through any other organization.”
Had JABS’s founder been present, she might have said otherwise. With the family from California a notable exception, those crucial parents—at the foundation of the health crisis—nearly all had links to her group.
Could Wakefield have forgotten Walker-Smith’s letter? Or the case of Child Four, with the “most compelling” history, whose mother had written to him, citing Fletcher and litigation in the opening paragraph of her flower-patterned letter? Or Ms. Twelve, the mother who met him at a JABS meeting before she brought her son to Hampstead? Or, another case I learned of, where Kirsten Limb, Barr’s “scientist” wrote to the Royal Free, pressing for the admission of a client.
I’ve plenty more. But life’s too short. I’ve no doubt that Wakefield knew.
In the wood-paneled room, however, he saw off Ferguson. She simply didn’t have enough facts.
“Latterly,” he continued, “parents have heard about our work—through the media, or through other organizations—and have come to us.”
Latterly? Surely what he meant was from the outset. Right from Child Two, his “sentinel case,” they
were coordinated, organized, schemed.
Go no further than Ms. Two herself, referred to him by Fletcher after the Newsnight broadcast. He sent her to Barts Hospital, where Walker-Smith saw her son and discounted inflammatory bowel disease. But then six months later—from a report of the mother’s account—she joined Barr’s books for the proposed class action. Then four months after that, at Wakefield’s suggestion, the professor invited her to bring her son to Hampstead.
At the Royal College tables, Wakefield offered a final thought. He didn’t want any persisting confusion. “All patients that we have reviewed so far,” he told the gathering, “have come to us through their general practitioners, or pediatricians, by the standard route.”
The standard route? It went like this: on learning of a promising child for his research, he’d phone the mother, or ask the mother to phone him, and then would call her general practitioner. This conduct, in itself, was all but unheard of. National Health Service consultants didn’t solicit. But in those calls he might speculate that the kid (whom he’d never seen) might suffer from a potentially appalling inflammatory bowel disease, and offer the Royal Free’s help.
That would do it. Imagine the parents’ worry. A rubber-stamp referral was assured.
Who in that wood-paneled room would have guessed that in doctors’ offices scattered across Britain, lay medical records that, thanks to an old-fashioned newspaper investigation, would one day be exposed to the light?
Regarding a seven-year-old boy, sixty miles northwest of Hampstead:
Dr Wakefield, consultant gastroenterologist, Royal Free rang and gave a v lengthy and convincing case for [Child Five] to be referred to Professor John Walker-Smith.
For a four-year-old boy, sixty miles south of the hospital:
Dr Wakefield—Royal Free. To discuss association measles + Autism + inflammatory bowel disease . . . If we feel relevant can refer for treatment to Professor Walker at the Royal Free for investigation.
