by Brian Deer
Pepys’s specialty gave him insight into Wakefield’s methodologies. He was a leader in the field of amyloidosis: a group of mysterious, rare conditions that could damage practically any organ through the buildup of rogue protein fibers. In the 1980s, he’d invented a diagnostic for the problems. And, in the following decade, he devised a screening system to identify potential therapies. So, while his quarry was elusive, Pepys cast his net wide in the clinical, cellular, and molecular.
He also drove red Jaguars, wasn’t easily schmoozed, and arrived with a predisposition. “They made me an unrefusable offer,” he tells me of the negotiations that brought him to Hampstead. “And I said, ‘Here are twenty-five conditions under which I will come, and I want the dean to sign at numbers one to twenty-five—twenty-five signatures—for these things that I want.’ And one of those was Wakefield out of the department when I take office. Because I knew he was a wanker and a fraud.”
Here was a twist at the turn of the century that the doctor without patients couldn’t control. The doctrine of “tenure” made dismissal tough, but Pepys wasn’t only a formidable scientist. He was also an adept office politician. And when Wakefield asked permission to accept two consultancies—one with a drug company, Johnson & Johnson, and the other with a biotech start-up called Carmel—it didn’t take the new head of medicine long to find out that “Carmel” was the name of Wakefield’s wife.
“He said, ‘But we’ve proved it, and we’ve got this Nature paper,’ ” Pepys tells me of their first meeting, in his office at Hampstead. “I said, ‘Stop, what Nature paper? Is it accepted?’ ‘No.’ ‘Have you submitted it?’ He said, ‘No.’ I said, ‘Thank God for that. What were you proposing to submit?’ He said, ‘We’ve proved it, because we’ve got ten cases of this, and seven cases of that’ . . . And I said, ‘Do you not understand statistics 101, Mr. Wakefield?’ ”
Now it was Pepys who made the unrefusable offer. Wakefield could choose between paid leave of absence, to work for a year with his biotech business, or conduct a gold-standard test of his hypothesis. With University College London funding, help, and facilities, he could mount a molecular study—with definitive genetic sequencing—that would endorse, or refute, his ideas about measles virus. Once and for all. Without doubt. He should include at least 150 of the children he said he’d recruited, and his methods should be mirrored at two external sites, to ensure accuracy and publishing speed.
You would think any scientist would be delighted by such an offer: with time, support, and money. But Wakefield balked. He didn’t seem keen. Response from him came there none.
Meanwhile, Pepys learned of an extraordinary negotiation in which the school’s commercial arm, Freemedic, sought options to profit should the business venture succeed, but to deny any involvement if it didn’t. “They may choose never to exercise such options,” Cengiz Tarhan, the finance officer, wrote to Wakefield in November 1999. “Therefore neither Freemedic nor the School are in any way involved with Carmel until such options are formally exercised and shares are taken up.”
So Pepys bypassed the school and had Wakefield summoned downtown and, in administrative parlance, upstairs. They traveled, with Pounder, to Bloomsbury, three miles south, where, at the university’s headquarters, guarded by stone lions, a soft-spoken silver fox and theoretical physicist repeated Pepys’s offer. His name was Chris Llewellyn Smith, formerly director-general of the CERN particle collider in Geneva, Switzerland, also a fellow of the Royal Society, and the occupant of an office about half the size of a football field, as the college’s provost and president.
Seated at a hefty conference table, Llewellyn Smith asked Wakefield to conduct the research that frightened young families deserved. He also asked him to stop making public statements until he’d published the results of his findings. Not only would the university support the project, on those terms, but, if he agreed, it would give him his patents for the tests, vaccines, and products to exploit as he pleased through Carmel.
“We urge you not to publish prematurely observations that you may have or be making in this field,” Llewellyn Smith wrote to him afterward, in a two-page letter that Wakefield received on Monday, December 13. “Good scientific practice now demands that you and others seek to confirm or refute, reliably and above all reproducibly, the possible causal relationships between MMR vaccination and autism / ‘autistic enterocolitis’ / inflammatory bowel disease that you have postulated.”
And that’s how things stood at the concrete castle as the twentieth century slipped toward closure. As fears of Y2K did the rounds in table talk, lights burned late in the head of medicine’s office as Pepys mulled the likely response. In Pepys’s opinion, Wakefield was a fantasist. He was unlikely to agree to proper science.
But then, just eleven days before the first light of January, Wakefield fired back a response. “Further to our meeting and the Provost’s letter,” it said, in part, “I am prepared to comply with the request.”
FOURTEEN
On Capitol Hill
John O’Leary had the gift of the gab. In room 2154 of the Rayburn House Office Building, 350 yards from the US Capitol, he seemed to speak with such authority—independent authority—it felt like game, set, and match for Wakefield.
“I can confirm,” O’Leary declared, in a soft Irish lilt, “that his hypothesis is correct.”
As viewed from the front of the high-ceilinged committee room, O’Leary sat toward the left of a narrow strip of tables, which were draped in white linen, as if for dinner. Bald, but for a monkish dark fringe behind his scalp, and obese beyond the threshold of clinical concern, he bulged in a navy suit, white shirt, and gray tie. He peered through wire-framed glasses.
He was aged thirty-six, an associate professor of histopathology, and spoke toward an ornately carved two-deck platform, from which a dozen or so lawmakers gazed back. Here was a defining moment in the emerging controversy outside Britain over the safety of immunization.
“Ninety-six percent of the children’s biopsies that he sent to my laboratory,” O’Leary continued, “children with autistic enterocolitis, harbor measles virus genomes.”
This was Thursday, April 6, 2000. In the morning. Nearly four years before my first report. O’Leary had been invited to give evidence as an expert. His testimony was the day’s big event. Ms. Two had flown in to watch proceedings from a side room, and Lorraine Fraser, the Mail on Sunday medical correspondent, monitored the proceedings from her office in London for a major write-up that weekend:
Exclusive: The damning evidence that the medical establishment has chosen to ignore
O’Leary had come to the tables twenty minutes before, after nearly two hours of listening. First were statements from the politicians at the front, then a panel of six parents assembled along the tables: all to address the House Committee on Government Reform, with Congressman Dan Burton in the chair.
Burton was a Republican, representing a patch of the state of Indiana, and convened that hearing—an intense five hours—in pursuit of a personal quest. He was convinced that his much-loved grandson, Christian, was a victim of vaccine damage.
“I can’t believe that that’s just a coincidence that the shot is given,” Burton had said, as the parents yielded the tables to a medical panel of O’Leary and five others, “and within just a matter of a few days, instead of being the normal child that we played with, and talked, and everything else, he was running around banging his head against the wall, flailing his arms.”
Burton named the next six witnesses. Then they stood, shoulder to shoulder, right arms raised, to take the oath on the accuracy and completeness of their evidence. The congressman quizzed them at the rapid-patter speed of TV warnings about drug side effects. “Do you solemnly swear to tell the whole truth and nothing but the truth, so help you God?”
O’Leary confirmed that he did.
Behind him sat well-dressed women and men: a half dozen rows
, mostly the day’s contributors. And, to his right, sat Wakefield, importing his crusade to his next big market: the USA. With a press conference that morning alongside anti-vaccine campaigners, and live coverage by the public affairs network C-SPAN, today was his chance to plant his message, and lay the groundwork for his business schemes.
I’d rarely seen him so sharply turned out as he appeared, far left, at those tables. His hair, trimmed and thinned, spoke of money well spent, and his complexion bore a smoothness that, for a man of forty-three, might suggest a light touch of cosmetics. He wore a formal black suit with the faintest of pinstripes, black shirt, and rectangle-pattern tie.
He’d spoken before O’Leary: talking through slides screened on a monitor mounted high on a wall. “Nothing in this testimony should be construed as anti-vaccine,” he began. “I advocate the safest vaccination strategies.”
Then he cruised through his evidence for thirteen minutes—effortless, articulate, elegant, plausible—like a hang glider riding a thermal. “Autistic enterocolitis” was a “real syndrome,” he said, with a “remarkably consistent” bowel disease and “regression.” He said the swollen glands were “the important image.” He screened before-and-after pictures of the blond-haired Child Two. He spoke of opioid peptides “impacting on the brain,” made a distinction between regressive and classical autism, and gave the lawmakers a summary of the first sixty children to pass through Malcolm Ward.
“The great majority had autism,” he said, fingering a pencil. “But there was a spectrum of neuropsychiatric problem, including Asperger’s syndrome, and attention deficit disorder.”
Given the evolution of developmental diagnoses, this was a worthy contrast to highlight. “Asperger Syndrome,” as it was then called in Europe under the World Health Organization’s International Classification of Diseases—or “Asperger’s Disorder” in the American Psychiatric Society’s manual—took a less troubling slot than autism on the spectrum.
But central to the case he set out that morning was, as ever, his big idea. Measles. And here, two and a half minutes before O’Leary began, he gave the hearing what resembled a confession. “We had failed completely to identify this virus by molecular amplification technology,” he admitted—meaning Nick Chadwick’s PCR tests, promised to the Legal Aid Board at the start of the deal with Richard Barr.
The technology of which he spoke, the polymerase chain reaction, was an immensely powerful tool. Long a lab workhorse throughout the scientific world, it split the double helix of DNA to allow the specific amplification of any target sequence. In quick, repeated cycles of heating and cooling in a test tube, the double-stranded DNA came apart, unzipped, into something like broken-runged ladders. Then a miracle enzyme danced the snapped rungs, joining on fresh nucleotides, replacing what was missing, to create two double strands of identical DNA where previously there had only been one.
Wakefield’s buddy, measles, was coded in RNA, and required a prior step (“reverse transcription”) to convert it to DNA. But with PCR methods, it could be doubled just the same: exponentially increasing until it was present in such numbers that sequences of the famed building blocks of life—adenine, thymine, cytosine, and guanine—were sufficient to be detected, read, and checked again with nucleotide sequencing techniques.
TGACTCG TTCCAGCCAT CAATCATTAG TCATAAAATT AATGCCCAAT . . .
But the young scientist, Chadwick, had found nothing in the samples, whether from autistic or Crohn’s disease patients. And although Wakefield had supervised him (even coauthoring a paper validating the test), the former surgeon reached a different conclusion. The lab’s failure, he argued, was in the technology itself. The PCR wasn’t sensitive enough. He’d reported measles proteins using microscopic staining, and insisted that the molecular method was unable to find the genome (which determines the proteins’ component amino acids, without which the virus didn’t exist).
“In my laboratory we had a reaction that was sensitive to about ten thousand copies,” he told the committee, before O’Leary’s turn came, referring to virions one would expect by the million. “Anything less we couldn’t find.”
Now for the Irishman, seated to Wakefield’s left. They’d known each other, and worked together, for two years. On the advice of Robert Sleat, the venture capitalist and Lancet parent, the doctor without patients had flown to New York—billing the legal board for the cost of his trip—to propose a research collaboration. At the time, O’Leary was a visiting professor at Cornell University, but had since returned to Ireland to supervise a lab at the Coombe Women’s Hospital, Dublin.
“May I inform you that I am a pathologist and a molecular biologist,” O’Leary proclaimed in oddly stilted vocabulary. “These studies were undertaken following an approach made to me by Dr. Andrew Wakefield, who has just submitted independent testimony.”
Then he explained his success where Chadwick had failed, peppering his talk with technobabble, and speaking of a novel piece of kit. His lab had a revolutionary detection system, he said. He called it “TaqMan PCR.”
“I have worked in this technology for the last six years,” he explained, glancing back and forth between Burton and the video monitor. “It’s approximately a thousand times more sensitive.”
Unlike what he called “standard” or “solution phase” methods (with which researchers like Chadwick relied on reactions in conventional test tubes), what he called “TaqMan”—more usefully referred to by its supporting equipment, the ABI Prism 7700—was automated, with bells and whistles. Laser beams scanned trays in a closed machine and, when amplifying the target during heating and cooling, it didn’t merely give a signal if a gene segment was present but, by counting the cycles before this signal was elicited, it also quantified how much was there.
With this neat device—about the size and general finish of a big Xerox copier—O’Leary said he’d tested gut samples from forty children. They included twenty-five kids with “autistic enterocolitis,” and fifteen developmentally “normal” patients as negative controls for comparison.
Now came the big moment in room 2154. O’Leary gave headline results. He’d found measles gene sequences in inflammatory bowel disease, he said, and, especially, in Wakefield’s enterocolitis.
“Twenty-four out of twenty-five children—that’s ninety-six percent of the children’s biopsies that he sent to my laboratory, blinded—children with autistic enterocolitis—harbor measles virus genomes,” he declared. “One of fifteen—six point six percent—of control children harbored measles virus genome. And I think it doesn’t take great statistical analysis to work out that there is a significant difference between twenty-four out of twenty-five, and one out of fifteen. Next slide.”
It was like the bloody glove scene from the trial of O. J. Simpson. The very air seemed to drain from the room. “In terms of the association that Andrew Wakefield alluded to, I can confirm that his hypothesis is correct.”
Here was vindication. And O’Leary had more: to showcase the independence of his data. He had slides of black material, spidery, looking evil, which he explained was the virus in tissue. He said his lab had “strict anti-contamination measures” to “outrule” false-positive results. And he confirmed his discoveries, he said, with “fluorescent-based sequencing”—outputting the strings of As, Gs, Cs, and Ts—to definitively fingerprint the bug.
In fifteen minutes, he stressed sequencing seven times. He called it the “gold standard” confirmation. In a written report to the committee, he even identified his equipment: an ABI Prism 310 capillary sequencer—a different piece of kit to the 7700—which checked results, nucleotide by nucleotide.
“We can sequence measles virus isolates from these children,” he said, as a brown-haired woman in a blue dress, behind him, twisted her head from side to side. “And, of course, we can sequence it, and we can say that this is measles virus RNA present in the biopsies of these children.”
What mo
re needed saying? Wakefield was endorsed. The professor appeared to have the proof. As Fraser reported in the Mail on Sunday that weekend:
The potential importance of Professor O’Leary’s results will not be lost on solicitors for some 200 children—large numbers of them autistic—who are already suing the makers of MMR.
But not everyone in room 2154 was convinced. Four places to O’Leary’s left at the white-clothed tables, sat another professor, who’d also flown from Europe to address the committee on vaccines. His name was Brent Taylor: a white-haired, stubble-cheeked, New Zealand–born pediatrician, who not only worked at the Royal Free medical school, but had published on MMR in The Lancet. He’d looked for, and didn’t find, any “step-up” in autism cases corresponding with the triple shot’s introduction.
O’Leary’s results were as yet unpublished, and Taylor was one of a handful of observers in the room who didn’t assume they were correct. “This information does have to be verified by an independent laboratory,” he told Burton, when his turn came to contribute to the discussion.
The implication provoked fury from the Irish pathologist, who demanded permission to speak again. “What I present is evidence, direct evidence,” he stormed. “It was done at a separate laboratory from Dr. Wakefield’s. If Professor Taylor has a beef with me, he should say that. But my work is completely independent. I stand over it. I’ve come here to tell the truth. There is nothing for me to be gained in not telling the truth.”
His resentment was understandable. He was confident of his findings. Certainly I can’t challenge them. But in his oath to the committee, he swore to tell the whole truth. And I wonder if he protested too much.