by Brian Deer
He didn’t say, for example, that, on Wakefield’s recommendation, he too had a deal with Barr. Only a week before the hearing, as I discover later, O’Leary had renamed a Dublin-registered company, “Unigenetics,” (of which Wakefield himself would become a director) to receive payments from the London class action. More than one hundred children, whose parents were suing over MMR, would be tested with his 7700 machine. And his company’s bill, picked up by the taxpayer, would be nearly eight hundred thousand British pounds.
Could these interests have impacted his possible independence? And those interests still weren’t the whole story. After gaining publicity, he would charge parents for tests, and his relationship with the man to his right, Wakefield, was yet more complicating than that. Company records, I find, from four months before the hearing, show O’Leary joining Immunospecifics as a shareholder. And the “Private and Confidential” draft prospectus for Carmel—which, until the head of medicine, Mark Pepys, intervened, had been planned for launch three months before the hearing—named a “Professor John O’Leary” as its fifth listed owner, with 11.1 percent of the stock.
“The company will have its technical base in the Department of Pathology, Coombe Women’s Hospital, Dublin,” the prospectus said, identifying the ABI Prism 7700, which O’Leary had praised on C-SPAN live, like he was selling committee members a Mercedes. “One of the founders of the business, Professor John O’Leary, has taken the concept of quantitative PCR much further.”
Ironically, Congressman Burton was a hawk on conflicts. And the discussion that had prompted the pathologist’s outburst had thrown this up as a topic. The committee’s ranking Democrat—Henry Waxman of California—had urged that O’Leary’s research be reviewed by federal agencies. But this suggestion was taken badly by the chair.
“We have been checking into all the financial records of the people at FDA, HHS, and CDC,” Burton hit back. “And we are finding that some of those people, even on the advisory panels, do have some possible financial conflicts.”
Evidently, he hadn’t checked the records of his witnesses. Yet the congressman looked to the tables. “Who funded your study, Dr. Wakefield?” he asked.
“We did,” Wakefield replied, after two seconds’ thought. “We have a small charitable contribution.”
“A charitable organization did, I see.”
“But we found it a little difficult to get funding.”
O’Leary wasn’t asked. Burton’s question was theater. Taylor acknowledged he was funded by the government.
I was surprised by O’Leary’s stress on his independence. Yet something he did tell the committee that morning was, to me, if not to them, more revealing. There appeared to be an anomaly, a contradiction in the science, grating on his associate’s evidence. Wakefield had said—as he often would—that Chadwick’s PCR was insufficiently sensitive. So it was, at least, logical that if O’Leary possessed a more sensitive gadget, it might find the virus. Made sense.
“TaqMan PCR is a thousand times more sensitive,” O’Leary said, “than standard solution phase.”
The machine’s manufacturer doesn’t support this, when I ask. But five times in his fifteen-minute talk to the committee, O’Leary also spoke of running “standard” PCR on the selfsame tissues from London. He even put up a slide with distinctive gel bands that were then staples of Chadwick-style work. And using this, he told Burton, “all children with autistic enterocolitis” also came up positive for measles.
“By solution phase PCR, by what we call fairly standard laboratory protocols,” he explained, “we can detect the measles virus in gut biopsies from these children, and the negative controls are appropriately negative.”
But, if that was right, I wonder, who needed the 7700? It might be nifty, but was it essential? And if standard, chopped liver, meat-and-potatoes PCR could detect measles genes in bowel samples from the children, why couldn’t Chadwick find it?
It was a riddle that nagged with the Crohn’s work, too, where Wakefield’s staining for proteins had been challenged. Why couldn’t the Japanese teams, at Akita and Hirosaki Universities, find the virus using PCR? And why, most pointedly, had there been a research letter in The Lancet on Saturday, February 28, 1998—just five pages back from the twelve-child paper—in which scientists at the British government’s flagship public health labs had likewise announced they’d failed?
O’Leary tested samples from Crohn’s patients, too, reporting measles in three out of four. “That’s an interesting biological fact,” he told Burton.
We’ll meet this pathologist again.
FIFTEEN
Letting Go
They’d had enough. Wakefield had to go. Only the means of his dispatch was undetermined. Within days of reports from Washington, DC, his managers, back at University College London, began debating the process to effect it.
Mark Pepys, the head of medicine, first got pertinent news at eight twenty-seven on the evening of April 5, 2000, thirteen hours ahead of Congressman Burton’s meeting in Rayburn Committee Room 2154. “Mark,” read the cover sheet of a three-page fax:
I attach the cast list for a Press Conference scheduled for 6 April before the Congress hearing. You will see that Andrew Wakefield will be taking part.
The source was David Salisbury, the civil servant and pediatrician who first encountered Wakefield after the brand withdrawals. He was assisting Democrats at the hearing. He’d now had more than seven years of the gastroenterologist, spent his working life dealing with a raging vaccine crisis, and knew that its architect, whom he’d grown to pity, had been asked to refrain from public statements.
Parents’ confidence in MMR was now sliding in Britain like a truck losing grip on the slope of an icy hill: a slow-slip skid to misfortune. From a peak of 91.8 percent before Newsnight’s package, the proportion of kids vaccinated with the three-in-one by the age of two had now slipped to 87.6. Outbreaks of disease crept inevitably closer as the cohort of susceptibles grew.
Wakefield had agreed to run a gold-standard study to endorse, or refute, his hypothesis. But he’d still not submitted any protocol to Pepys, and had ignored a reminder from the provost and president. “Three months have elapsed since I wrote to you,” Chris Llewellyn Smith had pointed out on March 16. “I would now ask you to send me, if possible within the next week, a progress report on the study proposed.”
Wakefield’s reply wasn’t a good omen. Any “further communications” on this issue, he wrote, should be made through his union, the Association of University Teachers.
Pepys was right. Wakefield wasn’t going to do it. He’d turn down a scientist’s gift of a lifetime.
So, now a staff file was pulled for a big-shouldered power-dresser by the name of Sarah Brant. She was University College London’s human resources director, leading a department of fifty at its Bloomsbury headquarters, and was assigned to the task of getting him out of the institution as quickly as possible, at the lowest cost, and with the least adverse publicity.
To Pepys, Wakefield was a waste of space. Not just a doctor without patients, but a teacher without students; not a scientist, but a zealot and opportunist. “He does no clinical work, and to my knowledge he does no teaching,” Pepys wrote to Brant and colleagues, in a memo I obtain. “My view is that his activities bring our institution into severe disrepute.”
Eyeballs scanned his more obvious research, and what they saw left managers’ jaws swinging. While newspapers lauded him like Galileo reborn, and mothers of children with developmental issues sometimes sobbed just to meet him, such papers that could be checked without access to his data (unlike the twelve-child Lancet report) were examined and told the tale.
Most technically complex was Kawashima et al. It was published in a low-rank journal, Digestive Diseases and Sciences, with Wakefield’s name following five Japanese physicians’, in the same month as the congressional committee hearings. First
-authored by the Tokyo pediatrician Hisashi Kawashima, and cited in the prospectus for Immunospecifics, it didn’t merely report measles genes in children’s blood but claimed that the sequences of As, Gs, Cs, and Ts were “consistent” with vaccine strain.
“Nine children with autistic enterocolitis—proved by ileocolonoscopy and histology—were all UK cases,” the paper said. “All had ileal lymphoid nodular hyperplasia and nonspecific colitis.”
Those patients reported positive included Child Two, whose case had been filed as the leading example in Richard Barr’s class action. And, to Wakefield’s supporters, the seven-page paper was explosively close to conclusive. “Dr Kawashima from Japan has confirmed that the virus found comes from the MMR vaccine,” was how a former USA Today columnist reported it. “Sounds like a smoking gun to me!”
But specialist scrutiny revealed peculiarities that a virologist could find with a wet finger. Not only did Kawashima use the same technology as Chadwick (contradicting the argument that it wasn’t sensitive enough), but the sequences were, indeed, smoking guns. First, they didn’t match any vaccine used in Britain. Second, they didn’t match themselves.
A measles virus genome is crammed with nearly sixteen thousand nucleotides, which (when converted from native RNA to DNA) could be run out in As, Gs, Cs, and Ts. To demonstrate that strains were consistent with vaccines, Kawashima had printed portions of those he found—sometimes including twice from the same patient. But when scientists compared the repeated sequences, they discovered that nucleotides changed. An A became a C, a G became a T, a T became a G, and so forth.
“Anomalies of this nature,” said an expert review, “are usually produced by cross-contamination.”
Two reports were also looked at that Wakefield had published with his sidekick, Scott Montgomery. This was the epidemiologist who not only coauthored the question-marked paper but joined him with the knights, professors, and doctors at the Royal College of Surgeons event. Like Kawashima et al., the texts and tables could be checked without data. And in these, once again, contamination was detected—but with origins that could only be human.
These texts were published across three columns of the Lancet’s letters section and five pages of an Israeli journal. Both contained a diagram (“Temporal trends for autism”) with two steep lines, from bottom left to top right, superimposing two graphs previously published by others on data from California and London. The texts claimed that the graphs showed how autism took off, ten years apart, “coinciding with the introduction of MMR.”
But the graphs were misaligned. MMR was licensed in the United States seventeen years before it was in Britain. Moreover, the California data was misrepresented. And, most importantly from the point of view of Wakefield’s managers, the graph from California had been doctored.
Like the question-marked paper, the diagram tried to make a point by comparing data collected by others. But the two rising lines only looked comparable because a word, “enrolled,” had been deleted from a caption for the California figures, and the surrounding space closed up. This transformed the graph from what it really was—the ages of children receiving support at state service centers (good news)—to the purported incidence of autism (bad news).
Number of [Enrolled] Persons with Autism
Who was responsible? It was impossible to say, but Wakefield continued to circulate it to parents, even after he’d been challenged over its truth.
By the time Wakefield’s staff file hit Brant’s desk in Bloomsbury, such anomalies were common-room banter. And later, another scientist, Tom MacDonald, professor of immunology and dean of research at Barts and the London School of Medicine, spotted another astonishing discrepancy. Two photographs, published in the American Journal of Gastroenterology, were labeled as comparing the “normal” small intestine at the terminal ileum of a purported MMR-affected child, with “severe” ileal lymphoid hyperplasia in another. But somebody had left date stamps visible on the images, revealing that the pictures were taken less than two minutes apart, and so could only have come from the same patient.
I admit I found Wakefield incapable of embarrassment. To me, he’d got no conscience. But his response to the university’s requests to do his job and prove claims that, by now, were terrorizing a generation, went beyond such errors (or whatever they were) into a blank refusal to answer the question with the gold-standard study—claiming this would infringe his “academic freedom.”
Months passed. Then came a last straw: a blunt confirmation, in September 2000, that he wouldn’t mount the project he’d agreed to. He wrote to Llewellyn Smith:
It is the unanimous decision of my collaborators and co-workers that it is only appropriate that we define our research objectives, we enact the studies as appropriately reviewed and approved, and we decide as and when we deem the work suitable for submission for peer review.
Two months later, he defied the request that he stop making public statements and appeared on the CBS network’s 60 Minutes program: his biggest chance yet for publicity.
Five weeks after that, Brant swiveled to her screen and wrote a paper of her own: three pages:
Mr Andrew Wakefield—mutual termination of employment
A plan was constructed to ensure that the university’s senior managers were on board to weather the inevitable storm. The Mail on Sunday’s Lorraine Fraser had now moved to the Sunday Telegraph, and she was sure to spin the story his way. So on the document’s third page was a list of seven names, seven job titles, with seven dotted lines: as if for a failed state dictator’s execution.
From the president and provost to the vice-provost (administration) and the director of planning and management accounts, between November 2000 and January 2001, Brant’s document went back and forth between Hampstead and Bloomsbury, until every dotted line was signed.
The plan was final. But execution would take forever. Such was job security in academia at the time that it would take nearly another year to complete. External lawyers were hired. Accountants went to work examining his spending. He’d be asked to explain long absences in the United States. And even his letterhead—the printed paper he wrote on—was studied for irregular claims.
Wakefield’s correspondence had long provoked mirth. Now it was eyed as evidence. A typical doctor or scientist, like almost any office staff, would sign work letters above a short designation. Simon Murch, for example, who scoped most of the Lancet kids, used “Dr. Simon Murch, Senior Lecturer.” But Wakefield communicated—even within the school—with a grandiose panoply of self.
He was only a mid-rank lab researcher, after all. But, not content with the dignity of this station in life, he’d fashioned a personal letterhead. After the name of the school, the university, the department, and the “Centre for Gastroenterology,” he added:
Inflammatory Bowel Disease Study Group
Director A. J. Wakefield MB BS, FRCS
Fair enough, I suppose. Ink on paper. But, as if this wasn’t enough to announce him to recipients, below his signature were typed thirty-two further words, that, if he needed them at all, would have filled five lines, but were configured to occupy a more impressive six lines, like scrambled eggs on an admiral’s cap.
A J Wakefield FRCS
Reader in Experimental Gastroenterology in the
Departments of Medicine and Histopathology
Hon. Consultant in Experimental Gastroenterology to the Royal Free
Hampstead NHS Trust
Director, Inflammatory Bowel Disease Study Group
Murch could have padded his dignity too. But here were shades of Wakefield delusion. Brant wrote to him pointing out that he left the histopathology department in March 1998, and so should stop describing himself thus. He’d not been entitled to “FRCS” since July 1996, when, according to the Royal College of Surgeons, he’d resigned by withholding his fees. The “Hon. Consultant” was a courtesy title, of li
ttle significance outside the building. And the last line (repeated from the top of the page) had been dealt with during his bid for a professorship, when the school secretary, Bryan Blatch, had told him:
The Inflammatory Bowel Disease Study Group is not a department of the School, and I have no recollection of the title Director being conferred upon you.
Low self-esteem? Anything but. All the signs said Wakefield thought he was special.
And on it went, into 2001, when he revealed how special that was. Instead of agreeing to prove his career-defining claims, he coauthored another paper with his favored sidekick that was so wildly wrong that when I came to study it—pulling the source materials from the British Library’s vaults—I found anomalies line by line.
It was nominally published in February 2001, in a short-lived journal called Adverse Drug Reactions and Toxicological Reviews, with a circulation of just 350. Wakefield had it press-released the month before, however, through a not-for-profit entity called Visceral that he’d set up to raise money outside the medical school.
Fraser, at the Telegraph, was primed in advance.
Shame on officials who say MMR is safe
As was another acolyte, at the Daily Mail:
MMR: A marvel or a menace?
But Britain’s worried parents didn’t have a clue about the junk that lay behind such headlines. The new paper appeared to be an independent review of science, running to nineteen pages. Coauthored by Montgomery (who, legal records indicate, would be paid nearly £90,000 to support Barr’s lawsuit), it was grandly titled “Measles, Mumps, Rubella Vaccine: Through A Glass, Darkly.”
Indeed.
The official position is that MMR vaccine is safe; this paper examines the evidence.
Except that it didn’t. It was a campaigning pamphlet, framed to make a case. Claiming to review prelicensing safety studies—conducted between the 1960s and the 1980s—the authors made it look like researchers had long known that combining three vaccines was risky.