The Doctor Who Fooled the World Page 3

  The Perth pair, however, were fêted by The Lancet: the world’s number two general medical journal. Founded in London in 1823, by a rabble-rousing surgeon-politician named Thomas Wakley, it was proud of a legacy of contentious propositions and wasn’t shy of Warren and Marshall’s. It had delivered their big break in June 1984: a four-page paper in its most prestigious research slot, underneath the main dateline near the front.

  Unidentified Curved Bacilli in the Stomach of Patients with Gastritis and Peptic Ulceration

  Wakefield had watched Warren and Marshall for years. Like him, they asked big questions. And only weeks after settling into a small second-floor office, next to the Royal Free’s gruesome pathology museum, he thumbed through The Lancet’s Christmas double-issue and feasted on more from the Aussies. They now had a five-pager, with seven coauthors, again in the journal’s top slot.

  Heathfield . . . the Guinness Moment . . . Warren and Marshall . . . thus, the beginnings of the Wakefield story. Years later, all manner of armchair commentators would look for overarching explanations in media, sociology, or a mystical zeitgeist for why millions became exercised over vaccines. But there were only real people, and specific facts, in a cascade of cause and effect.

  Next came reaction—only eleven months later—when, inspired by the Australians, a Wakefield-led team seized six pages in the journal’s top position. Using electron microscopes to photograph resin casts of archived samples cut from Crohn’s patients’ intestines, they reported inflammation, blockages, and tissue death in blood vessels supplying the gut wall.

  Six pages in the number two general medical journal. Wakefield walked on water. Publishing was the first of two metrics of his performance, and The Lancet could transform a career. More important to the Royal Free’s dean and managers (and shaping their behavior in what was to come) was its potential for their profile and accounts. At the time, the medical school competed in a national “Research Assessment Exercise.” Using a scale, mainly based on success in high-impact journals, activities at institutions of higher education were ranked in steps, from 5 down to 1, to decide the share-out of hundreds of millions in government grants. University College London, three miles south, was assessed with straight 5s in two vital areas. The Hampstead school: 2 and 3.

  Those pages on Crohn’s were therefore money in the bank. But Wakefield needed to name that virus. Then the dean, a virologist by the name of Arie Zuckerman (whose role in the scandal would have to be seen to be believed), might join him for drinks at Buckingham Palace, after one or both of them knelt before Her Majesty the Queen.

  Some researchers stumble upon their signature achievement. Others test everything that moves. But Mr. Wakefield—still styled and self-described as a surgeon—employed a technique so simple for the next step on his path that his lack of science training proved a boon. As he later explained to the journalist Jeremy Laurance, who quoted this line in a nine-hundred–word feature:

  I sat down with two volumes of a virology textbook, and worked through it.

  Simple as that.

  When I took up the story, I mimicked Wakefield’s approach. The book was Fields Virology. Two red-and-silver tomes, each weighing half a brick. An encyclopedia of viruses. Second edition. It grouped these microbes into eighteen families, with members profiled alphabetically, across double-columned pages: histories, clinical features, epidemiology, and genetics. A who’s who and what’s what of what he sought.

  But Laurance had the quotes. And we should be grateful for his diligence in capturing them for posterity. “I got to measles virus,” Wakefield told him, “and it described how it gets into the gut, causing ulcers and inflammation. You could have been reading an account of Crohn’s disease.”

  Measles virus. In the Morbillivirus genus of the paramyxovirus family of single-stranded RNA bugs. The thirty-two-page chapter pointed to origins, possibly, in ancient Rome or China, evolving from the cattle plague rinderpest. History’s pioneering Greek doctors Hippocrates and Galen never noted it, and the symptoms—fever, cough, rash, and telltale white “Koplik spots” in the mouth—seemed to take hold with the evolution of cities, as a roughly ten-day illness of childhood.

  “In the mucus membranes of the mouth, the necrotic epithelial cells of the Koplik spot slough, leaving a tiny shallow ulcer,” noted the passage that quickened Wakefield’s pulse.

  Lesions equivalent to Koplik spots have been found during the prodrome and first day of the rash on mucosal surfaces throughout the body, including the conjunctivae; the oropharynx; the nasopharynx; the lining of the larynx, trachea, bronchi and bronchioles; the entire length of the gastrointestinal tract; and the vagina.

  The entire length of the GI tract. That’s just how Crohn’s could be. Although most typically found in the ileum (the part of the small intestine that’s furthest from the stomach), the condition may manifest from mouth to anus. And lesions equivalent to Koplik spots. So . . . the nasty ulceration of the inflammatory bowel disease was like measles of the gut.

  Eureka.

  So here was the first great Wakefield hypothesis: measles virus caused Crohn’s disease. And now, announcing formation of what he called the “Inflammatory Bowel Disease Study Group” at Hampstead, he began drawing in others with technical skills, whom he led onto the field of battle, like in rugby.

  “I thought he was a man who had a good idea, or what seemed like a good idea at the time,” says Philip Minor, then chief of virology at the British government’s National Institute of Biological Standards and Control, on the northern fringe of London. “And he was looking round for scientists to help him.”

  Wakefield knew that his path wouldn’t be easy. Naysayers preened like parakeets. Some pointed out that his photographs were mere snapshots and didn’t prove inflammation began outside the gut, rather than inside, as they assumed.

  Whispers went round that maybe the ex–bowel surgeon just didn’t get the science. “He gave a seminar in my department,” recalls one senior academic over lunch. “And there were a lot of people in my department, basic scientists, very, very smart, whose whole life was working on blood vessels. And he came and gave this talk—and this was the first time I heard him talk real science. And I sat there, and it was a sort of hour-long seminar, and after about three sentences, I had no idea what this guy was talking about.”

  You just heard a voice from the medical establishment: an establishment that had been wrong before. “Everybody knows the stomach is sterile,” was how the Australian Robin Warren would recall of the naysayers later, when in Stockholm collecting his medal. Such was gastric acidity, experts assured him, that the bugs couldn’t survive the environment. And even if they could, somebody else would have noticed. “Why has not anyone described them before?”

  Repelled by such complacency, Wakefield was encouraged. Like the Aussies, he’d keep his nerve. Still barely recognized among the school’s staff of seven hundred, he coauthored papers in the journals Gastroenterology and Gut in which his team continued probing blood vessels. Then, in April 1993, he broke big again in the Journal of Medical Virology. Known to its readers as J Med Virol, it was edited by Zuckerman, the medical school’s dean.

  “These studies suggest that persistence of measles virus in intestinal tissues is a common event,” Wakefield summarized, amid nine dense pages of text and images, “and a consistent feature of tissues affected by Crohn’s disease.”

  In his career résumé, that would be paper twenty-seven (with the one that would make and break his career numbered eighty), adding a feather to his professional cap. J Med Virol wasn’t great for impact. But with a team of six associates, whose names followed his, he reported impressive results. Probing for evidence of the virus in surgically removed Crohn’s tissues, they used three methods (all laboratory standards), each of which came up trumps. One scored positive in thirteen of fifteen patients, another likewise in nine of nine, and the third in ten out of ten.
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  One technique—known as “immunohistochemistry”—looked for signs of proteins from which the virus is built: coded, as measles is, in RNA. Another—called “in situ hybridization”—hunted for a segment of the RNA itself, deep within the bug’s genetic core. Neither was foolproof. But his third was box office: using an electron microscope, magnifying specimens up to eighty-five thousand times, his team appeared to photograph his quarry.

  There was measles—or there it was reported—smudgy shadows in a moonscape of craters, blobs, swirls, and spots, which he described in a 260-word caption. He noted objects “consistent with densely packed viral nucleocapsids,” with “virus particles” and “infected” cells. He gazed on the face of his destiny.

  The second metric of his performance was the money he raised: whether in grants from the government’s Medical Research Council, from charities in the field of inflammatory bowel diseases, or, more often, from the pharmaceutical industry. In Toronto he was funded by the Wellcome Trust: at the time the grant-giving arm of a British-American drugs empire, founded by a Wisconsin-born salesman, Henry Wellcome. But after an extension of that award through 1993, his begging bowl was out for more.

  Economics were also under review at home. He and Carmel had moved to a bigger west London house: in a short terraced street of bay windows and brick, beside a rail line from Waterloo station. They now paid out as parents of two young boys, with the second, Samuel Ryder Wakefield, named after his great grandfather (Edward Matthews’s father), a St. Mary’s graduate of 1896.

  Much of Wakefield’s work was routine, even boring, compared with the excitement to come. But the clock was ticking. He needed results. And the naysayers pecked at his heels. Not only was he listed on the medical school’s budgets, but critics pointed out that while his hypothesis proposed that Crohn’s was caused by measles and, in developed countries at least, Crohn’s diagnoses were rising, cases of measles had fallen through the floor with the advent of immunization.

  A lesser-driven man might have slapped his forehead and spent three weeks in a bar. But the way Wakefield told it (although I’d later bring a different light) was that this apparent contradiction inspired him. Measles vaccines contained weakened, but functional, measles virus. Therefore, he reasoned, these might also cause Crohn’s and so explain its rising prevalence.

  Proving that hypothesis would definitely need money. And he knew he’d the skill to get it. Time and again, I heard of this quality: a remarkable attribute that, to be frank, nearly everyone lacks. “Charisma . . . charisma . . .” Like a drumbeat through his life: an astounding psychological power.

  Now he applied it to pharmaceutical executives, along with charities and not-for-profits. He lured Upjohn of Michigan, Searle of Illinois, the Swiss giant Hoffmann-La Roche, and the London-based Glaxo (later GlaxoSmithKline, or GSK) to lob more than coins into his hat.

  Such support would sit uneasily with his claims, years later, that he was a victim of Big Pharma scheming. And, yet more irony, the next link in the chain of specific facts that led him toward what became his war on vaccines was in part funded by Merck of Rahway, New Jersey, the world’s number one vaccine manufacturer. “It was kind of basic work,” a retired executive shares the joke with me. “But he did take money from Merck.”

  Now switching from virology to epidemiology, his team followed up two unrelated British studies executed in the 1950s and 1960s. One was a child health survey before measles vaccines were introduced, and the other an early trial of the shots. By writing to participants (at least those who could be traced), Wakefield concluded that Crohn’s was three times more common in those who’d been immunized compared with those who weren’t.

  His target for publication was, again, The Lancet, with its cherished crowd-pleasing inclinations. As a general medical journal, it sought to appeal to readers from disparate specialties with big-brush, sometimes frankly tabloid, topics that everyone would remember from medical school. So, in April 1995, it printed his study in a three-page paper, with four authors listed, including the Royal Free’s professor of gastroenterology, Roy Pounder, and a Wakefield sidekick named Scott Montgomery, who were both to feature in supporting roles as hagiography would give way to disgrace.

  The Lancet took chances. But it guarded its name with specially commissioned winks to the wise. For specialist readers, who might otherwise complain, it often printed extra articles—effectively editorials—to pull the sting of extravagant claims. And, in this case, two scientists at the US Food and Drug Administration were invited to file a “commentary.”

  Wakefield, they pointed out, had compared incomparables: like trying to match plums against mangoes. “There were fundamental differences in the ways in which the study cohorts were recruited and interviewed,” they wrote of the 1950s and 1960s sources, “and in how their constituents were ultimately classified according to exposure and disease.”

  To be fair, the team’s paper owned up to shortcomings. It was speculative. Nothing was proved. Measles “may” persist in gut tissue, they said. Early exposure “may” be a risk. People with Crohn’s “may” have an altered immunity. And so weak was any link with immunizations that their report’s title was flagged with a question mark.

  Is measles vaccination a risk factor for inflammatory bowel disease?

  The caveats were glaring. They leapt from the page and provoked a few titters of amusement. Some branded the title as a case of “Hinchliffe’s rule” (known in journalism as “Betteridge’s law of headlines”): that when a title is a question that can be answered yes or no, the correct answer is invariably no.

  Nevertheless, Wakefield’s sights were now set on vaccines—not merely on measles found wild in nature—as the cause of Crohn’s disease.

  But where—he wondered—could he find the evidence to prove such a big idea?

  THREE

  Quests Collide

  The way Wakefield would tell it, his adventures in autism began with a phone call from a mother.

  Narrowly framed, it’s true. This was May 1995. Friday, May 19, to be specific. In his second-floor office, a telephone rang. A lady recounted the story of her six-year-old son. And nothing would ever be the same.

  She was also the mother who triggered my investigation. So, you might say, she brought us together. I’ll call her “Ms. Two,” and her son “Child Two”: anonymized with the number he’d be given in the research project for which Wakefield would never be forgotten. But nothing about this mother and boy was secondary. They were emphatically, irrevocably, first. The then doctor would describe them as the “biggest influence” on his life. Child Two was his “sentinel case.”

  The boy was born in late July 1988—full-term, the due date—weighing 8 lb. 10 oz. (3.9 kg)—with not a hint of anything wrong. His mother’s pregnancy was uneventful. She needed no drugs in labor. And four or five minutes after a snag-free delivery, her new baby scored a perfect 10 on the APGAR scale (Appearance, Pulse, Grimace, Activity, and Respiration), against which the condition of newborns was logged.

  Carried home from the hospital in the county of Cambridgeshire, northeast of London, Child Two was all set for the best life could bring to a middle-class twentieth-century English family. His father was a computer specialist, employed in engineering, and Ms. Two an information manager and business analyst for a top travel agency in the capital.

  Thus began infancy as good as it gets. The boy’s gaze sharpened. He rolled, babbled, and laughed. He began to crawl, then cruise, gripping furniture. He pointed, shaped sounds—“mama . . . dada”—and, one amazing day, rose to his feet unsupported and took his first steps, before tumbling. In this child was a reason, an ultimate fulfillment, a crowning existential achievement.

  Second year: looking good. Blond hair. Blue eyes. He splashed toys in the bath, pulled a toy dog with a waggy tail, and built towers of bricks to match the best.

  But, sadly, horribly, it wasn’t to las
t. His parents’ desperate quest would begin.

  Medical records pinned the change after the middle of that year—a few months before his second birthday. He became “withdrawn and inaccessible,” with “nightly screaming bouts” and, at some point, episodes of “head banging.” You’d be surprised how many infants go through such phases, and snap out of them, no worse for wear. But Child Two didn’t. He began ignoring his parents. And such speech as he’d gained slipped away.

  There’d been a time when Ms. Two could hold up a ball, and the little boy—her second son—would name it: “ball.” She could point to a book, and he’d say “book.” But then “ball” became “all,” and “book” became “ook,” until his vocabulary dissolved into nothing. “The very last word that he lost was ‘juice,’ ” she tells me when we meet at her home, eight years after the phone call to Wakefield. “It went from ‘juice’ to ‘uice’ to ‘ooo.’ And then it went.”

  No cause or explanation was ever agreed on. Over a period of years, he experienced several regressions, losing speech, play skills, and regard for others, leaving specialists using labels such as “autistic” and “retarded.” But, while regression is sometimes a feature of autism, doctors balked at a precise diagnosis.

  Few parents dawdle in the face of such nightmares. And, marshaling professionals like a Japanese tour guide, this mother wasn’t shy to seek help. Before she called Wakefield, there was a Professor Dryburgh, Dr. Hunter, Professor Neville, and Dr. Tuck. There was a Professor Warner, Dr. Rolles, Dr. Cass, and Ms. Moore. There was a Dr. Richer, Dr. Silveira, Professor Davies, Mr. Martin, Professor Goodyer, Dr. Bhatt, Dr. Cavanagh, and Dr. Wozencroft.