LONDON, UK: It is one of the most serious allegations that could be made about a doctor: manipulating patients' histories to make money. So it is no wonder that the charges, levied by editors of the British Medical Journal (BMJ) in January against the British gastroenterologist, Andrew Wakefield, are still getting close scrutiny. Now an American whistleblower advocacy group has joined the fray over Wakefield, who in 1998 hypothesised a link, now scientifically disproven, between the measles, mumps and rubella vaccine (MMR) and autism.

On November 9, David Lewis of the National Whistleblower's Center in Washington DC published a letter in the BMJ arguing that Wakefield did not commit research fraud. Lewis told another journal, Nature, that he thought the combination of public charges and a slow, secretive investigation had left the public not knowing whom to believe and was unfair to the accused researcher. "[The system] throws people like Andy into a no-man's-land," Lewis says.

Wakefield was the lead author of a 1998 paper in The Lancet (A. J. Wakefield et al. Lancet 351, 637–641; 1998) reporting on the case histories of 12 children who had received the MMR vaccine and developed symptoms of autism or inflammatory bowel disease.

The paper inflamed public fears about vaccines, but it was retracted in 2010 after the UK General Medical Council (GMC) concluded that Wakefield had a charge of serious professional misconduct to answer, in part because it found that his team did not have proper ethical approval for tests performed on the children. Later in the year, the GMC found him guilty of the misconduct charge and revoked his licence to practice as a doctor. By then, more than 12 large-scale epidemiological studies had failed to find evidence of the hypothesised link (J. S. Gerber and P. A. Offit Clin. Infect. Dis. 48, 456–461; 2009) and the MMR vaccine is today regarded as safe.

But was the paper merely mistaken, or a deliberate fraud? Articles by a medical journalist, Brian Deer, published in the BMJ in 2010 and 2011 accused Wakefield of reporting histories for the children that were not consistent with their records and their parents' recollections, at a time when Wakefield was also being paid by lawyers intending to sue MMR manufacturers. Deer's articles themselves did not allege fraud, but on their basis, a BMJ editorial in January 2011 called the paper fraudulent.

Wakefield has always denied allegations of manipulating data or having a financial motive in the Lancet paper, but no institution has yet ruled on the matter. In March, University College London (UCL), which took over divisions of the Royal Free Hospital where Wakefield worked, said it had launched an investigation.

In the meantime, Lewis, a microbiologist and former whistleblower who says he was falsely accused of misconduct after alleging links between human illness and the spreading of sewage sludge, asked Wakefield for the chance to review his files. His claims are not likely to challenge the conclusion based on much other evidence that the vaccine does not trigger autism. But they could complicate the debates about Wakefield's integrity and the UCL investigation.

The documents that Lewis reviewed include confidential forms describing biopsies from the guts of children. The forms were filled out by pathologists Andrew Anthony and Paul Dhillon, who worked with Wakefield at the Royal Free. These documents, Lewis says, are relevant to Deer's charge that records he obtained do not support Wakefield's claims in the Lancet paper that the children had non-specific colitis, a supposed element of an MMR-induced syndrome. On sheets for three of the children graded by Anthony, the handwritten word "colitis" appears, and Dhillon checked a box labelled "non-specific" on 10 forms. Anthony's sheets are dated after the Lancet publication, whereas Dhillon's are dated before.

Lewis believes that the sheets show that Anthony and Dhillon were making good-faith diagnoses of colitis. Anthony, who has left UCL, could not be reached by Nature, and Dhillon indicated that UCL had told him not to comment. (Neither has been accused of manipulating data.)

Before publishing Lewis's letter, the BMJ asked Ingvar Bjarnason, a gastroenterologist at King's College Hospital, London, to review the materials. Bjarnason says he does not believe they are sufficient to support claims in the Lancet paper of a new disease process. He also questions whether "non-specific" on the grading sheets refers to colitis, saying it could refer to any kind of gut changes. But he says that the forms do not clearly support charges that Wakefield deliberately misinterpreted the records. "The data are subjective. It's different to say it's deliberate falsification," he says.

Deer notes that he never accused Wakefield of fraud over his interpretation of pathology records. But he says that records read to him from the Royal Free pathology service clearly stated that the children's gut biopsies were within normal limits, even though they were reported in the Lancet paper as having enterocolitis.

Fiona Godlee, the editor of the BMJ, says that the journal's conclusion of fraud was not based on the pathology but on a number of discrepancies between the children's records and the claims in the Lancet paper. She says she will be calling for a public inquiry into the matter, noting that it has been more than a year since she first informed UCL about concerns over Wakefield's work.

Wakefield denies charges of data manipulation. He says that UCL has yet to officially request his response to any charges and he isn't convinced that the inquiry will give him a fair hearing. A UCL spokesman says that the investigation will be "thorough, fair and wide-ranging". But eight months after announcing its inquiry, the university is still looking for a suitable external chairman.

After extraordinary new confessions, declaring Andrew Wakefield's work as "elaborate fraud", the British Medical Journal (BMJ) is requesting that MPs initiate a parliamentary investigation into the research that claimed autism and bowel disease is caused by the MMR vaccine.

BMJ editor-in-chief Dr Fiona Godlee explains in an article in the journal, that at least six additional research reports by Wakefield need independent investigation, as well as at least six former senior individuals at the London medical school where the work was conducted might have a case to answer regarding their involvement.

Dr Godlee sent a letter to Andrew Miller MP, chair of the House of Commons committee on science and technology, explaining that Parliament must intervene if University College London, where Wakefield worked, does not arrange an independent investigation into the Wakefield case immediately.

Godlee said: "Institutional misconduct is too important to be left to the institutions themselves."

Wakefield, who was formerly an investigator at the Royal Free medical school in Hampstead, north London, was taken off the medical register in May 2010 due to a range of charges, including dishonesty in studies published in the Lancet in 1998. In January 2011, the British Medical Journal concluded that

Wakefield's claims that the MMR vaccine was associated with autism and bowel disease were "an elaborate fraud."

Now, the BMJ has published additional revelations regarding the investigation, eliminating any leftover credibility to Wakefield and his co-authors' claim that they found a novel inflammatory bowel disease connected with the MMR vaccination. No evidence of such disease was provided in the research and nearly all normal discoveries were embellished in the Lancet paper, according to experts after examining unpublished raw data submitted to the British Medical Journal with the view to excuse Wakefield.

Wakefield's report (published in February 1998) indicated that out of 12 children with brain problems taken to the Royal Free hospital, 8 developed autism within a few days of receiving the MMR vaccination, and that 11 of the 12 children had colitis. Following the publication of the paper for 10 years public anxiety increased, levels for vaccination plummeted, and measles re-emerged as an endemic disease across Britain and other places.

According to Godlee, this new data does not reflect well on his 12 authors or clear Wakefield for fraud. "It is impossible to reconcile [the new data] with what was published in the Lancet. The paper talks of enterocolitis and a new bowel disease involving a putative "unique disease process." How could two consultant histopathologists have reported healthy biopsies and then put their names to such a text?" said Godlee.

The British Medical Journal has been at the centre of investigation into the MMR scare. Earlier in 2011 Godlee wrote a letter to University College London reporting six additional reports involving Wakefield which have raised concerns. According to Godlee: "Continuing failure to get to the bottom of the vaccine scandal raises serious questions about the prevailing culture of our academic institutions and attitudes to the integrity of their output. Given the extent of involvement of senior personnel at the highest level, only an independent inquiry will be credible. This is not a call to debate whether MMR causes autism. Science has asked that question and answered it. We need to know what happened in this inglorious chapter in medicine. Who did what, and why?"

In an associated feature editorial published on November 9 on bmj.com, Brian Deer explains what the most recent disclosures add to our knowledge of the Wakefield Case. According to Deer, UCL included Wakefield's claims - not once but twice - in its submission to the UK's investigation evaluation exercise as part of a way to get money.

Godlee explains: "If UCL does not immediately initiate an externally-led review of its role in the vaccine scare, we believe that Parliament should do it. After the effort and time it has taken to crack the secrets of the MMR scare, and the enormous harm it has caused to public health, it would compound the scandal not to heed the warnings from this catastrophic example of wrongdoing."

(Sources: Scientific American, Nature, Medical News Today, November 9, 2011)