Left Brain Right Brain

Regular readers will know that an eminent UK scientist writes the occasional guest blog piece for LB/RB. Here is his piece in the wake of the the Lipkin/Hornig study and the amusing claim that it vindicates Wakefield. Enjoy – Kev.

A scientist who has followed the Wakefield saga from the start sets the record straight.

According to recent newspaper reports Andrew Wakefield is planning to publish his account of the MMR/autism controversy next year, under the title The Lesser Truth. He is currently facing charges of gross professional misconduct at the General Medical Council (the case is expected to conclude in April 2009). Meanwhile, Wakefield and his supporters continue to claim that his research is valid and continue to smear the investigative journalist Brian Deer who exposed the conflicts of interest and dubious ethics – as well as the junk science – behind the claims of a link between MMR and autism. But it was Wakefield who was obliged to back down in court from his libel allegations against Deer. Wakefield was unable to contradict Deer’s claim that he has been “unremittingly evasive and dishonest in an effort to cover up his wrong-doing”.

Here are some truths about Wakefield and his research that may not find their way into The Lesser Truth:

Wakefield was never a respected researcher. His first foray into the Lancet was a controversial paper in 1989 saying that Crohn’s disease was due to problems in the blood supply to the gut (vasculitis). But this was wrong. In the early 1990s he was funded by pharmaceutical companies for research along the same lines, mostly in animal models, and produced a series of low-impact, forgettable, papers.

Wakefield first courted notoriety in 1993 when he claimed to have identified measles virus in Crohn’s disease gut tissue. Coincidently, measles virus can cause vasculitis so it is easy to understand how, from 1989 onwards, Wakefield had to find measles in Crohn’s. We now know this result was not possible: there is no measles virus in Crohn’s disease and the antibodies Wakefield used were not specific for measles either. In Wakefield’s own lab, a good molecular biologist, Nicholas Chadwick, could not find measles in Crohn’s by sensitive molecular techniques. However, Wakefield said he could find measles, using crude techniques using flawed reagents. Suppressing data which ruins your hypothesis is scientific fraud.

In February 1996 Wakefield cooked up the idea that MMR was involved in autism with the solicitor Richard Barr and parent activist Rosemary Kessick. He wrote a research protocol to get into the children’s colons to look for measles virus and gut damage, and applied to the Legal Aid Board for £55K.

By October 1996, the Royal Free team had scoped enough children to provide Wakefield with tissue samples so that his technician could look for measles virus in the guts of autistic children by immunohistochemistry. This was clearly research, without clinical or ethical justification.

By spring/summer 1997 Wakefield had enough cases and enough creative data for his story. He believed that autistic children had gut inflammation and most importantly, he believed that he had discovered the cause – measles virus persisting in the gut from MMR. Wakefield first tried to get this study published in Nature but it was rejected.

Towards the end of 1997 he sent an abstract of this work to be presented at Digestive Diseases Week in the USA in May 1998. He also submitted two papers to the Lancet. The first was accepted and published as the now notorious February 1998 Lancet paper. The second, the study claiming to have identified measles virus in the gut by immunohistochemistry, was rejected. To see Wakefield’s pictures of measles virus in the guts of autistic children go here (slides 37 and 38). The second paper was never published and has now mysteriously disappeared, although Wakefield showed it all over North America for years.

In 2000, Wakefield published a larger series on “autistic enterocolitis”, the new disease he claimed to have identified (Wakefield et al 2000 Enterocolitis in children with developmental disorders. American Journal of Gastroenterology 95: 2285-95). Analysis of the data in this paper has revealed that it was a scam: autistic children do not have a chronic inflammatory bowel disease. Normal findings in children were called pathology, pathological results were re-examined and sexed up, and new abnormalities were manufactured, all to make it appear that these children had gut inflammation (MacDonald TT, Domizio P. Autistic enterocolitis; is it a histopathological entity? Histopathology. 2007 Feb;50(3):371-9).

As the litigation in the UK began to heat up around 2000, the defendants (the MMR manufacturers) started to ask simple questions, such as, where is the paper which shows measles in the gut of autistic children? This was part of the MMR/autism story that was rejected by Nature and the Lancet. Who knows why Wakefield never published it? Maybe he realised it was junk since at the same time his identification of measles virus in Crohn’s disease had unravelled. Maybe he knew that the experts for the defence had looked at the data and the methodology and shown it was junk.

Wakefield now hooked up with Dublin pathologist John O’Leary. O’Leary was supposedly an expert in an unsound and discarded methodology called in cell PCR, which he claimed allowed him to amplify measles genetic material in tissue samples, in this case, from the guts of children with autism, and identify its cellular location. He also set up PCR techniques to amplify measles from samples of gut. The O’Leary lab’s studies of Wakefield’s gut biopsy specimens were published in another notorious paper (Uhlmann et al. Potential viral pathogenic mechanism for new variant inflammatory bowel disease. J Clinical Path: Mol Pathol 2002;55: 84-90).

In his testimony to the Omnibus Autism proceedings in Washington in summer 2007, London-based molecular biologist Professor Stephen Bustin showed the utter incompetence of O’Leary and his lab. He revealed the fact that a result was called positive if the sample contained measles virus but no DNA (a biological impossibility). He also revealed that if they analysed the same autistic sample 6 times and got a positive once, the patient was deemed to be positive, even though they were also getting positive measles results out of samples of pure water.

It seems that O’Leary has belatedly seen the error of his ways: in the recently published Hornig study, his lab – in common with other labs in the USA – failed to find measles in samples from autistic children (Hornig et al 2008 Lack of association between measles virus vaccine and autism with enteropathy: a case-control study. PLOS One 3(9):e3140). The attempts by Wakefield and his acolytes to claim that the Hornig study vindicates the Uhlmann paper are preposterous. Distancing himself from Wakefield as fast as is possible for any man of 20 stone, O’Leary cleaned up his lab and did things properly.

A review of the career of Andrew Wakefield is a trawl through the underbelly of science. Wakefield did not do experiments to seek the truth – he did experiments to confirm his own beliefs. He produced junk science for over a decade and did immense damage to patients with Crohn’s disease, and autistic children and their parents. Hopefully the GMC will nail the charlatan, and show some sympathy for the Royal Free clinicians who thought Wakefield was honest. The Andy Wakefield show has now moved to the USA where he can get the attention he craves and he can play the role of the selfless seeker of truth whom the establishment had to silence. Being a victim is a good career move for him. It will help Thoughtful House sell junk therapies for autism to desperate parents and allow Andy to live in a really big house, where he can entertain his showbiz friends. He really wanted to be a famous scientist, but he was rubbish at that, so he had to become (in)famous by other means.