How to create a disease

This piece is once again guest written by ‘Nigel’, a scientist working in the field whos real name is not actually Nigel ;o)

Followers of Andy Wakefield may not have come across a little spat which took place in the correspondence section of the journal “ Histopathology” last year. It is all to do with “ autistic enterocolitis”, the alleged inflammatory bowel disease described by Wakefield and colleagues in 1998 in the infamous Lancet paper. It is worth remembering that although the MMR-autism link garnered all the publicity, a key intermediate in the link was that measles persisted in the gut, resulted in enlarged lymphoid follicles, which then somehow caused this “ autistic enterocolitis”. At Thoughtful House in Austin, Texas, Wakefield and his acolyte Artie Krigsman, are now trying to make a buck out of treating this condition.

Professors Tom MacDonald and Paola Domizio from Barts and the London School of Medicine in London were experts for the defense in the UK MMR litigation against the vaccine manufacturers out of which Wakefield trousered one million dollars. MacDonald is a pre-eminent gut immunologist with an international reputation and was recently awarded the President’s Medal of the British Society for Gastroenterology for his scientific achievements. Domizio is an extremely well known gut pathologist and is also a senior figure in the Royal College of Pathologists in the UK.

The gist of their article (Histopathology. 2007 50:371-9) was that autistic enterocolitis does not exist. In a forensic dissection of the key paper by Wakefield and colleagues in the Am J Gastroenterology in 2000 (Am J Gastroenterol. 2000 95:2285-95), MacDonald and Domizio clearly showed that the so-called enterocolitis was due to Wakefield incorrectly deeming enlarged lymphoid follicles in the gut as pathological abnormalities, and that he had also created new and unsubstantiated pathological abnormalities to give the impression of gut pathology. The image of enterocolitis in an affected child shown in this paper was an extremely highly magnified picture of a small piece of tissue, which may in fact have come from one of the original Lancet 12 (in order to bump up the numbers of patients studied, Wakefield just reported the original Lancet 12 again). This is a familiar Wakefield tactic, his “representative” images are always taken at an extremely high magnification on the microscope, presumably to hide the fact that the rest of the tissue is normal. MacDonald and Domizio also shredded other Wakefield papers of the same ilk in their article.

Key to this piece of detective work by Domizio and MacDonald was a table in the Am J Gastro paper where these invented histological abnormalities were shown. In his response ( Histopathology 2007 50:380-4) Wakefield did not address any of the substantive points raised by MacDonald and Domizio, but stated that the pathological descriptions in the table were nothing to do with him, but were the work of Prof A Dhillon at the Royal Free Hospital in London, who was not an author of the paper. Unfortunately for Wakefield, Dhillon also wrote to the journal to say that it was nothing to do with him either (Histopathology 2007 50:794). Dhillon showed his version of the table, which unsurprisingly, because Dhillon is a bona fide pathologist, contained none of the new invented abnormalities. So we have an impasse, though not enough of an impasse to stop Wakefield publishing another paper in 2005 (Eur J Gastroenterol Hepatol 17:827-36) showing the same table again, and remarkably, reporting the Lancet 12 for at least the third time! Wakefield produced no response to MacDonald and Domizio’s suggestion that since the histopathology slides from the autistic children seen at the Royal Free Hospital in London are available, it would be a straightforward exercise to have these analysed in an anonymous and independent fashion to put this question to rest.

In response to Wakefield’s defence of his work, the editor allowed MacDonald and Domizio a final say, where they demolished Wakefield again (Histopathology 2007, 51, 552–3).

Although all of this might seem highly technical, histopathological diagnosis of gut disease is a highly skilled art, with extremely high standards, and it is scientific vandalism for non-pathologists such as Wakefield to create new and non-existant abnormalities and then use them to burden children and parents with a life-long inflammatory bowel disease. The best example of this sleight of hand is his definition that a tissue section from the gut of an autistic child was abnormal if it contained a lymphoid follicle. However when the gut biopsies were taken at colonoscopy from autistic children, lymphoid follicles were specifically targeted for sampling because they wanted to look for measles in these tissues. So it is obvious that all will have pathology if one uses this invented criteria.

Throughout this saga, Wakefield has traded on the fact that autistic children do have real gut problems. However instead of attributing these problems in the majority of children to a combination of chronic and severe constipation, fecal impaction, unusual diet, diarrhea, bloating, parasites, gas etc, he had to find a new disease! However the pediatric gastroenterologists in charge of these children at the Royal Free knew what the problem was, when they wrote in the Lancet in 1998, that following cleansing of the colon needed for colonoscopy, many children underwent rapid symptomatic improvement which was maintained if constipation was avoided ( Lancet 1998;351:908). So there you have it, an inflammatory bowel disease treatable by cleansing the colon!

An interesting post-script to all this is that when challenged with the fact that the alleged “enterocolitis” in autistic children is not different from the mild changes and ileal lymphoid hyperplasia seen in chronically constipated, developmentally normal children, Wakefield and Krigsman are now saying that the constipation in autistic children is different! Give us a break !

PS. MacDonald was also an expert witness last year in the Hazelhurst versus HHS case in the USA. In his testimony MacDonald re-iterated in some depth the extent of Wakefield’s rogue and junk science, going back all the way to his identification of measles virus in Crohn’s disease using reagents which were not specific for measles virus. However he picked up yet another deception in the Am J Gastro paper. Much of the paper deals with the alleged lymphoid hyperplasia in the ileum of autistic children, graded by Wakefield on a score 0-3, with 0 being no follicles and 3 allegedly an undefined “severe” lymphoid hyperplasia. To illustrate the colonoscopic appearances of grades 0-3, a panel of photographs purportedly showing the different grades is included as Figure 1 of the paper. The date and time each photograph was taken is reproduced in figure. The image of alleged grade 0 ileal lymphoid hyperplasia (ILH) was taken on the same day and only 1 minute 54 seconds before the image of alleged grade 3 ILH. It is impossible to remove a colonoscope from 1 child and scope another child, reaching the ileum in 1 minute 54 seconds. Therefore the grade 0 and grade 3 images were taken from the same child; the grade 0 image most probably from the caecum ( the part of the colon just after the ileum) and the grade 3 image from the terminal ileum.