An article in this week’s BMJ questions the reality of a new bowel condition in autistic children which is called “autistic enterocolitis”. The description of this condition was introduced in a now infamous paper by Dr Andrew Wakefield and colleagues published in 1998 by The Lancet. It was recently retracted.

Journalist Brian Deer tries to understand how the biopsy reports that formed the basis of the study were developed. In addition, an associated editorial questions the existence of autistic enterocolitis.

In 1996, a solicitor secured the services of Dr Andrew Wakefield to assist in the launching of a speculative lawsuit against drug companies that manufactured MMR vaccine. He found, what he called at the time, “a new syndrome” of bowel and brain disease caused by vaccines.

Brian Deer reveals some inconsistencies. The biopsy reports from the Royal Free Hospital’s pathology service on 11 children included in The Lancet study showed that eight out of 11 were interpreted as being largely normal. But in the paper, 11 of the 12 children were said to have “non-specific colitis”. It was described as a clinically significant inflammation of the large bowel.

It appears that the biopsies were first reported on by Dr Susan Davies. She is a consultant histopathologist and co-author on the study. But before final publication, they were also seen and interpreted by three other co-authors.

During cross examination before the General Medical Council, Dr Davies said that she had initially been concerned about the use of the term “colitis” in the Lancet paper because she herself had found nothing abnormal in the biopsy sections. However, she said she was reassured by the “formalized review” of the biopsies by her three colleagues.

Deer explains that this apparent concurrence of four pathologists gave strength to the finding of a new bowel disease. However, there is no suggestion in the paper that the second assessment caused findings to be substituted or altered.

Deer asks: How many peer reviewers would have felt comfortable approving the paper if they had known that the hospital pathology service reported biopsy specimens as largely normal, but they were then subjected to an unplanned second look and reinterpreted?

Professor David Candy is a pediatric gastroenterologist at St Richard’s Hospital, Chichester. He reviewed the paper in 1997. He answered “no” indeed, he would not have felt comfortable. “That’s an example of really naughty doing – to exclude the original pathology findings.”

Therefore, Deer asks what conclusions can be drawn from all this? The biopsy slides are no longer available, and cannot be re-assessed. All that exists are Dr Davies’ pathology reports. Independent specialists seem to concur that she considered what they showed as largely unremarkable.

Professor Tom MacDonald, dean of research at Barts and the London School of Medicine and co-author of Immunology and Diseases of the Gut remarks: “If I was the referee and the routine pathologists reported that 8/11 were within normal limits, or had trivial changes, but this was then revised by other people to 11/12 having non-specific colitis, then I would just tell the editor to reject the paper.”

In an associated editorial, Sir Nicholas Wright, also from Barts and the London, comments that all histopathological interpretation is a matter of opinion. But, he says, we should always ask how reliable that opinion is.

Regarding autistic enterocolitis and whether it exists, several studies have shown a link between inflammatory pathology and autistic spectrum disorder. However, in view of the limited data, he believes that any firm conclusion would be unwise.

Wright says in conclusion: “We should remember, as recent experience in several fields has shown, that although science has its defects, it is a self correcting process. Time is, perhaps, the wisest counsellor of all.” He continues: “In the meantime, this case offers a salutary reminder for researchers and journal editors alike that coauthorship means bearing responsibility for what is written.”

“Wakefield’s “autistic enterocolitis” under the microscope”
Brian Deer
Autism Research
BMJ – 17 April 2010 – Volume 340

“Does autistic enterocolitis exist?”
Nicholas Wright
BMJ 2010; 340:c1807
doi: 10.1136/bmj.c1807
bmj.com

Written by Stephanie Brunner (B.A.)