12.2.04
Dear Mr Deer,
I am sorry that I am writing
this letter from the US and outside office
hours. I hope that having read the letter,
you will understand why I have written, not
least so that you may be able to read this
several times and give due consideration to
what I have said.
At the same time I am frustrated
that having requested, via Abel Hadden,
written questions or allegations more than
eight weeks ago, I am left to respond at a
few hours notice, from Flintrock Texas,
without access to the necessary paper records
that are of relevance to your allegations.
Your allegations appear to focus
upon two issues:
(i) the accusation of
inappropriate investigation of children
with autism; and,
(ii) apparent
misappropriation/misuse of funds from the
Legal Aid Board
I will deal with these in turn.
On the first issue you are
completely mistaken. Children with
developmental disorders and undiagnosed
gastrointestinal symptoms were referred to
Professor John-Walker Smith or his junior
Consultant colleagues, and not to me. Since I
was a Reader in the Department of Medicine
(not Paediatric Gastroenterology) and my work
was exclusively research based, with no
clinical commitment, at no time was I
responsible for the clinical care of these
children, or for making the decision to
perform ileo-colonoscopy or upper
gastrointestinal endoscopy on these, or any
other children.
All decisions to undertake these
procedures were based solely on clinical
indications due to the children's symptoms
and were not in any way influenced by whether
the child was part of the MMR class action
litigation. Professor Walker-Smith and his
colleagues were, at this time, strongly
opposed to the litigation and any involvement
in it. To suggest that "these procedures
were not clinically indicated" is
factually incorrect and impugns the
reputation of some of the country's most
respected paediatric gastroenterologists. My
contract with the Legal Aid Board (LAB) was
in no way, nor could it have ever been, the
indication for the clinical procedures
carried out on these children. Neither I nor
my medical colleagues would ever countenance
the clinical investigation of a patient in
the absence of a clinical indication. The
indications in this case were specificallv
and exclusively the symptoms from which these
children suffered - regressive encephalopathy
and gastrointestinal symptoms, following
viral exposure - and the decision to conduct
these clinical investigations rested not with
me, but with the paediatric
gastroenterologists responsible for their
care. As an indication of this, both MRIs and
cerebrospinal fluid analysis were stopped
during the course of the study of the first
12 children since they were not informative
and therefore, deemed no longer clinically
indicated.
You seem to be unaware of the
fact that our collaborative effort at the
Royal Free has made an important discovery -
a novel inflammatory bowel disease in
children with autism, a group of children
that had been effectively discarded by the
medical profession as hopeless and
untreatable. The evidence for this discovery
has been peer-reviewed and published in
eminent medical journals and has been
confirmed by physicians and pathologists at
several centres in the US including Harvard
Medical School, the University of Maryland
Medical School and Lennox Hill and Mount
Sinai Hospitals, New York. For your
information, I have included details of these
studies below'. To suggest, as you do,
without qualification, that the appropriate,
necessary and compassionate investigation of
these children was "not
clinically-indicated" is an
extraordinary statement coming from a
newspaper journalist and it has absolutely no
basis in fact. It also explicitly accuses all
the clinicians involved in the care and
treatment of these unfortunate children of
grossly unethical medical practice. I insist
that you withdraw this accusation in its
entirety.
As far as Ethical Practices
Committee approval is concerned, this was
sought as soon as it became apparent that the
children with autism who were undergoing
appropriate medical investigation for their
clinical symptoms actually had an
inflammatory intestinal disease. There is
absolutely no requirement for Ethical
Practices approval for the investigation of a
patient on clinical grounds. At the point at
which the clinical findings justified a more
detailed study of the underlying pathology
with a view to publication, the relevant
approval was sought and obtained. Pending the
approval of the proposed study it remained
entirely reasonable to follow normal practice
and continue with the clinical investigation
of potentially affected children. It was,
however, necessary to obtain Ethical
Committee approval for the purposes of
reporting our findings. This approval was
duly obtained. As stated in the Lancet paper,
therefore, the study of these children was
approved by the Ethical Practices Committee
of the Trust. This issue has been discussed
by Professor Walker-Smith with the Editor of
the Lancet and resolved to their complete
satisfaction.
Once again, although I was
involved in the preparation of the Ethical
submission, the senior clinician with overall
responsibility for this process was Professor
Walker-Smith and it was to him that
correspondence and documentation was
referred. The process of designing the
studies, writing and amending the Ethical
Practices submission and writing the papers
that derived from the studies was the shared
responsibility of all of those involved, and
was conducted with full cooperation of the
relevant parties. To single me out in this
process demonstrates a clear misunderstanding
of the processes involved.
Let me now turn to the issue of
my involvement with Richard Barr and the
Legal Aid Board (now the Legal Services
Commission).
In 1996 I was approached by
Richard Barr and Kirsten Limb of Dawbarns
solicitors, who had become aware of my
group's interest in children with
inflammatory bowel disease, measles virus
and, for some children, developmental
regression leading to autism. It is important
to state that the first clinical referrals of
children with regressive autism and
gastrointestinal symptoms to Professor
Walker-Smith had started in 1995, some time
before I ever became aware of the existence
of Richard Barr and the MMR litigation.
Prior to meeting with Richard
Barr, I had had no experience of medical
litigation whatsoever. We discussed, at great
length, the commonalities between the
children whose parents had approached them
describing regression after MMR vaccination
with concomitant bowel symptoms and the
children that we were seeing in the clinic at
the Royal Free. Some of the children that
were referred to the Royal Free for clinical
investigation were also involved in the
emerging litigation against the vaccine
manufacturers; it was this group that was to
form the basis of the LAB contract. It is
important to state that by the time of my
meeting with Richard Barr several children
with this disorder had already been
investigated and diagnosed at the Royal Free.
During the course of my discussions with
Richard Barr, I was asked what it would take
to establish whether MMR vaccine had either
caused or materially contributed to the
syndrome of bowel disease and autistic
regression from which these children
suffered. The intestinal disease was
consistent with a chronic viral pathology, a
finding that has been endorsed by all of the
observations made in follow-up studies cited
above. The areas of swollen lymphoid tissue
were potentially a nidus (nest) for the
persistence of any causal virus. Measles
virus can cause similar swelling of the lymph
glands in the intestine and therefore this
was an appropriate place to start looking for
measles and other possible viral agents. I
proposed that an initial scientific approach
would be to use the technique of
immunohistochemistry, which seeks to detect
and localize specific viral proteins in the
biopsy tissue. I proposed that intestinal
biopsies from children with autism should be
compared with similar biopsies from
developmentally normal children also
undergoing investigation of gastrointestinal
symptoms. Richard Barr asked me what it would
take to perform such studies. The simple
answer was funding, in order to pay the
salary of a suitably qualified laboratory
scientist and cover the cost of the reagents.
I was asked to budget the likely
associated costs of the viral studies, and in
addition, the costs of any further expenses
that might possibly be incurred in the
investigation of these children and putting
the relevant findings into a legal context.
Since I had no experience of litigation or
the Legal Aid Board (LAB), I was assisted in
defining possible expenditure by Richard
Barr.
Agreement was reached with John
Baker of the LAB, Richard Barr and myself; a
laboratory scientist was duly employed and
the viral detection work was started. Ethical
Committee approval for the studies was
obtained and the protocol was agreed upon by
the researchers involved. This work provided
positive evidence of measles virus protein in
the tissues of the autistic children at a
significantly higher frequency than in
control, developmentally normal children.
Although the studies more than consumed the
funding provided by the LAB, the results were
sufficiently compelling that the work was
expanded to involve larger numbers of
children and the use of complementary viral
detection techniques. The funding received by
the LAB was used exclusively to fund this
aspect of the study - virus detection -
which, in the event was considerably
underbudgeted. The confirmatory aspects of
this study were subsequently funded by
research grants. The results of these studies
were duly presented to the LAB. In addition
the results of these studies have been
presented to scientific meetings following
peer-review, and have been submitted for full
peer-review publication and have been
provisionally accepted for publication in
2004. Due acknowledgement of the funding
received from the LAB for the preliminary
aspects of this work and all other sources
for its completion, will accompany the paper.
So far as I recall, The LAB did
not fund any of the investigations reported
in the Lancet 1998 publication and
consequently the LAB received no
acknowledgement in this paper.
It should be stated explicitly,
that none of the viral investigations
described above, were in any way routine
services provided by the NHS, nor were they
available from any routine diagnostic
laboratory. These studies did not constitute
part of the standard of care for children
undergoing gastrointestinal investigation,
nor were any of these investigations funded
from NHS resources. The studies constituted
strictly scientific research that was
designed to test the hypothesis that measles
virus protein was present in the autistic
children and not in developmentally normal
controls.
Absolutely no funding provided
by the LAB was used for routine clinical
investigations, including ileo-colonoscopy.
Although this procedure was included in the
comprehensive list of possible projected
costings outlined to the LAB, it was clear
that since the procedures were clinically
indicated they were covered as part of the
children's routine investigation as NHS
patients. At the conclusion of our
investigations no claim for reimbursement of
these aspects of the work were made, and none
received. All matters related to the
investigations were the subject of ongoing
discussions between Richard Barr and me, as
the investigations progressed. The conclusion
of this aspect of work from the LAB's
perspective, was a detailed report submitted
by me in 1999 that described the findings and
conclusions. The LAB was fully aware of the
report's findings and appear to have been
entirely satisfied with the outcome. At no
time have any questions on the above matter
been referred to me or received by Richard
Barr. If the LAB has any questions in
relation to these matters, I will be happy to
deal with them directly.
In summary therefore your letter
of 10th February 2004 while directed to me,
contains allegations of the gravest nature.
You have cast aspersions on the reputations
of all the many doctors and scientists
involved in this work at that time. You have
called into question the moral and ethical
commitment of doctors and researchers in a
most critical field: appropriate and ethical
investigation of autistic children who more
than any others have no voice to be heard.
You make the point yourself that childhood
immunisation is a vital matter of public
concern and that research into this area
requires those involved to be careful,
thorough, open and honest. I fully accept and
adhere to this vital principle and continue
to strive, though diligent research and
publishing of papers in peer reviewed
journals to elucidate the relationship
between the MMR vaccination and the new
variant inflammatory bowel disease identified
in these children with regressive autism.
Adherence to strict medical and ethical
principles has cost me and my colleagues
dear. I believe that a similar duty weighs on
those investigating and reporting on this
controversial area in the media.
You seem to imply, in closing,
that the "facts" that you seek to
reveal will in some way make redundant, all
the science that has been conducted by me, my
colleagues, and other researchers around the
world and in some way influence the risk of a
measles epidemic. Your demonstrably false
accusations in no way diminish the scientific
validity of our findings. Furthermore, it is
science and science alone that is necessary
in order to counter the existing basic and
clinical evidence in favour of some form of
an association between the MMR vaccine and
autism in some children.
Yours sincerely,
Andrew J Wakefield MB.BS, FRCS,
FRCPath
c.c. Richard Barr, Abel Hadden,
Kirsten Limb, John Walker-Smith, Robert
Sawyer,
Wakefield AJ, Murch SH,
Anthony A,, Linnell J, Casson DM, Malik M, et
al. Ileal-lymphoid nodular hyperplasia
nonspecific colitis, and pervasive
developmental disorder in children. Lancet.
1998:351:637-641
Uhlmann V., Martin CM., Shiels
0., Pilkington L., Silva I., Lillalea A.
Murch SH., Wakefield AJ., O'Leary JJ.
Potential viral pathogenic mechanism for new
variant inflammatory bowel disease. Mol
Pathol. 2002;55:84-90
Wakefield AJ., Anthony A., Murch
SH., Thomson M., Montgomery SM., Davis S.,.et
al. Enterocolitis in children with
developmental disorders. Am J
Gastroenterol. 2000;95:2285-2295
Furlano R,. Anthony A., Day R.,
Brown A., McGavery L., Thomson M., et al.
Quantitative immunohistochemistry shows
colonic epithelial pathology and y&T cell
infiltration in autistic enterocolitis. J
Pediatrics 2001; 138:366-372
Torrente F, Machado N, Ashwood
P, et al. Enteropathy with T cell
infiltration and epithelial IgG deposition in
autism. Mol Psych. 2002;7:375-382
Ashwood P, Murch SH, Anthony A,
Pellicer AA, Torrente F, Thomson M,
Walker-Smith JA, Wakefield AJ. Intestinal
lymphocyte populations in children with
regressive autism: Evidence for extensive
mucosal immunopathology. Journal of
Clinical Immunology, 2003;23:504-517
HORVATH K, PAPADIMITRIOU JC,
RABSZTYN A, DRACHENBERG C, TILDON JT.
Gastrointestinal abnormalities in children
with autistic disorder, J Pediatr. 1999;135:559-63
SINGH VK, LIN SX, YANG VC.
Serological association of measles virus and
human herpesvirus-6 with brain autoantibodies
in autism. Clin Immunol Immunopathol 1998;89:105-8
SINGH VK, JENSEN RL, Elevated
levels of measles antibodies in children with
autism, Pediatric Neurology, 2003;28:292-294
HORVATH K AND PERMAN JA, Autistic disorder
and gastrointestinal disease, Current
Opinion in Pediatrics 2002;14:583r587
Krigsman A. Testimony before US Oversight
Committee on Government Reform. June 2002.
Krigsman A. Report to the Legal
Services Commission, June 2003
Harpaz N. Report to the Legal
Services Commission, June 2003
Ashwood P, Murch SH, Anthony A,
Hayes C, Machado MP, Torrente F, Thomson MA,
Heuschkel R, Wakefield AJ., Mucosal and
peripheral blood lymphocyte cytokine profiles
in children with regressive autism and
gastrointestinal symptoms: Mucosal immune
activation and reduced counter regulatory
interleukin-10. Gastroenterol. 2002;122
(Suppl):A617
Wakefield AJ. Enterocolitis,
autism and measles virus. Mo/ Psy. 2002;7
(Suppl 2):44-6.
Wakefield AJ, Puleston JM,
Montgomery SM, Anthony A, O'Leary JJ, Murch
SH., Review article: the concept of
entero-colonic encephalopathy, autism and
opioid receptor ligands, Aliment Pharmacol
Therapeut 2002;16:663-674
O.Sheils, P.Smyth. C Martin.
J.J. O'Leary. Development of an 'allelic
discrimination' type assay to differentiate
between the strain origins of measles virus
detected in intestinal tissue of children
with ileocolonic lymphonodular hyperplasia
and concomitant developmental disorder. J
Pathol. 2002; 1 98(suppl), 5A
Wakefield AJ. Measles, mumps,
and rubella vaccination and autism. NEJM. 2003;348:951-4