- FOCUS:
MMR - THE TRUTH BEHIND THE CRISIS
The
Sunday Times (London) February 22 2004
Six years ago Andrew Wakefield linked MMR
with autism. It sparked a national health scare that
could yet see children die. Brian Deer reveals the
doctor’s secret
To call a national press conference in order to
announce the results of a scientific trial is rare.
For a prestigious teaching hospital to do so for a
study involving just 12 children is unprecedented. So
when journalists were called to attend an urgent
press briefing at the Royal Free hospital in London
in February 1998 they arrived expecting a scoop.
Under
television lights, five doctors, including the dean
of the medical school, lined up to make their
announcement. They had, they informed the hushed
room, important news from the front line of medicine:
injections of the combined measles, mumps and rubella
vaccine (MMR) had been linked for the first time to a
bowel disorder and the onset of a severe form of
regressive behaviour, generally known as autism, in
children.
Richard
Horton, the dapper young editor of The Lancet, waited
expectantly in his office for the reaction. It was
shocking news by any standards. Government policy
dictated that every child should receive the first of
two MMR inoculations between 13 and 15 months.
Thousands of jabs were being given daily. Now parents
were being told that the vaccination might be
associated with a form of serious brain damage in
children.
Advance
copies of The Lancet’s sensational study were
quickly distributed. “Twelve children were
referred to (the hospital) with a history of normal
development, followed by a loss of acquired skills,
including language, together with diarrhoea and
abdominal pain”, read its remarkably
media-friendly opening page. “Onset of
behavioural symptoms was associated, by the parents,
with measles, mumps and rubella vaccination in eight
out of the 12 children.”
Eight
out of 12: it was a stunning proportion. Worse, the
damage had become evident on average just “6.3
days” after the jabs were given. Professor Arie
Zuckerman, dean of the medical school, then sounded a
word of caution. It was “absolutely
essential” that public confidence in MMR was not
damaged by the publication of the study. Eight
children did not, after all, provide proof of a link
between MMR and autism, he noted.
However,
if Zuckerman was cautious, others were not. At the
centre of the speakers’ table sat the principal
author of the study, Dr Andrew Wakefield. Cutting a
dashing and charismatic figure, the young
gastroenterologist had a very different message to
impart. Yes, it was just one study and yes, there was
no proof, but he personally believed that action was
needed.
“One
more case of this is too many,” he declared.
“It’s a moral issue for me and I can’t
support the continued use of these three vaccines
given in combination until this issue has been
resolved.” He wanted single jabs.
Until
then the emerging public debate over MMR had been
based on little more than anecdote. Now it had been
given the imprimatur of The Lancet and an urgent call
for government intervention. The result was
explosive. “Alert over child jabs” shouted
the front page of The Guardian the next day.
“Ban three-in-one jab urge doctors” said
the Daily Mail. Thousands of similar newspaper
stories, television and radio broadcasts followed
over the next few months.
GPs’
surgeries were inundated with calls from parents and
vaccination rates started to fall. Six years on and
an epidemic of measles, which can maim and even kill,
now threatens. Overall, the inoculation rate has
fallen to just 79% — well below the 95% needed
to confer “herd immunity” in crowded
schools, nurseries and playgrounds.
David
Elliman, a consultant community paediatrician at
Great Ormond Street hospital, warned last week that
with almost half of children unvaccinated in some
parts of London, the risk of a death from measles had
become real. He said that outbreaks of the disease
caused by inadequate vaccine coverage in Italy,
Ireland and Holland had led to deaths in recent
years.
“The
worry is that the coverage here is so low in some
areas that this could happen here, and people should
be made aware of that,” he said.
At
the Department of Health and in the wider medical
establishment, experts were deeply concerned by the
reaction to The Lancet study. Yes, the journal had
pushed it and yes, officialdom had gained little in
the way of public trust after the debate over
“mad cow” disease, but Wakefield appeared
not so much an objective scientist, more as a man
with a mission. He had even written to the department
attacking the MMR vaccination before his own research
was completed.
“I
am writing to you in order to express formally my
anxieties over your intention to re-vaccinate all
pre-school children,” he wrote on September 6,
1996 to Sir Kenneth Calman, then the
government’s chief medical officer. The letter
closed with the blunt instruction: “Do not
re-vaccinate.”
Now a
Sunday Times investigation has revealed that
Wakefield’s Lancet report was not the objective
piece of science that it had appeared to be. All
along he has kept a secret from the public, from The
Lancet and even from his colleagues. His secret was
this: in August 1996 — the month before he
dispatched his letter to Calman and a month before he
applied for ethical approval for the Lancet study
— he had secured up to £55,000 from the Legal
Aid Board specifically to investigate a possible link
between MMR and autism in respect of 10 named
children.
Of
the eight children whose parents were eventually
reported in The Lancet as having associated the jab
with the onset of their child’s autism,
“four, perhaps five” were covered by the
legal aid contract. Not only did Wakefield know at
the time of publication that the parents of these
children had an interest in seeing a scientific link
between MMR and autism established, but he was also
being funded to investigate that possibility. Only if
he were successful in establishing that link would
the children’s parents be able to sue for
compensation. He knew all this but declared none of
it in the Lancet study, to his principal co-authors
or to the public.
All
the public got was Wakefield’s warning against
MMR and the concluding paragraph of his study which
stated: “In most cases, onset of the symptoms
was after measles, mumps and rubella
vaccination.” Through the offices of public
relations advisers and lawyers, Wakefield continues
to maintain that he acted properly. But the
revelations do more than cast his original study in a
new light; they taint his findings.
Even
Horton, a former colleague of Wakefield, said last
week that in retrospect The Lancet should never have
published his study. Late on Friday, after being
shown the evidence in confidence by The Sunday Times,
he chose to make a public statement.
“If
we had known the conflict of interest Dr Wakefield
had in his work, it would have been rejected. As the
father of a three-year-old who has had the MMR, I
regret the adverse impact this paper has had,”
Horton said.
HOW
did Wakefield end up publishing something so
potentially misleading in a highly respected medical
journal? “Andrew always wanted to be a
surgeon,” recalled his mother Dr Bridget
Wakefield, a retired GP in Bath who is married to a
neurologist and is the daughter and granddaughter of
doctors. “He’s very like my father. If he
believed in something, he would have gone to the ends
of the earth to go on believing.”
After
qualifying in medicine and training as a surgeon in
Canada, Wakefield joined the Royal Free as a research
scientist. Among the bowel problems that he had seen
during his training was Crohn’s disease, an
ulcerating inflammation of the gut. The more he
studied it, the more he suspected that it was caused
by a common virus: measles.
In
the early 1990s Wakefield published several studies
proposing a measles-Crohn’s link. Although the
studies did not lead very far, he kept the faith and
persevered. At the same time Richard Barr, a
solicitor in Norfolk, was developing a practice in
litigation against drug companies. Barr had pursued
some cases against Opren, an arthritis drug, and in
the early 1990s he learnt of concerns about MMR,
which had been introduced in Britain in 1988. A
number of clients came to him concerning legal action
against three drug companies which manufacture MMR:
GlaxoSmithKline, Aventis Pasteur and Merck.
Barr
identified clients through newsletters and publicity.
“Vaccine damage is not some capricious
concept,” he claimed in one pamphlet, “but
is very real and is demonstrable using scientific
principles.”
Jackie
Fletcher, one of Barr’s clients, ran a
campaigning group called Jabs which involved
concerned parents. It is not clear exactly when
Wakefield and Barr first came into contact. Barr
thinks he met Wakefield in 1994. A colleague in
Dawbarns, the firm where Barr then worked, says it
was in 1995. Last week Wakefield said it was 1996,
but then conceded that it might have been 1995.
What
is clear is that when the two met, a flurry of
activity ensued. Damaged children in Barr’s
network started to be referred to the Royal Free.
This was an “unusual” pattern, The Lancet
said on Friday.
According
to Barr, he and Wakefield began to talk regularly by
telephone. Between the two of them a hypothesis was
taking shape: that measles from MMR was damaging the
gut, causing inflammation. Harmful chemicals were
then getting into the blood, resulting in brain
damage and autism. It was a neat idea but little more
than that. Then, sometime in the first six months of
1996, Barr and Wakefield approached the Legal Aid
Board to fund the clinical investigation of 10
apparently brain-damaged children. In August 1996 the
board granted them £55,000 to investigate possible
links between MMR and autism, The Sunday Times has
established.
Wakefield’s
clinical colleagues at the Royal Free — who
physically examined the children — say they were
not told of the Legal Aid Board contract by
Wakefield. All the children were presented to them as
ordinary patients referred by their GPs. Soon
afterwards these same doctors — surprised at
what they had seen in the children — applied to
the Royal Free’s ethics committee to undertake a
study for publication on up to 25 children with
behavioural disorders who had had measles vaccine.
Wakefield’s
name was also prominent on the proposal which was
submitted in September 1996. It was this study that
would give rise to the Lancet article. There was no
disclosure on the ethics application form of the
legal aid contract. A few of the children were
already under investigation but now the numbers
increased. Each was subjected to a battery of tests,
some highly invasive: one involved manoeuvring a 4ft
fibre-optic endoscope deep into the bowel; another
was to hunt for measles through a lumbar puncture or
spinal tap.
Wakefield
says these investigations were judged to be
“clinically indicated” by his medical
colleagues and therefore justified. They did not
know, however, about the £55,000 legal aid contract.
Barr was delighted for his clients at the way things
were going. Indeed, when interviewed by The Sunday
Times last month, he said: “We weren’t
trying to get an independent paper published under
the carpet. I remember noting at the time that the
funding acknowledgment wasn’t there, but it
didn’t seem to be a big deal . . . things have
moved on since then.”
The
issue of funding aside, there is another, perhaps
more fundamental, issue. After lengthy investigations
by The Sunday Times, Wakefield finally admitted last
week that “four, perhaps five” of the
children in his Lancet study were among the 10 named
in the legal aid contract. Was it four or five?
“Let’s make it five,” he said. The
questioning went on. Were they litigants? Yes. Was he
being paid to help them to build their case? Yes.
Were his colleagues told that they had ended up in
the Lancet sample? I don’t recall. Did he reveal
the conflict of interest to The Lancet as its rules
explicitly require? No. Why not? “I believe that
this paper was conducted in good faith. It reported
the findings. There was no conflict of interest. Do
we have any reasons (now) to change our opinion? No,
but again it’s a debate.”
The
Lancet yesterday described Wakefield’s
continuing insistence that he had done nothing wrong
as “perverse”. John Reid, the health
secretary, has called for a General Medical Council
inquiry. Others are equally bemused. Elliman said he
was amazed that Wakefield had used children who were
litigating as his subjects.
“These
are people with a clear vested interest in the result
of the research and it would have been appropriate to
let that be known,” he said. “Wakefield has
got himself into a very difficult position.”
Wakefield
says that in 1997, as The Lancet study was being
prepared for publication, he and his colleagues had
another “debate”. It was about whether to
include the key finding that the parents of eight out
of 12 children associated the jab with the onset of
brain damage in their offspring.
His
co-authors, however, say they did not have the full
facts: Wakefield had not told them of the
“overlap” of five children or even of the
existence of the legal aid contract. When Professor
John Walker-Smith, the lead clinician named on the
Lancet study, was told of Wakefield’s funding,
he said that he was “astounded”.
“We
were seeing these patients by clinical need and we
were reporting the first patients we saw,” he
said. “There was no awareness of any legal
involvement when we saw these children.”
THERE
were several key points at which Wakefield could or
should have declared his and the children’s
involvement in the litigation. The Lancet’s
rules for its authors are clear: “The conflict
of interest test is a simple one. Is there anything .
. . that would embarrass you if it were to emerge
after publication and you had not declared it? The
editor needs to be informed and will discuss with you
whether or not disclosure in the journal is
necessary.”
Did
Wakefield hold discussions? No. Is he now
embarrassed? “I have no regrets,” he said.
Shouldn’t he have disclosed that he was acting
for Barr’s clients? “I don’t agree . .
. clearly there is a debate . . . we can argue about
this.” On Friday, after considering The Sunday
Times’s evidence, questioning Wakefield and
inspecting the Royal Free’s records, The Lancet
issued a statement which concluded that Wakefield
should have disclosed his interest. He should have
told the editor about his study for the litigants and
its £55,000 funding, even if there had been no
children overlapping with the Lancet study.
“If
we had known then what we do now, we certainly would
not have published that part of the paper that
related to MMR,” the editor added. Wakefield had
another opportunity early on to set the record
straight. After the Lancet study appeared in February
1998, the Medical Research Council (MRC) convened a
meeting to discuss it. Numerous doctors and
professors were present, along with officers of the
MRC. Minutes of the meeting record: “How were
the patients selected? Members were interested in how
the children had come to be referred to the (Royal
Free) team, as this had a bearing on the issue of
bias.”
It
was an obvious moment for Wakefield to declare his
hand, to disclose his interest and put the record
straight before the MMR scare that the Lancet study
had sparked got out of control. But again he failed
to reveal the legal aid contract.
Professor
Sir David Hull, chairman of the government’s
joint committee on vaccination and immunisation, was
present. “Certainly the fact that these patients
were litigants would be relevant to interpretation of
the data,” he said. “It was already very
questionable whether anyone seriously looking at the
data would draw the same conclusions as
(Wakefield).” Ironically — and to much less
fanfare — Wakefield published a few months later
a little noticed study that revealed just how skewed
his original Lancet study had been. The brief
synopsis, published in a journal called Gut, had data
on the original 12 children of the Lancet study and a
further 18. Parents of only three of the new children
attributed the onset of their children’s
behavioural problems to MMR. Put another way, the
incidence of parental association between MMR and
autism had dropped from 66% to just 12%.
Did
this undermine the Lancet findings? “You may be
right,” Wakefield said last week. “I simply
don’t know. It does seem that as we examined
more numbers the percentage of parents who ascribed
(their children’s problems) to the vaccine fell
away.”
EVER
since the BSE scare, when the government first
declared beef to be completely safe but then decided
that it could kill, the public has been distrustful
of the health authorities. When Wakefield and The
Lancet published his study in that climate, the
public was ready to disbelieve government protests
that MMR was safe. “After (the study) first came
out we were struggling just to get parents to
immunise their children,” said Dr Michele
Hamilton-Ayres, a consultant paediatrician in
Cheltenham. “Things got terribly bad.”
Immunisation
rates have fallen dangerously low and the incidence
of measles cases has risen sharply. Meanwhile, legal
cases have proliferated: since Wakefield and Barr
were granted the £55,000, legal aid for those suing
the vaccine companies has reached £15m. Of that,
about £5m has gone to Barr’s present firm,
Alexander Harris, and about £4m has gone to doctors,
some earning £100 an hour to study reports.
The
Legal Services Commission (successor to the Legal Aid
Board) cut off funding last year, but lawyers
pursuing compensation claims have taken that decision
to judicial review.
Wakefield
remains unrepentant. He insists that he and his
colleagues have discovered a novel bowel disease in
some children with developmental disorders. He
claimed last week that the £55,000 study, finally
submitted for publication, has found “live”
measles in the guts of children with behavioural
disorders. But even he admits that this is all a long
way from proving that measles, let alone MMR, causes
autism. No causal link has been found between them.
Is he
embarrassed? Would he like to apologise? Last week,
after these questions were put directly to him, the
real passion that drives him suddenly broke through.
“Should we stop, should we go away, should we
stop publishing because it is inconvenient?” he
asked. “I’ve lost my job. I will never
practise medicine in this country again. There is no
upside to this. “But if you come in to me and
say, ‘This has happened to my child’,
what’s my job? What did I sign up to when I went
into medicine? To look after your child. How many
other children does this affect because your
child’s expendable if it’s only your child
(suffering damage). That’s not my job. I’m
not here to make that kind of decision. I’m here
to address the concerns of the patient. There’s
a high price to pay for that. But I’m prepared
to pay it.” His co-authors, however, feel
betrayed. “I am very, very angry,” said one
of them yesterday. “I would never have put my
name to the study if I had known there was this
conflict of interest, and had I not done so it would
never have got published.”
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