Is the MMR vaccine a cause of
autism - or is it a vital health programme

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Report By Robert Sandall for The Sunday Times Magazine.

A conspiracy of silence or paranoid scare mongering? Is the MMR vaccine a cause of autism - or is it a vital health programme undermined by this medical maverick? In March, seven mentally disturbed British children and an escort of parents, two doctors and three lawyers flew to Detroit, Michigan, for a medical test that had been denied them in the UK. The procedure, a lumbar puncture to extract specimens of cerebral spinal fluid (CSF), is uncomfortable and requires anaesthetic - but it is routinely carried out in advanced western countries in the treatment of many chronic ailments, such as leukaemia. In the cases of these children, all of whom were prone to seizures as well as a range of self-harming antics, an analysis of the liquid that bathes the brain had been separately recommended by two neurologists.

Over the course of a year, the 246 private and NHS hospitals in Britain equipped to carry out CSF taps had declined to touch them, usually on the grounds that the test amounted to human experimentation, not treatment. In November 2002 one hospital briefly assented before putting the matter before its ethics committee, which decided four months later not to proceed for the same reason: the children were being used as guinea pigs.

It was an arguable point. Before an illness can be treated, it must be fully understood, and the root of these children's problems hadn't been ascertained. By the time a hospital outside Detroit agreed to accept them in March, their parents and advisers were worrying that the tests would never take place. They were nearly proved right.

On the night before the children arrived at the hospital, lawyers acting for GlaxoSmithKline (GSK), Merck and Aventis Pasteur MSD, manufacturers of the MMR triple vaccines that have been used in the UK since 1988, approached a High Court judge in London for an injunction to prevent the CSF taps going ahead. Two of these combination jabs had been called into question before: Pluserix, by Smith Kline (pre-Glaxo), and Aventis Pasteur's Immravax were withdrawn in 1992 after the "urabe" strain of mumps virus used in them was deemed responsible for a meningitis outbreak by the health authorities in Canada. That strain was replaced and M-M-R II, patented by Merck but licensed to GSK, became the triple jab most often offered in the UK. Now the possible misbehaviour of the measles component was at issue. The drug companies wanted a delay because their medical representative needed to be present at the procedure, but couldn't get to Port Huron, Michigan, in time. The injunction, however, was denied.

The children were the claimants in a "class action" - legal-speak for a case launched jointly by victims with the same grievance. If successful, it would validate the claims of 1,300 other British families and trigger international damages awards that could top $1 trillion. The proposed test, to look for traces of measles-vaccine virus in the children's CSF, could provide evidence that it can pass from the gut's lining into the brain, where measles is known to affect cerebral processes.

This is one of the most contentious issues in the row about what, if anything, brings on a disease described, but not universally accepted, as "autistic enterocolitis". In the UK, the condition was first identified by Dr Andrew Wakefield, but scientists in Japan, Norway, Ireland and the US (including Buie, Winter and Kushak, based at Harvard) have also published research supporting a link between intestinal disease and autism.

The theory that a malfunctioning or "leaky" gut sends partially digested food - in the form of opioid compounds known as peptides - up to the brain is one of the less controversial aspects of the hypothesis under investigation. Whether measles vaccine is what gives rise to the gut disease in the first place is the trillion-dollar question. So far, the sum of Wakefield et al's discoveries has not met the exacting medical standards that establish causation. All it points to is an "association". But the importance of the spinal-fluid link was well understood by the defendants in the class action. Merck's QC had recently referred to it in court as "a significant result when trying an issue as to whether or not MMR vaccine causes autism".

Time was running out for the claimants. Their action was being financed by the Legal Services Commission (LSC), a successor to the Legal Aid Board, which had set a July deadline for the submission of expert medical evidence, after which funding would be reviewed. Having lost a year trying to get the CSF samples in the UK, they now had to fly seven severely autistic, occasionally violent children - most of whom had never been in a plane before - halfway round the world.

. . .THESE INTERVENTIONS MIGHT, JUST MIGHT, HAVE BEEN ORCHESTRATED TO DELAY DELIVERY OF THE SAMPLES, ALLOWING THEM TO SPOIL. SO WHEN THE VIROLOGIST IN THE PARTY, COLIN FINK, GOT THEM BACK TO HIS PRIVATE LAB, MICROPATHOLOGY, IN COVENTRY, HE TOOK THE UNUSUAL PRECAUTION OF PLACING AN ARMED GUARD OUTSIDE OVERNIGHT.

Another bid by the defendants to secure an injunction, this time in the US, also failed. Then the hospital called the British party in Detroit to cancel their appointment.

Although lumbar taps on autistic children are common in the US, this batch, Lansing hospital now felt, constituted unwarranted human experimentation. But the children's camp had an undisclosed back-up plan. They had made an arrangement with another hospital in Port Huron, two hours along the shore of Lake Michigan, and this time, despite further delaying tactics from the lawyers in London, the CSF taps went ahead. One of the seven children reacted badly to the anaesthetic and couldn't be tested; the other six were fine.

Now the party and the fluid samples had to be flown home for analysis. There was bedlam on the bus as the anaesthetic wore off: one child tried to exit the moving vehicle by the back door, while another was restrained by his mother in the toilet. At the airport, the container of dry ice carrying the CSF was deemed too large to be carried on as hand luggage, and another business-class seat had to be specially purchased for it.

After the KLM flight had boarded, five US customs officers arrived to take the lawyers and doctors off the plane - the only passengers they apprehended - for separate, 30-minute taped interviews. They weren't asked any questions pertaining to passenger safety and their large container: the issue was why the children hadn't been tested back in the UK. In transit at Schiphol airport in Amsterdam, they were again singled out for more questioning.

By now, several tired minds were stoking their paranoia that these interventions might, just might, have been orchestrated to delay delivery of the samples, allowing them to spoil. So when the virologist in the party, Colin Fink, got them back to his private lab, Micropathology, in Coventry, he took the unusual precaution of placing an armed guard outside overnight.

The next day the CSF samples were couriered to their final destination: Professor John O'Leary's laboratory at Trinity College in Dublin, a facility whose viral-testing kit had previously identified the DNA of measles in the guts of autistic children. Rather disconcertingly, the package appeared to have been opened en route, but with the war in Iraq only two days old, customs everywhere were on high alert.

The analysis proceeded: three of the six samples tested positive for the vaccine strain of measles virus, but only in minuscule genetic fragments - and not enough to count as a valid research sample. According to medical-research protocol, that result had now to be compared to the CSFs of a "control" group of non-autistic patients. Acquiring these took several months, during which the claimants missed the LSC's July deadline and had their funding temporarily suspended awaiting an appeal on September 30.

When the doctors finally assembled their evidence, the children's lawyers felt confident. Only 1 in 20 of the control group - all leukaemia sufferers, specifically chosen for their high susceptibility to random viral infections - was found to be carrying measles virus in their CSF.

The defendants' analysis of the same samples, carried out by Dr Peter Simmonds at Edinburgh University, had found no trace of measles in the children's CSF. But Simmonds had chosen to use a different viral tracker, Nested, rather than the claimants' TaqMan process. Given the accepted centrality of findings in this area, they felt that their case against MMR looked strong enough to take to court in April 2004. But the four adjudicators on the LSC's funding-review committee disagreed with them. Justifying the �15m already spent as having served the "wider public interest", the committee stated that the �10m needed to see the action through "would not prove a link between MMR vaccine and Autistic Spectrum Disorder".

The claimants' lawyers suspected that the committee had made up their minds before considering the CSF test results, as these offered fresh evidence of just such a link. At the hearing, they were told to await a decision at the end of the day, and written reasons for it two days later. But if the answer was yes, they wondered, why would the reasons not be immediately forthcoming? They were not reassured to discover, when they looked more closely, that the LSC's e-mailed press release dropping the case had been originated the day before the hearing.In a footnote to editors, the LSC admitted that its decision reflected a change of policy rather than an assessment of evidence. "In retrospect it was not appropriate for the LSC to fund research. The courts are not the place to prove new medical truths." That judgment is itself up for judicial review in the new year - though the LSC is not bound to accept its recommendations.

Paranoia is currently the default mood on all sides of the MMR debate. The British government is so scared of it that health ministers will not be interviewed on it. The drug companies are on the defensive against damages claims that, if proven, could seriously undermine their credibility and their business. And the anti-MMR lobby is convinced a coalition of government agencies, the medical Establishment and big pharma are against them, X-Files style.

In a leafy southwest-London suburb, the man whose 1998 paper in The Lancet kicked off the fracas, Dr Andrew Wakefield, would prefer not to talk on the phone. He believes his line was tapped about three years ago, and now conducts regular "sweeps" to check it for bugs.

Visiting the house whose garage has served as his office since he resigned his post at London's Royal Free hospital in 2001, it strikes you that Wakefield can't be doing this for the money. From the outside, his house looks as if it might be the only squat in an otherwise tidy, middle-class road, its overgrown front garden dominated by a tree stump curiously carved into a V-sign (a message to the former chief medical officer, Sir Kenneth Calman, he later tells me). Unlike many of the activists in the anti-MMR camp, Wakefield is a man unscarred by family tragedy. His four children, the eldest of whom is 13, are as fit as fleas, tearing around the house and back garden. All have had vaccinations, he says, though not the MMR jab. As he first said in public in 1998, he's a one-at-a-time man where vaccination is concerned.

UP UNTIL 1998, WAKEFIELD HAD BEEN A WHIZ-KID. HIS DISCOVERY THAT AN INFLAMMATORY BOWEL DISEASE, ULCERATIVE COLITIS, CAN BE BROUGHT ON BY ARTERIAL PROBLEMS RATHER THAN, AS WAS PREVIOUSLY ASSUMED, BY A GUT FULL OF GERMS, MADE HIS NAME.

In appearance he's like a genial fly half, solidly built, with hooded, watchful eyes, a boyish grin and an easy manner. What bothers him most, he says, is the way his research has been rubbished by colleagues who deny gut treatment to children who, he believes, badly need it. On his laptop is a photograph of Laurence, an autistic boy with a severely distended belly, whose mother has been accused of starving him and was refused access to a paediatric gastroenterologist. Next to Laurence in the picture stands his healthy, unstarved sister. This is a classic case of autistic enterocolitis, says Wakefield. "He's clearly sick. That boy and his mother are being maltreated by the medical Establishment." Such vehement declarations don't endear him to many of his former colleagues.

Wakefield feels pretty maltreated himself. Since qualifying in 1985, he has published 128 papers in "peer-reviewed" journals, articles that are read and assessed for their scientific credibility by an independent panel of up to five experts before being printed. His CV is a wodge of impressive titles and tricky acronyms: The Lancet, JAMA (The Journal of the American Medical Association). He has published 49 papers on aspects of autistic enterocolitis, the most recent in November's Journal of Clinical Immunology.

Wakefield's big beef is that his clinical findings haven't been properly challenged on their own terms. He conducts or collates the results of colonoscopies and biopsies of particular children. He calls this "scoping the kids". His opponents take a different tack: some have failed to replicate his findings using different clinical procedures and technologies. Others say his samples are too minute, anatomically and numerically, and examine the statistical incidence of autism versus uptake of MMR, and any adverse aftereffects. Study after study has found no correlation. Research published this year in America found a "statistically significant" risk of autism in cases reported 5 to 10 days after MMR, but in general the statistics suggest that Wakefield is making a mountain out of a molehill.

But the way this data is compiled and analysed is troubling. In Britain, the reporting of bad vaccine reactions is down to parents and harassed GPs, who have to fill out and forward yet another form to a national database, the so-called "yellow-card" system. Big studies abroad, in Finland in 1998 and Denmark last year, found nothing to worry about. But a similarly reassuring analysis in the US, published in the November issue of Pediatrics, has started a firestorm in Washington. A transcript of a conversation at the federal Center for Disease Control and Prevention (CDC), obtained under the Freedom of Information Act, revealed officials admitting that data on MMR could be manipulated to prove, or disprove, anything. The US representative Dave Weldon, a qualified doctor himself, wrote an open letter to the head of the CDC, noting its "selective use of data" and pointing out that the lead author of the study left the CDC two years ago to work for GlaxoSmithKline.

Wakefield, too, has taken a bit of stick from public officials recently. "Junk science" - a term used earlier this year by a High Court judge awarding in favour of a suit brought by two estranged husbands against their wives' decision not to give the triple jab to their children - particularly rankles. Why wasn't he called as the expert witness for the defence, rather than Jayne Donegan, a homeopath and GP from south London, he wonders. (Donegan was reprimanded by the judge for not answering the court's questions.) "It was a disgrace. We've published a lot on this in eminent journals. The first we heard of that case was when it was thrown out of court."

Life was different before he and six of his Royal Free team published their Lancet bombshell, the unexplosively titled "Ileal-Lymphoid-Nodular Hyperplasia, Non-Specific Colitis and Developmental Disorder in Children." Up until 1998, Wakefield had been a whiz-kid. His discovery that an inflammatory bowel disease, ulcerative colitis, can be brought on by arterial problems rather than, as was previously assumed, by a gut full of germs, made his name. It also established his modus operandi. As a trained surgeon, he based his research on observation rather than textbook precedents.

Wakefield's next hypothesis was more controversial: the presence of measles virus in the wrecked intestines of sufferers of Crohn's disease - a finding that was not replicated in worldwide studies set up by the World Health Organization in 2000 - led him to his first brush with big pharma. His co-funders, Merck, pulled out just before he published in 1996. Though he had previously received half a dozen research grants, totalling around $500,000, from Glaxo and Hoffman-LaRoche as well as Merck, his drug-company funding now disappeared. So he recruited a medical fundraiser, Robert Sawyer, to tap alternative philanthropic bodies, and ploughed on looking for gut measles. When Rosemary Kessick, the mother of an autistic child, came to him convinced her son's problems were related to the chronic diarrhoea he developed after having the MMR jab, Wakefield listened and looked.

WAKEFIELD HAD COOKED THE EVIDENCE BY CONCENTRATING ON JUST 12 CASES. HIS RESEARCH FACILITIES WERE CONTAMINATED. HE COULDN'T REPLICATE HIS OWN RESULTS.

Conventional diagnosis attributed the concurrence of autistic behaviour and severe bowel problems to coincidence, or held that disturbed minds naturally led to upset tummies. Wakefield wondered if the reverse might be true. Could "leaky guts" play a role in developmental problems? And if so, could these problems be alleviated by addressing the inflamed intestines? Other specialists regarded autistic children as medically untreatable, and none of Wakefield's business: he was a gut man. But the interventions he proposed seemed to work. Among the 200 or so children he oversaw, on average four times a year each at the Royal Free, their behavioural problems appeared to subside, though not disappear, as their guts healed. "These kids were often in extreme pain, and that was why they were screaming or banging their heads on the wall."

In the 12 cases that he and his team examined in detail, the children's bowel problems coincided with evidence suggesting that measles was lurking in the intestinal wall. Given the known propensity of measles to linger in the gut and, in extreme cases, to attack the brain, might this implicate MMR in their children's autism? It was, to put it mildly, an awkward question. Wakefield had already raised eyebrows by treating patients traditionally cared for by psychiatrists, virologists and community paediatricians. One of the latter had complained in a letter to a colleague in 1987 about "a zealot surgeon who thinks that MMR is the cause of all the problems in the western world". Now others accused him of over-egging the Lancet article. "Anecdotal reporting of a biased sample,"one complained. "This has no place in a peer-reviewed journal."

And soon the fur started to fly. Wakefield had cooked the evidence by concentrating on just 12 cases. His research facilities were contaminated. He couldn't replicate his own results. The last of these charges was true enough. For the first few years, his research results were inconsistent and contradictory. He blames this on the measuring technology. He says that changed in 1999 with Professor John O'Leary and his TaqMan viral detector, a machine sensitive enough to pick up minute traces of measles vaccine DNA in 75 autistic children with disorderly bowels. O'Leary has refused to finger MMR but he has demanded "extensive and immediate investigation" into the link. The presence of vaccine-strain measles, as opposed to the "wild" variety, O'Leary referred to as "a smoking gun".

The Department of Health (DoH) was not impressed. Despite Wakefield's submissions to the then chief medical officer, Kenneth Calman, six months prior to publication of the 1998 Lancet article, public-health officials were understandably resistant to a hypothesis that queried their vaccination programme on the basis of one small group of children in north London. But not as resistant as the drug companies who, as they generally do in teaching hospitals, sponsored a large chunk of the Royal Free's research. Everybody, Wakefield and co included, agreed that more studies were needed before MMR could be shown as a cause of autism. Not everybody, though, was urging that these should take place.

"THE SCIENTIFIC ARGUMENT ON MMR AND AUTISM IS OVER: MMR VACCINE IS NOT INVOLVED". HE URGED THE SUNDAY TIMES TO "DO SOMETHING POSITIVE" FOR MMR AND FOR CHILDREN WITH AUTISM, INSTEAD OF "ANOTHER HALF-BAKED PANAGYRIC [SIC] FOR JUNK SCIENCE". -BRENT TAYLOR

In its 1988 HMSO Handbook of Vaccination for Practitioners, the DoH claimed a 95% protection rate for the rubella-and-measles single jabs. In its 1996 edition, post-MMR, the measure of effective measles immunity had dropped to 90% - beneath the threshold guaranteeing "herd immunity". But by now the DoH's data-collection system no longer recognised single jabs in the compiling of individual health records. Today we are informed that MMR is more effective than single vaccines, as well as unimpeachably safe. But government ministers are reluctant to address the issue in detail, preferring to issue bland reassurances such as the one the health secretary, John Reid, made on GMTV in November: "It is unequivocal that there is no evidence at all that MMR is linked to autism." Off the record, however, DoH media briefers acknowledge that MMR has become "too political". After receiving wobbly guidance on poisoned eggs, mad-cow disease and the anti-arthritic drug Opren, the public no longer believes elected politicians on health issues, so comments on MMR are kept to a minimum. David Salisbury has presided over all vaccination programmes for the past 15 years, and currently advises the junior minister for public health, Melanie Johnson.

Neither of them would speak to me about a successor to MMR that was first revealed in the press in 1998, shortly before the Wakefield paper. This was MMRV - V as in varicella, or chickenpox. The DoH now denies any interest in this, possibly because research on MMRV has shown it doesn't work. A study partly funded by GlaxoSmithKline, published last year by the University of Melbourne, found that quadruply vaccinated children were more prone to suffer fevers immediately afterwards than those given MMR and varicella vaccines separately. Worse, they did not develop a significant immunity to chickenpox after 60 days. But the drug companies haven't given up: recent press reports tell of more tests on MMRV proceeding in Sheffield. The DoH says it is "not aware of such a product being available for use in the UK". The row about MMR derives in part from a chronic uncertainty as to what autism describes. A year after it was identified in 1943, by Leo Kanner in a study of 11 profoundly uncommunicative, unruly children, a variant - Asperger's syndrome - proposed a less serious version, in which poor social skills are offset by an obsessive attention to detail that can lead to high academic performance. For years, autism was thought to be caused by unloving parents, and "refrigerator mothers" in particular. In the 1960s it was redefined as an inherited brain disorder, and then came a distinction between classic congenital autism and a regressive variety acquired after the age of two.

Autism is now referred to as a spectrum disorder, a catch-all syndrome whose symptoms range from semi-suicidal lunges out of windows to a relatively harmless obsession with order and routine. Wakefield's theories about leaky guts blur definitions further by challenging the traditional view that autism is a purely psychiatric problem, and arguing that it can be treated by medical means as well as by behavioural therapies. One thing that is apparent is that there is a lot more of it about nowadays. We all know, or know of, somebody with an afflicted child. Authors, notably Nick Hornby, whose ex-wife Virginia used to be a trustee of Visceral, have written about their experiences as parents. Official statistics from the Medical Research Council (MRC) in 2001 revealed the rate had shot up from 1 in 5,000 per head of population in 1970 to 1 in 165. In 1988, when MMR was introduced, it was 1 in 2,200.

That might be coincidence, and it might be that as the spectrum of the disorder has broadened, we've got better at spotting it. Wakefield's former colleague at the Royal Free, Professor Brent Taylor, last year published a statistical analysis of children in north London showing that an autism epidemic was well under way before MMR. Then it was pointed out by Wakefield and Montgomery that many children in the survey who appeared, from their date of birth, not to have had the triple jab but who still developed autism, might have been included in an extensive "catch-up" MMR campaign targeted at older children in the early 1990s. Taylor later acknowledged this in a letter to The Lancet, but stands by his broad findings. In response to my request for clarification, he replied that "the scientific argument on MMR and autism is over: MMR vaccine is not involved". He urged The Sunday Times to "do something positive" for MMR and for children with autism, instead of "another half-baked panagyric [sic] for junk science". I pressed him to explain what he meant by "junk science". He didn't mail me back.

Such reticence from the pro-MMR party does not inspire confidence. Nor do their efforts to identify alternative causes for the steep increase in diagnosed autism. The Medical Research Council was given �2.75m by the DoH last year to fund new research. So far, none of that money has been allocated, though 12 projects are, it says, "under consideration". No details could be supplied. Meanwhile a three-year study that the MRC commissioned in 2000 from the London School of Hygiene & Tropical Medicine has not yet reported. Two papers are being readied for publication, one assessing the rise in autism since 1988 and another looking at possible links with MMR. The scientist in charge, Professor Andrew Hall, has inspected the GP records of 1,000 children diagnosed as autistic and sent questionnaires to 400 parents. Since none of Hall's team has been near an autistic child, whatever he reports is unlikely to silence Wakefield and the "scopers". It's stats against case studies, the old apples-versus-oranges argument. Again. On the day the Legal Services Commission announced it was pulling out of the MMR class action, the DoH endorsed that, stating that "this draws a line" under the controversy. Some hope.

Tomorrow [Monday], Five is scheduled to screen a TV drama, Hear the Silence, with Hugh Bonneville as Andrew Wakefield and Juliet Stevenson as the mother of an autistic child battling to get heard by an unsympathetic gang of haughty specialists. It is a partisan account of the MMR story, so partisan that Five has organised a televised discussion afterwards to let the DoH answer back. At the time of writing, it had not agreed to take part. The most misleading impression given by the drama is its portrayal of Wakefield as a gallant loner. In October, I flew to Portland, Oregon, to attend a conference hosted by the American pressure group Defeat Autism Now! (Dan!), where Wakefield was one of 23 research scientists - all confirmed as anti-MMR - making presentations to an audience of medics and parents. The last speaker was Rick Rollens, formerly secretary to the California state senate, and the father of an autistic son.

He presented a torrent of statistics detailing an 800% increase in diagnosed cases of autism since California introduced MMR jabs in 1979 and made them compulsory, in line with a nationwide Clinton decree in 1993. The state's Developmental Services Agency now finds that just under half its clients are autistic, compared with the 3% it dealt with pre-MMR. The epidemic, Rollens said, was threatening to wreck care provision in the nearly bankrupt public administration of California. This was a depressing and biased presentation. But at least it dealt in what looked like hard facts. Shortly after returning from Dan!, I attended a public seminar in London that addressed the MMR/autism issue in ostrich-like fashion. It was hosted by the PR company Hill & Knowlton, whose clients includes the three drug companies that manufacture the triple vaccine, and it was introduced by an online magazine, Spiked, one of whose columnists, the east London GP Michael Fitzpatrick, led the discussion. The audience was chiefly composed of health professionals, DoH representatives and media types. Two things stood out.

One was the meeting's concern that anxieties about MMR had been hyped by our old enemy the media. The other was its refusal to address the evidence that aroused public distrust in the first place. For these people, immunisation was an incontrovertible religious doctrine. Fitzpatrick rubbished the work of Wakefield, whose research papers currently outnumber his own by 128 to 0, as a superstition on a par with astrology. When somebody mentioned the divergence of scientific opinion, Professor Brent Taylor interrupted, again announcing that "the scientific debate is over". Andrew Wakefield has no plans to belt up. More studies are in the pipeline - so, no doubt, are more allegations of cover-ups and conspiracies. If Wakefield is proved right, then we've been poisoning our offspring, avoidably, since his 1998 study. If he's wrong, then let's hear some intelligible evidence ASAP, so we can get MMR vaccination rates up - from 67% in the London area and under 80% across the country - to head off threatened measles epidemics. And single vaccinations need to be reinstated as an affordable alternative to the worrisome triple jab. A typical price for a private measles jab is �150. Having spent �3m on a TV ad campaign urging triple vaccination, with a prowling lion protecting its young - which didn't work - the DoH's current course is to carry on ignoring Wakefield et al. A low-profile series of educational road shows and advice sessions in the 20 areas of the country with the lowest take-up of MMR began in the summer. In London, the country's anti-MMR capital, these have been almost invisible.

Such a feeble defence of the status quo, and a blanking of public anxieties that might be misguided but are nonetheless genuine, may suit embattled drug companies and embarrassed government policy wonks. But it isn't going to silence the enemies of multiple vaccination - nor will it do much good for anybody's health.

NOTE: This is only being shown in the UK.

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