Near the start of last year, The Sunday Times ran some news and feature stories about the risks of a popular drug. To tell you the truth, they were unfashionable interventions in the chatter of modernity - stressing the product's controversial origins and associated injuries and deaths. And although they filled a good bit of space, like many inquiries into pharmaceuticals (going right back to the infamous morning sickness treatment Thalidomide) they were initially ignored by the rest of the press, and there seemed nothing more to be said.
The drug in question is an antibiotic (or, more correctly, an "antibacterial") known most commonly in Britain as Septrin (in the US as Bactrim, or Septra). It is a classic, world-wide blockbuster of a medicine, taken by one in three of the United Kingdom's population, prescribed more than 85 million times in England and Wales, and for the last quarter century scribbled on pads by general practitioners virtually as an all-purpose pill.
But within hours of the stories hitting the streets, a stream of calls began to pour down my phone - and has yet to come to an end. People call me at 8.30 in the morning to talk about Septrin. They call on Saturday nights. Some call asking how to spell "sulphonamide" while I drip after stepping from the bath. Others just feel the need to call someone - now and again to break down and cry. In fact, since the initial publication on the subject, I have talked to more people (including doctors, lawyers and politicians) about Septrin, than about the rest of my journalism combined.
The typical caller will be a woman saying that she had taken the pills (either for something important, like a urinary tract infection, or something trivial and often inappropriate, like a sore throat) and that it had pretty much destroyed her life. She will talk about such things as collapsing, comas, blowing up with football-size blisters, scarring to her eyes, multiple operations, organ failures, fatigue, depression, suicide attempts, inexplicable allergies, blood pressure fluctuations, pains travelling up her spine and "exploding" in her brain, immune malfunctions - and more.
"I've been in bed with this since 1976," is the kind of thing I've heard more than once.
In the first weeks, the callers were so like each other that it was hard to spot the joins. The phone would ring and somebody would recount their tale, and then, say, 40 minutes later it would ring and someone else would say the same. It felt like being trapped on a Mobius strip - that half-twisted, glued paper loop you did in maths, with only one edge and just one side. After writing about Septrin, my life became like your finger: going round and round and round.
From time to time, I hear other tales, most memorably about young children. There's a four-year-old South London boy, for instance, who was born with brain damage and no ears after his mother was prescribed the drug while pregnant. There is another boy in Cardiff, who, after taking the medicine at age 18 months, is now permanently intubated and according to his mother stops breathing several times a day.
There are more whose parents are sick with worry about their child's state of health or mind. There are families where three generations used the product and all say they suffered adverse effects.
Then there are accounts of horrific deaths that people phone to talk me through. An old woman in the North of England passed away in conditions of such medical negligence that her husband spoke of killing the doctor. A previously fit 31-year-old rugby player in Australia who took Bactrim (a different brand of the same drug) dropped more or less cold in the street. And a Sussex girl, aged 18, got her A' level results in the hospital where a few days later she died. "The noise the machine made became like a continuous note," her mother recalled, when I went to see her. "And then I knew she was gone."
I put many of the callers in touch with each other and as a result of their efforts (mostly those of a group formed in Buckinghamshire) more than 1,000 people have since come forward with stories like those I've heard. Probably for reasons of competitive disdain, newspapers never much bothered to pick up my interest, but ITV's News at Ten and BBC2's Newsnight eventually gave the story a spin. And each time the word "Septrin" has been raised in the media, my phone starts jangling again.
"I was told that I was one in a million," has been the strongest common thread. "I thought there was only me, until now."
If you like bleeding heart journalism, there is grief enough here to fill a book. But as the months have passed a whole has emerged that is greater than the sum of the anecdotes. Go through official product information for almost any prescription medicine and you will see much the same kind of references to potential risks of adverse effects. What then becomes clear from these calls about Septrin is that behind all the wonder-drug hype journalists produce, there may also be something like a hidden epidemic of pharmaceutical casualties.
Of all those who called me, one of the people who sticks in my mind is a lady from East London called Kate Reid. She phoned shortly after my first piece appeared - and straight away won my heart. "You know what I did," she chuckled, in an accent I later discovered was polished in a Stepney children's home. "I rang round all the papers, and I asked for the medicine correspondent, and told them they were bastards."
She hated journalists, particularly those she had been writing to since 1987. Her own experience with Septrin was by no means the worst, but the problems she complained of after taking it aroused little more than PR sympathy. The now-axed comedy-and-caring programme, That's Life, for instance, wrote to her that the medical problems from which she suffered were "self-limiting" and "not life-threatening". The Sun's agony aunt suggested she see a counsellor to "release the anger", adding: "I am enclosing my own leaflet on nervous stress."
But Kate's anger was what grabbed me, even though she wasn't suffering nearly as badly as some. After taking Septrin for two days in August 1986, she spent six weeks in intensive care, needed two operations and four skin grafts, and now suffers from permanent fatigue, scarred eyes and bouts of depression.
But though others have fared worse (and, to be balanced, many much better) her response to misfortune has been so tenacious that she is top of an alternative league. More than anybody, she has shouted down every avenue and alley for a remedy or route to redress. More than anybody, her experience since being injured exposes how the epidemics remain concealed.
At the time she took the drug, she had just moved into a flat above a butcher's shop in Barking, Essex. She remembers acquiring the knack of sleeping through the sound of meat-chopping at dawn. She was then 30, divorced six years, and with a small mortgage that made the flat the first place she felt was truly her home. "It was somewhere I could start again, you know?" she told me one afternoon, while we sat on the floor and rooted through her case papers. "It was like the first time I was in control."
Things were also looking up on the relationship front. Since her marriage ended, she had worked as a telex operator for a Japanese bank and lived for nothing more keenly than package holidays at Mediterranean resorts. With a gang of girlfriends, she had visited Lloret de Mar eight times and Corfu once; drinking and dancing at all-night clubs and slapping down randy boys.
The August she took Septrin, she was leaving for the Greek island of Spetsai on her first holiday with a man. He was a broad-shouldered Underground guard called Kelvin, who she met while buying a kebab. On the Saturday morning before they were to due to go, she visited her local surgery complaining of thrush in her mouth (probably linked to an eating disorder). She was seen by a locum, who prescribed Septrin (known generically as co-trimoxazole). It was an eccentric decision, since thrush is a fungus, which is not treated by antibacterials. But Kate took the medicine and within hours of the first tablet began to get seriously ill.
At first, she lost energy, collapsing into lethargy, and by next morning her eyes were stinging. These proved to be early signs of a blistering and sometimes fatal allergic reaction called Stevens-Johnson Syndrome. In the last year of phone calls, I've heard of this a lot. It's association with Septrin is not disputed. A doctor was summoned to visit Kate at home, but once again, the treatment was wrong. Instead of spotting that she was suffering a reaction (and was at risk of coma), he prescribed an optical ointment, chatted her up, she says, and then continued on his weekend round.
"I was really lucky after that, though," she told me of how she came to be hospitalised next day. "Kelvin woke up about five o'clock on the Monday morning and he found I wasn't in bed. I'd gone into the bathroom, and I'd laid down on the floor. I felt like I was burning up and it was cool on the floor. And he came in and found me there. Saved my life, he did."
She was well cared-for during her weeks in hospital, but when she was sufficiently well to go home she found herself clobbered again. Inquiries revealed that her GP records for the incident were virtually non-existent (If I had a fiver for every person who has told me about their incomplete medical records...) obscuring the use of an antibacterial in an attempt to treat oral thrush. And, though she was quite sick, when she complained to the local doctors committee, the response was like the bite of a cornered ferret: she was struck off her doctor's list.
"It may help you to understand the position," the committee secretary wrote, "if I explain that, just as you have the right to change your doctor without having to give any reason, so a doctor has a similar right to have a patient removed from his list." Don't blink too hard, or assume it's unusual. During the last year, tales from the surgery have got so bizarre they are usually best passed-over. Victims have variously said that their GPs insisted that Septrin had no side-effects. They have told me that they were prescribed the drug even after reacting badly to it in the past. And most commonly they say that their suspicions about the drug were brushed aside in "I'm the doctor" style. Nobody has said they thought their mishap was notified to the government's watchdog: the Committee on the Safety of Medicines (which maintains its own list of 137 deaths and 6,000 notified injuries that may be linked to Septrin).
Kate's next move was to try to turn up the heat. She put her case in the hands of solicitors. "Com-pen-sation", of course, is the universal war cry of the aggrieved these days, from police officers who have witnessed calamities, to people who are wrongly nicked. So she thought that she had better get screaming too - less for personal gain than to warn others. With newspapers endlessly running DRUG VICTIMS TO SUE-type headlines, she assumed this was a way of alerting the public, and supposed others had got somewhere this way.
But she was quickly to discover that the legal process offered little to achieve her goals. Although product documents contain more than 100 lines of warnings about the potential risks of Septrin, when it comes to any one particular injured person, medicines and their prescribers are always reckoned blameless unless cause and effect can be proved. No number of similar complaints, like those of the thousand who have come forward after my stories, can be accumulated to make the case.
For Kate to succeed in suing the doctors, she would have to prove that they had acted unreasonably - a hopeless task without detailed notes. If she targeted the drug's manufacturer, she would not only have to prove that its product caused the injury (and wasn't just co-incidental to it), but also that the firm was reckless or negligent in bringing the stuff to market. And apart from a few media-driven "admit nothing" settlements, like the deal to resolve the Thalidomide catastrophe, this cause and effect plus culpability hurdle has never been cleared in Britain.
Kate, nevertheless, trudged down both paths, determined to make what progress she could. First a firm of lawyers ordered medical reports for an action against the doctors, who shouldn't have prescribed the drug for thrush, and should have recognised the adverse effects. But legal aid was withdrawn because she couldn't stand it up. She couldn't prove the doctors were at fault. Then, last year, another solicitor got her hopes up with a plan to go after the manufacturer. "I'll try anything," Kate told me. "I've just got to keep trying."
Solicitors just keep trying as well: it is essential for the system to work. In the last big side-effects case (over tranquillisers), lawyers and their medical experts grossed an astonishing £30m from the legal aid fund in an action that was abandoned as hopeless. Thousands of alleged victims, meanwhile, got zilch (less years of wasted effort and stress). Over Septrin, some solicitors are placing advertisements for customers in local newspapers, while others have instigated what they call an "action group" in a bid to channels clients to themselves.
These firms argue that the drug was poorly tested. But while probing this claim would be lucrative for lawyers, it's a blind alley for plaintiffs like Kate. If anything, when Septrin was launched (in 1969), its ingredients had been rather over-researched, compared with some medicines - and the side-effects were forecast from the start. Its formulation was considered so uncontroversial that the inventor, George Hitchings (who won a Nobel Prize), told me that he had finalised the product's specific formulation during a train ride from Zurich to Basle.
His confidence sprang from the fact that Septrin is not just an antibacterial, but rather two mixed together. And the one which probably has the worst side-effects profile - a compound called sulphamethoxazole (in the US: sulfamethoxazole) - had not only been around for donkey's years, but was among the massively prescribed sulphonamide class of bug-busters that dated back to the 1930s. They were actually an offshoot of chemical colorants whose therapeutic properties were accidentally discovered from their effect on dye-workers' skin complaints.
The other component - called trimethoprim - is safer than its partner, according to published research, although its pedigree goes back to mustard gas. It kills bacteria at least 10,000 times more effectively than it does human cells, so, the theory has it that if you don't use too much of it you shouldn't suffer any adverse effects.
Both compounds operate by blocking the sythesis of folic acid, at different stages, and it was assumed by the developers that combining them together would yield some synergistic benefit. But in almost every situation in which Septrin is used (mostly urinary tract infections, bronchitis and other common complaints) little-publicised research shows that this is not the case: trimethoprim alone would do the job. Using both together to zap a bug is like stabbing a person with a knife who somebody has already shot to death.
But some firms make knives and others make guns - and pharmaceuticals is an industry (mostly a branch of fine petrochemicals) with products it needs to sell. The two components belonged to different companies: one of which was a giant, Hoffman-La Roche, with vast production and marketing set-ups, while the other, the smaller Wellcome organisation, which had the patent on the new and better drug. So they pooled their strengths in Septrin (Bactrim, Septra, co-trimoxazole) and ran a massive campaign to persuade doctors to prescribe it. The ageing sulphonamides got a fresh lease of life. The new drug saw the light of day. Both firms made a lot of money: more than $5bn in world-wide sales.
But there was one important snag: the side effects of the combined product were bound to be more severe than one or the other alone. A circular issued by the Committee on the Safety of Medicines in the year before Kate was injured showed that the number of deaths (at least those they knew of) associated with the combined tablet was nearly eight times greater per million prescriptions than those linked to the antibiotic, ampicillin.
Kate was outraged when she learnt all this. And also, at times, depressed. Back in 1986 she, like others who told me their stories, thought that she was merely one in a million. Emotionally it felt like being injured in a car accident: just one of those unlucky things. But now she wondered if the driver was sober, and if the car was fitted with brakes. If anything, learning the facts made her feel worse than before. "How is it they can do this?" she asks me today. "Why? It doesn't make sense."
In her anger for answers, she opened another front: putting her questions in the hands of politicians. Over the past year, scores of Septrin casualties have contacted members of parliament - a few of which have written to ministers or expressed their personal concern. But most have been satisfied get local newspaper publicity of the "MP DEMANDS INQUIRY" sort. Kate, however, was determined to create hell and nagged her constituency's Labour incumbent, Margaret Hodge, into calling a brief parliamentary debate.
On March 22, a dozen Septrin casualties trooped with her to the Commons, chattering excitedly about the progress they felt that the political process might make. "I thought that now we were going to get some answers," she says. "I mean, this is where the government and everybody is, and I thought: 'If they can't explain it, then who could?"' Only six MPs came for the brief discussion in the chamber, but Kate and her supporters clapped wildly in the gallery when her representative got up to speak.
But then politics failed her just as comprehensively as she had been failed by medicine and the law. Her MP could not really be said to be on top of the issue, and on the government benches, drowning in a sea of empty green leather, a junior health minister, Tom Sackville, promptly announced that officials had denied any knowledge of a problem. The "pattern of adverse reactions" was the same with all antibiotics, he read out. A one-ingredient tablet would need "much larger doses". Trimethoprim alone "leads to greater resistance" among bacteria. "What we have to be clear about," he said, "is whether co-trimoxazole has a higher level of risk than antibiotics generally. The evidence that has been given to me is that this is not the case."
Looking back at those words, printed in the parliamentary minutes, Hansard, I feel like James Stewart up the bell tower in Vertigo.What Sackville had parroted to MPs was not only contradicted his own department's statistics, but by basic reference books on the shelves of every doctor, decades of published research and product documents published by drug companies where every comma is scrupulously checked. That the two drugs together were more dangerous than only one of Septrin's ingredients was a simple, unarguable, fact.
While the minister dissembled in the Commons, moreover, doctors had abandoned the cause. The former chairman of the Committee on the Safety of Medicines, Sir William Asscher, told Newsnight that the drug's use should be sharply curtailed. Dr John Griffin, a former health department official and the past head of the Association of the British Pharmaceutical Industry, declared that it probably wouldn't get a license today. And although at its peak in the 1980s Septrin had been prescribed an average of four times a day by every general practitioner in Britain, Central Television was forced to cancel a studio debate because none would come on camera to say why.
But it's not that the minister was talking garbage that caused my sense of unease. (As it happens, other Septrin victims had already been dismissed by the health secretary, Virginia Bottomley, who wrote to another backbencher last October that "direct comparisons between these medicines cannot be made.") What was so weird about the Commons event was that it proved that the system was not capable of coherence in the face of Kate's one-woman campaign. It was like an error message appearing on a computer screen, revealing some malfunction within.
To me, that's what this story is all about: a warning of things unseen. Lurking behind the minister's statements is a system which has kept side-effects off the public agenda, but allows hidden suffering to continue. And while doctors, lawyers, politicians, and even journalists, dip into such matters from time to time - giving the reassuring impression that remedies are at hand - they often become invaluable players in obscuring how things have gone wrong.
To understand what has happened, you could return to the 1960s and the uproar caused by Thalidomide. In those days, the pharmaceutical industry was wholly unregulated, with no medicine licensing, or standard-setting: a complete commercial free-for-all. But the political heat from hundreds of babies being born with terrible handicaps after their mothers took the product, led to the first-ever controls. In 1971, these came into effect in a Medicines Act, which sought to guard against the most spectacular calamities, but in effect did a trade-off on the rest.
Firms had to show that their medicines had some benefit and did not carry intolerable risks. A scheme was launched to allow GPs to report side-effects to a central register. And a review was begun through which nearly forty thousand marketed medicines were whittled down to 5,300. But these arrangements were to be controlled by the industry itself, and although watchdogs were set up - including the Committee on the Safety of Medicines - their memberships were packed with drug firm executives, contract researchers, and shareholders. Typically, at a meeting with 20 people present, only three or four are not payrolled in some way.
There's no better proof than the calls I get on Septrin that this arrangement has a life of its own. Experts (often the government's own) have shown that medicines can easily be compared with others for their usefulness and withdrawn if they fail. Monitoring would cost a few hundred thousand pounds a year to watch over product safety. Compensation schemes could provide financial help for those who are casualties of adverse events. But these would all tease out the true risks. And the system, it seems, can't handle that.
Whether the post-Thalidomide accommodation is as resilient as it appears, however, is a question that Kate is still testing. She says she is far from finished with her battle, and each defeat makes her more furious. "The thing is there's lots of people coming forward and they have all been told that they are one in a million, and that isolates them," she says. "Do you think I'm going to stop? No. Because somebody has got to be made accountable for what's happened - to my life and to other people's lives."
She doesn't talk a lot about her own situation - partly I think, because she finds it hard to discuss with a man some aspects of her problems. She sometimes mentions a desire to adopt children - revealing, in passing, that her internal injuries have left her unable to give birth. She did once tell me about Kelvin walking out, yelling at her in a rage, "You can't do anything for me any more". But then she changed the subject to her crusade.
Her next plan is to get victims to band together for a campaign of direct action. After being let down by doctors, lawyers and politicians, she reckons that the only course left for her is to bring the Septrin battle "to the streets". During the House of Commons debate, she and some of the others who turned up to listen vowed to target those who ought to help but don't. Top of their list is the London headquarters of the British Medical Association, where they have plans to trespass until a doctor is produced to explain how they can improve their health.
"I mean there are so many answers that people want that nobody will give them," she says. "Suppose we go down the BMA and say we ain't leaving till we see a doctor? What are they going to do? They've got to listen."
In the year that I have listened, the casualties of Septrin have more and more talked in such terms. Kate has even thought through the consequences of such an action, when the staff at the citadel of medicine pick up the phone to call the police to clear them out. "What are they gonna nick you for?" she laughs. "The people who are going to nick you have probably got a wife and children, and he'll probably go home and tell his wife: 'Don't take Septrin'."
As for me, I won't trespass. I'm a watcher, not a doer. Like doctors, lawyers and politicians, our role is to do a job, but not get involved. Maybe I will just hang around here and wait for the phone calls. A sense of action without taking risks. The calls are calming down now (with a flurry yesterday when Kate appeared on Good Morning with Anne and Nick). And to be honest, I dread the thought that the call-after-call sessions will soon start up again.