Part 3 (1/2)

That's not the only time a placebo benefit has been found at the more dramatic end of the medical spectrum. A Swedish study in the late 1990s showed that patients who had pacemakers installed, but not switched on, did better than they were doing before (although they didn't do as well as people with working pacemakers inside them, to be clear). Even more recently, one study of a very hi-tech 'angioplasty' treatment, involving a large and sciencey-looking laser catheter, showed that sham treatment was almost as effective as the full procedure. showed that patients who had pacemakers installed, but not switched on, did better than they were doing before (although they didn't do as well as people with working pacemakers inside them, to be clear). Even more recently, one study of a very hi-tech 'angioplasty' treatment, involving a large and sciencey-looking laser catheter, showed that sham treatment was almost as effective as the full procedure.

'Electrical machines have great appeal to patients,' wrote Dr Alan Johnson in the Lancet Lancet in 1994 about this trial, 'and recently anything to do with the word LASER attached to it has caught the imagination.' He's not wrong. I went to visit Lilias Curtin once (she's Cherie Booth's alternative therapist), and she did Gem Therapy on me, with a big s.h.i.+ny science machine that shone different-coloured beams of light onto my chest. It's hard not to see the appeal of things like Gem Therapy in the context of the laser catheter experiment. In fact, the way the evidence is stacking up, it's hard not to see all the claims of alternative therapists, for all their wild, wonderful, authoritative and empathic interventions, in the context of this chapter. in 1994 about this trial, 'and recently anything to do with the word LASER attached to it has caught the imagination.' He's not wrong. I went to visit Lilias Curtin once (she's Cherie Booth's alternative therapist), and she did Gem Therapy on me, with a big s.h.i.+ny science machine that shone different-coloured beams of light onto my chest. It's hard not to see the appeal of things like Gem Therapy in the context of the laser catheter experiment. In fact, the way the evidence is stacking up, it's hard not to see all the claims of alternative therapists, for all their wild, wonderful, authoritative and empathic interventions, in the context of this chapter.

In fact, even the lifestyle gurus get a look in, in the form of an elegant study which examined the effect of simply being told that you are doing something healthy. Eighty-four female room attendants working in various hotels were divided into two groups: one group was told that cleaning hotel rooms is 'good exercise' and 'satisfies the Surgeon General's recommendations for an active lifestyle', along with elaborate explanations of how and why; the 'control' group did not receive this cheering information, and just carried on cleaning hotel rooms. Four weeks later, the 'informed' group perceived themselves to be getting significantly more exercise than before, and showed a significant decrease in weight, body fat, waist-to-hip ratio and body ma.s.s index, but amazingly, both groups were still reporting the same amount of activity.*

- I agree: this is a bizarre and outrageous experimental rinding, and if you have a good explanation for how it might have come about, the world would like to hear from you. Follow the reference, read the full paper online and start a blog, or write a letter to the journal that published it. - I agree: this is a bizarre and outrageous experimental rinding, and if you have a good explanation for how it might have come about, the world would like to hear from you. Follow the reference, read the full paper online and start a blog, or write a letter to the journal that published it.

What the doctor says.

If you can believe fervently in your treatment, even though controlled tests show that it is quite useless, then your results are much better, your patients are much better, and your income is much better too. I believe this accounts for the remarkable success of some of the less gifted, but more credulous members of our profession, and also for the violent dislike of statistics and controlled tests which fas.h.i.+onable and successful doctors are accustomed to display. If you can believe fervently in your treatment, even though controlled tests show that it is quite useless, then your results are much better, your patients are much better, and your income is much better too. I believe this accounts for the remarkable success of some of the less gifted, but more credulous members of our profession, and also for the violent dislike of statistics and controlled tests which fas.h.i.+onable and successful doctors are accustomed to display. Richard Asher Richard Asher, Talking Sense, Pitman Medical, London, 1972 Pitman Medical, London, 1972 As you will now be realising, in the study of expectation and belief, we can move away from pills and devices entirely. It turns out, for example, that what the doctor says, and what the doctor believes, both have an effect on healing. If that sounds obvious, I should say they have an effect which has been measured, elegantly, in carefully designed trials.

Gryll and Katahn [1978] gave patients a sugar pill before a dental injection, but the doctors who were handing out the pill gave it in one of two different ways: either with an outrageous oversell ('This is a recently developed pill that's been shown to be very effective...effective almost immediately...'); or downplayed, with an undersell ('This is a recently developed pill...personally I've not found it to be very effective...'). The pills which were handed out with the positive message were a.s.sociated with less fear, less anxiety and less pain.

Even if he says nothing, what the doctor knows can affect treatment outcomes: the information leaks out, in mannerisms, affect, eyebrows and nervous smiles, as Gracely [1985] demonstrated with a truly ingenious experiment, although understanding it requires a tiny bit of concentration.

He took patients having their wisdom teeth removed, and split them randomly into three treatment groups: they would have either salt water (a placebo that does 'nothing', at least not physiologically), or fentanyl (an excellent opiate painkiller, with a black-market retail value to prove it), or naloxone (an opiate receptor blocker that would actually increase the pain).

In all cases the doctors were blinded to which of the three treatments they were giving to each patient: but Gracely was really really studying the effect of his doctors' beliefs, so the groups were further divided in half again. In the first group, the doctors giving the treatment were told, truthfully, that they could be administering either placebo, or naloxone, or the pain-relieving fentanyl: this group of doctors knew there was a chance that they were giving something that would reduce pain. studying the effect of his doctors' beliefs, so the groups were further divided in half again. In the first group, the doctors giving the treatment were told, truthfully, that they could be administering either placebo, or naloxone, or the pain-relieving fentanyl: this group of doctors knew there was a chance that they were giving something that would reduce pain.

In the second group, the doctors were lied to: they were told they were giving either placebo or naloxone, two things that could only do nothing, or actively make the pain worse. But in fact, without the doctors' knowledge, some of their patients were actually getting the pain-relieving fentanyl. As you would expect by now, just through manipulating what the doctors believed doctors believed about the injection they were giving, even though they were forbidden from vocalising their beliefs to the patients, there was a difference in outcome between the two groups: the first group experienced significantly less pain. This difference had nothing to do with what actual medicine was being given, or even with what information the patients knew: it was entirely down to what the doctors knew. Perhaps they winced when they gave the injection. I think you might have. about the injection they were giving, even though they were forbidden from vocalising their beliefs to the patients, there was a difference in outcome between the two groups: the first group experienced significantly less pain. This difference had nothing to do with what actual medicine was being given, or even with what information the patients knew: it was entirely down to what the doctors knew. Perhaps they winced when they gave the injection. I think you might have.

'Placebo explanations'.

Even if they do nothing, doctors, by their manner alone, can rea.s.sure. And even rea.s.surance can in some senses be broken down into informative const.i.tuent parts. In 1987, Thomas showed that simply giving a diagnosis-even a fake 'placebo' diagnosis-improved patient outcomes. Two hundred patients with abnormal symptoms, but no signs of any concrete medical diagnosis, were divided randomly into two groups. The patients in one group were told, 'I cannot be certain of what the matter is with you,' and two weeks later only 39 per cent were better; the other group were given a firm diagnosis, with no messing about, and confidently told they would be better within a few days. Sixty-four per cent of that group got better in two weeks.

This raises the spectre of something way beyond the placebo effect, and cuts even further into the work of alternative therapists: because we should remember that alternative therapists don't just give placebo treatments, they also give what we might call 'placebo explanations' or 'placebo diagnoses': ungrounded, unevidenced, often fantastical a.s.sertions about the nature of the patient's disease, involving magical properties, or energy, or supposed vitamin deficiencies, or 'imbalances', which the therapist claims uniquely to understand.

And here, it seems that this 'placebo' explanation-even if grounded in sheer fantasy-can be beneficial to a patient, although interestingly, perhaps not without collateral damage, and it must be done delicately: a.s.sertively and authoritatively giving someone access to the sick role can also reinforce destructive illness beliefs and behaviours, unnecessarily medicalise symptoms like aching muscles (which for many people are everyday occurrences), and militate against people getting on with life and getting better. It's a very tricky area.

I could go on. In fact there has been a huge amount of research into the value of a good therapeutic relations.h.i.+p, and the general finding is that doctors who adopt a warm, friendly and rea.s.suring manner are more effective than those who keep consultations formal and do not offer rea.s.surance. In the real world, there are structural cultural changes which make it harder and harder for a medical doctor to maximise the therapeutic benefit of a consultation. Firstly, there is the pressure on time: a GP can't do much in a six-minute appointment.

But more than these practical restrictions, there have also been structural changes in the ethicil presumptions made by the medical profession, which make rea.s.surance an increasingly outre business. A modern medic would struggle to find a form of words that would permit her to hand out a placebo, for example, and this is because of the difficulty in resolving two very different ethical principles: one is our obligation to heal our patients as effectively as we can; the other is our obligation not to tell them lies. In many cases the prohibition on rea.s.surance and smoothing over worrying facts has been formalised, as the doctor and philosopher Raymond Tallis recently wrote, beyond what might be considered proportionate: 'The drive to keep patients fully informed has led to exponential increases in the formal requirements for consent that only serve to confuse and frighten patients while delaying their access to needed medical attention.'

I don't want to suggest for one moment that historically this was the wrong call. Surveys show that patients want their doctors to tell them the truth about diagnoses and treatments (although you have to take this kind of data with a pinch of salt, because surveys also say that doctors are the most trusted of all public figures, and journalists are tlie least trusted, but that doesn't seem to be the lesson from the media's MMR hoax).

What is odd, perhaps, is how the primacy of patient autonomy and informed consent over efficacy-which is what we're talking about here-was presumed, but not actively discussed within the medical profession. Although the authoritative and paternalistic rea.s.surance of the Victorian doctor who 'blinds with science' is a thing of the past in medicine, the success of the alternative therapy movement-whose pract.i.tioners mislead, mystify and blind their patients with sciencey-sounding 'authoritative' explanations, like the most patronising Victorian doctor imaginable-suggests that there may still be a market for that kind of approach.

About a hundred years ago, these ethical issues were carefully doc.u.mented by a thoughtful native Canadian Indian called Quesalid. Quesalid was a sceptic: he thought shamanism was bunk, that it only worked through belief, and he went undercover to investigate this idea. He found a shaman who was willing to take him on, and learned all the tricks of the trade, including the cla.s.sic performance piece where the healer hides a tuft of down in the corner of his mouth, and then, sucking and heaving, right at the peak of his healing ritual, brings it up, covered in blood from where he has discreetly bitten his lip, and solemnly presents it to the onlookers as a pathological specimen, extracted from the body of the afflicted patient.

Quesalid had proof of the fakery, he knew the trick as an insider, and was all set to expose those who carried it out; but as part of his training he had to do a bit of clinical work, and he was summoned by a family 'who had dreamed of him as their saviour' to see a patient in distress. He did the trick with the tuft, and was appalled, humbled and amazed to find that his patient got better.

Although he continued to maintain a healthy scepticism about most of his colleagues, Quesalid, to his own surprise perhaps, went on to have a long and productive career as a healer and shaman. The anthropologist Claude Levi-Strauss, in his paper 'The Sorcerer and his Magic', doesn't quite know what to make of it: 'but it is evident that he carries on his craft conscientiously, takes pride in his achievements, and warmly defends the technique of the b.l.o.o.d.y down against all rival schools. He seems to have completely lost sight of the fallaciousness of the technique which he had so disparaged at the beginning.'

Of course, it may not even be necessary to deceive your patient in order to maximise the placebo effect: a cla.s.sic study from 1965-albeit small and without a control group-gives a small hint of what might be possible here. They gave a pink placebo sugar pill three times a day to 'neurotic' patients, with good effect, and the explanation given to the patients was startlingly clear about what was going on: A script was prepared and carefully enacted as follows: 'Mr. Doe...we have a week between now and your next appointment, and we would like to do something to give you some relief from your symptoms. Many different kinds of tranquilizers and similar pills have been used for conditions such as yours, and many of them have helped. Many people with your kind of condition have also been helped by what are sometimes called 'sugar pills', and we feel that a so-called sugar pill may help you, too. Do you know what a sugar pill is? A sugar pill is a pill with no medicine in it at all. I think this pill will help you as it has helped so many others. Are you willing to try this pill?' A script was prepared and carefully enacted as follows: 'Mr. Doe...we have a week between now and your next appointment, and we would like to do something to give you some relief from your symptoms. Many different kinds of tranquilizers and similar pills have been used for conditions such as yours, and many of them have helped. Many people with your kind of condition have also been helped by what are sometimes called 'sugar pills', and we feel that a so-called sugar pill may help you, too. Do you know what a sugar pill is? A sugar pill is a pill with no medicine in it at all. I think this pill will help you as it has helped so many others. Are you willing to try this pill?' The patient was then given a supply of placebo in the form of pink capsules contained in a small bottle with a label showing the name of the Johns Hopkins Hospital. He was instructed to take the capsules quite regularly, one capsule three times a day at each meal time. The patient was then given a supply of placebo in the form of pink capsules contained in a small bottle with a label showing the name of the Johns Hopkins Hospital. He was instructed to take the capsules quite regularly, one capsule three times a day at each meal time.

The patients improved considerably. I could go on, but this all sounds a bit wishy-washy: we all know that pain has a strong psychological component. What about the more robust stuff: something more counterintuitive, something more...sciencey? Dr Stewart Wolf took the placebo effect to the limit. He took two women who were suffering with nausea and vomiting, one of them pregnant, and told them he had a treatment which would improve their symptoms. In fact he pa.s.sed a tube down into their stomachs (so that they wouldn't taste the revolting bitterness) and administered ipecac, a drug that which should actually induce induce nausea and vomiting. nausea and vomiting.

Not only did the patients' symptoms improve, but their gastric contractions-which ipecac should worsen-were reduced reduced. His results suggest-albeit it in a very small sample-that a drug could be made to have the opposite effect to what you would predict from the pharmacology, simply by manipulating people's expectations. In this case, the placebo effect outgunned even the pharmacological influences.

More than molecules?

So is there any research from the basic science of the laboratory bench to explain what's happening when we take a placebo? Well, here and there, yes, although they're not easy experiments to do. It's been shown, for example, that the effects of a real drug in the body can sometimes be induced by the placebo 'version', not only in humans, but also in animals. Most drugs for Parkinson's disease work by increasing dopamine release: patients receiving a placebo treatment for Parkinson's disease, for example, showed extra dopamine release in the brain.

Zubieta [2005] showed that subjects who are subjected to pain, and then given a placebo, release more endorphins than people who got nothing. (I feel duty bound to mention that I'm a bit dubious about this study, because the people on placebo also endured more painful stimuli, which is another reason why they might have had higher endorphins: consider this a small window into the wonderful world of interpreting uncertain data.) If we delve further into theoretical work from the animal kingdom, we find that animals' immune systems can be conditioned to respond to placebos, in exactly the same way that Pavlov's dog began to salivate in response to the sound of a bell.

Researchers have measured immune system changes in dogs using just flavoured sugar water, once that flavoured water has been a.s.sociated with immunosuppression, by administering it repeatedly alongside cyclophosphamide, a drug that suppresses the immune system.

A similar effect has been demonstrated in humans, when the researchers gave healthy subjects a distinctively flavoured drink at the same time as cyclosporin A (a drug which measurably reduces your immune function). Once the a.s.sociation was set up with sufficient repet.i.tion, they found that the flavoured drink on its own could induce modest immune suppression. Researchers have even managed to elicit an a.s.sociation between sherbet and natural killer cell activity.

What does this all mean for you and me?

People have tended to think, rather pejoratively, that if your pain responds to a placebo, that means it's 'all in the mind'. From survey data, even doctors and nurses buy into this canard. An article from the Lancet Lancet in 1954-another planet in terms of how doctors spoke about patients-states that 'for some unintelligent or inadequate patients, life is made easier by a bottle of medicine to comfort the ego'. in 1954-another planet in terms of how doctors spoke about patients-states that 'for some unintelligent or inadequate patients, life is made easier by a bottle of medicine to comfort the ego'.

This is wrong. It's no good trying to exempt yourself, and pretend that this is about other people, because we all respond to the placebo. Researchers have tried hard in experiments and surveys to characterise 'placebo responders', but the results overall come out like a horoscope that could apply to everybody: 'placebo responders' have been found to be more extroverted but more neurotic, more well-adjusted but more antagonistic, more socially skilled, more belligerent but more acquiescent, and so on. The placebo responder is everyman. You are a placebo responder. Your body plays tricks on your mind. You cannot be trusted.

How do we draw all this together? Moerman reframes the placebo effect as the 'meaning response': 'the psychological and physiological effects of meaning in the treatment of illness', and it's a compelling model. He has also performed one of the most impressive quant.i.tative a.n.a.lyses of the placebo effect, and how it changes with context, again on stomach ulcers. As we've said before, this is an excellent disease to study, because ulcers are prevalent and treatable, but most importantly because treatment success can be unambiguously recorded by having a look down there with a gastroscope.

Moerman examined 117 studies of ulcer drugs from between 1975 and 1994, and found, astonis.h.i.+ngly, that they interact in a way you would never have expected: culturally, rather than pharmacodynamically. Cimetidine was one of the first ulcer drugs on the market, and it is still in use today: in 1975, when it was new, it eradicated 80 per cent of ulcers, on average, in the various different trials. As time pa.s.sed, however, the success rate of cimetidine deteriorated to just 50 per cent. Most interestingly, this deterioration seems to have occurred particularly after the introduction of ranitidine, a competing and supposedly superior drug, onto the market live years later. So the self-same drug became less effective with time, as new drugs were brought in.

There are a lot of possible interpretations of this. It's possible, of course, that it was a function of changing research protocols. But a highly compelling possibility is that the older drugs became less effective after new ones were brought in because of deteriorating medical belief in them. Another study from 2002 looked at seventy-five trials of antidepressants over the previous twenty years, and found that the response to placebo has increased significantly in recent years (as has the response to medication), perhaps as our expectations of those drugs have increased.

Findings like these have important ramifications for our view of the placebo effect, and for all of medicine, since it may be a potent universal force: we must remember, specifically, that the placebo effect-or the 'meaning effect'-is culturally specific culturally specific.

Brand-name painkillers might be better than blank-box painkillers over here, but if you went and found someone with toothache in 6000 BC, or up the Amazon in 1880, or dropped in on Soviet Russia during the 1970s, where n.o.body had seen the TV advert with the attractive woman wincing from a pulsing red orb of pain in her forehead, who swallows the painkiller, and then the smooth, rea.s.suring blue suffuses her body...in a world without those cultural preconditions to set up the dominoes, you would expect aspirin to do the same job no matter what box it came out of.

This also has interesting implications for the transferability of alternative therapies. The novelist Jeanette Winterson, for example, has written in The Times The Times trying to raise money for a project to treat AIDS sufferers in Botswana-where a quarter of the population is HIV positive-with homeopathy. We must put aside the irony here of taking homeopathy to a country that has been engaged in a water war with neighbouring Namibia; and we must also let lie the tragedy of Botswana's devastation by AIDS, which is so phenomenal-I'll say it again: trying to raise money for a project to treat AIDS sufferers in Botswana-where a quarter of the population is HIV positive-with homeopathy. We must put aside the irony here of taking homeopathy to a country that has been engaged in a water war with neighbouring Namibia; and we must also let lie the tragedy of Botswana's devastation by AIDS, which is so phenomenal-I'll say it again: a quarter of the population are HIV positive a quarter of the population are HIV positive-that if it is not addressed rapidly and robustly the entire economically active portion of the population could simply cease to exist, leaving what would be effectively a non-country.

Leaving aside all this tragedy, what's interesting for our purposes is the idea that you could take your Western, individualistic, patient-empowering, anti-medical-establishment and very culturally specific placebo to a country with so little healthcare infrastructure, and expect it to work all the same. The greatest irony of all is that if homeopathy has any benefits at all for AIDS sufferers in Botswana, it may be through its implicit a.s.sociation with the white-coat Western medicine which so many African countries desperately need.

So if you go off now and chat to an alternative therapist about the contents of this chapter-which I very much hope you will-what will you hear? Will they smile, nod, and agree that their rituals have been carefully and elaborately constructed over many centuries of trial and error to elicit the best placebo response possible? That there are more fascinating mysteries in the true story of the relations.h.i.+p between body and mind than any fanciful notion of quantum energy patterns in a sugar pill? To me, this is yet another example of a fascinating paradox in the philosophy of alternative therapists: when they claim that their treatments are having a specific and measurable effect on the body, through specific technical mechanisms rather than ritual, they are championing a very oldfas.h.i.+oned and naive form of biological reductionism, where the mechanics of their interventions, rather than the relations.h.i.+p and the ceremony, have the positive effect on healing. Once again, it's not just that they have no evidence for their claims about how their treatments work: it's that their claims are mechanistic, intellectually disappointing, and simply less interesting than the reality.

An ethical placebo?

But more than anything, the placebo effect throws up fascinating ethical quandaries and conflicts around our feelings on pseudoscience. Let's take our most concrete example so far: are the sugar pills of homeopathy exploitative, if they work only as a placebo? A pragmatic clinician could only consider the value of a treatment by considering it in context.

Here is a clear example of the benefits of placebo. During the nineteenth-century cholera epidemic, deaths were occurring in the London Homeopathic Hospital at just one third of the rate as in the Middles.e.x Hospital, but a placebo effect is unlikely to be all that beneficial in this condition. The reason for homeo-pathy's success in this case is more interesting: at the time, n.o.body could treat cholera. So while hideous medical practices such as blood-letting were actively harmful, the homeopaths' treatments at least did nothing either way.

Today, similarly, there are often situations where people want treatment, but medicine has little to offer-lots of back pain, stress at work, medically unexplained fatigue and most common colds, to give just a few examples. Going through a theatre of medical treatment, and trying every medication in the book, will give you only side-effects. A sugar pill in these circ.u.mstances seems a very sensible option, as long as it can be administered cautiously, and ideally with a minimum of deceit.

But just as homeopathy has unexpected benefits, so it can have unexpected side-effects. Believing in things which have no evidence carries its own corrosive intellectual side-effects, just as prescribing a pill in itself carries risks: it medicalises problems, as we will see, it can reinforce destructive beliefs about illness, and it can promote the idea that a pill is an appropriate response to a social problem, or, a modest viral illness.

There are also more concrete harms, specific to the culture in which the placebo is given, rather than the sugar pill itself. For example, it's routine marketing practice for homeopaths to denigrate mainstream medicine. There's a simple commercial reason for this: survey data shows that a disappointing experience with mainstream medicine is almost the only factor that regularly correlates with choosing alternative therapies. This is not just talking medicine down: one study found that more than half of all the homeopaths approached advised patients against the MMR vaccine for their children, acting irresponsibly on what will quite probably come to be known as the media's MMR hoax. How did the alternative therapy world deal with this concerning finding, that so many among them were quietly undermining the vaccination schedule? Prince Charles's office tried to have the lead researcher into the matter sacked.

A BBC Newsnight Newsnight investigation found that almost all the homeopaths approached recommended ineffective homeopathic pills to protect against malaria, and advised against medical malaria prophylactics, while not even giving basic advice on mosquito-bite prevention. This may strike you as neither holistic nor 'complementary'. How did the self-proclaimed 'regulatory bodies' in homeopathy deal with this? None took any action against the homeopaths concerned. investigation found that almost all the homeopaths approached recommended ineffective homeopathic pills to protect against malaria, and advised against medical malaria prophylactics, while not even giving basic advice on mosquito-bite prevention. This may strike you as neither holistic nor 'complementary'. How did the self-proclaimed 'regulatory bodies' in homeopathy deal with this? None took any action against the homeopaths concerned.

And at the extreme, when they're not undermining public-health campaigns and leaving their patients exposed to fatal diseases, homeopaths who are not medically qualified can miss fatal diagnoses, or actively disregard them, telling their patients grandly to stop using their inhalers, and to throw away their heart pills. There are plenty of examples, but I have too much style to doc.u.ment them here. Suffice to say that while there may be a role for an ethical placebo, homeopaths, at least, have ably demonstrated that they have neither the maturity nor the professionalism to provide it. Fas.h.i.+onable doctors, meanwhile, stunned by the commercial appeal of sugar pills, sometimes wonder-rather unimaginatively-whether they should simply get in on the act and sell some themselves. A smarter idea by far, surely, is to exploit the research we have seen, but only to enhance treatments which really do do perform better than placebo, and improve healthcare without misleading our patients. perform better than placebo, and improve healthcare without misleading our patients.