by Ben Goldacre
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 bloody 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 classic 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?’
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 passed 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 nausea and vomiting.
Not only did the patients’ symptoms improve, but their gastric contractions—which ipecac should worsen—were 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 associated 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 association was set up with sufficient repetition, they found that the flavoured drink on its own could induce modest immune suppression. Researchers have even managed to elicit an association 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 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 quantitative analyses 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, astonishingly, 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 passed, 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.
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 nobody had seen the T
V advert with the attractive woman wincing from a pulsing red orb of pain in her forehead, who swallows the painkiller, and then the smooth, reassuring 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 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—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 association 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 relationship 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 old–fashioned and naive form of biological reductionism, where the mechanics of their interventions, rather than the relationship 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 Middlesex 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, nobody 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 circumstances 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 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 document 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. Fashionable 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 perform better than placebo, and improve healthcare without misleading our patients.
6 The Nonsense du Jour
Now we need to raise our game. Food has become, without question, a national obsession. The Daily Mail in particular has become engaged in a bizarre ongoing ontological project, diligently sifting through all the inanimate objects of the universe in order to categorise them as a cause of—or cure for—cancer. At the core of this whole project are a small number of repeated canards, basic misunderstandings of evidence which recur with phenomenal frequency.
Although many of these crimes are also committed by journalists, we will be reviewing them later. For the moment we will focus on ‘nutritionists’, members of a newly invented profession who must create a commercial space to justify their own existence. In order to do this, they must mystify and overcomplicate diet, and foster your dependence upon them. Their profession is based on a set of very simple mistakes in how we interpret scientific literature: they extrapolate wildly from ‘laboratory bench data’ to make claims about humans; they extrapolate from ‘observational data’ to make ‘intervention claims’; they ‘cherry-pick’; and, lastly, they quote published scientific research evidence which seems, as far as one can tell, not to exist.
It’s worth going through these misrepresentations of evidence, mainly because they are fascinating illustrations of how people can get things wrong, but also because the aim of this book is that you should be future-proofed against new variants of bullshit. There are also two things we should be very clear on. Firstly, I’m picking out individua
l examples as props, but these are characteristic of the genre; I could have used many more. Nobody is being bullied, and none of them should be imagined to stand out from the nutritionist crowd, although I’m sure some of the people covered here won’t be able to understand how they’ve done anything wrong.
Secondly, I am not deriding simple, sensible, healthy eating advice. A straightforwardly healthy diet, along with many other aspects of lifestyle (many of which are probably more important, not that you’d know it from reading the papers) is very important. But the media nutritionists speak beyond the evidence: often it is about selling pills; sometimes it is about selling dietary fads, or new diagnoses, or fostering dependence; but it is always driven by their desire to create a market for themselves, in which they are the expert, whereas you are merely bamboozled and ignorant.
Prepare to switch roles.
The four key errors
Does the data exist?
This is perhaps the simplest canard of all, and it happens with surprising frequency, in some rather authoritative venues. Here is Michael van Straten on BBC Newsnight, talking ‘fact’. If you prefer not to take it on faith that his delivery is earnest, definitive, and perhaps even slightly patrician, you can watch the clip online.
‘When Michael van Straten started writing about the magical medicinal powers of fruit juices, he was considered a crank,’ Newsnight begins. ‘But now he finds he’s at the forefront of fashion.’ (In a world where journalists seem to struggle with science, we should note that Newsnight has ‘crank’ at one end of the axis, and ‘fashion’ at the other. But that chapter comes later.) Van Straten hands the reporter a glass of juice. ‘Two years added to your life expectancy in that!’ he chuckles—then a moment of seriousness: ‘Well, six months, being honest about it.’ A correction. ‘A recent study just published last week in America showed that eating pomegranates, pomegranate juice, can actually protect you against ageing, against wrinkles,’ he says.