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Authors: Ben Goldacre

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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 from 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, 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 flavored sugar water, once that flavored water has been associated with immunosuppression, by administering it repeatedly alongside cyclophos-phamide, a drug that suppresses the immune system.

A similar effect has been demonstrated in humans when the researchers gave healthy subjects a distinctively flavored drink at the same time as cyclosporine A (a drug that measurably reduces your immune function). Once the association was set up with sufficient repetition, they found that the flavored 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 characterize 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 analyzes 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 important 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 percent of ulcers, on average, in the various different trials. As time passed, however, the success rate of cimetidine deteriorated to just 50 percent. Most interestingly, this deterioration seems to have occurred particularly after the introduction of ranitidine, a competing and supposedly superior drug, onto the market five years later. So the selfsame 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 had increased significantly in recent years (as had the response to medication), perhaps as our expectations of those drugs increased.

Findings like these have important ramifications for our view of the placebo effect, and for all 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
B.C
., or up the Amazon in 1880, or dropped in on Soviet Russia during the 1970s, where nobody 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, 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 British novelist Jeanette Winterson, for example, has written in
The Times
(London) 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 neighboring 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 is 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 noncountry.

All this tragedy left aside, what’s interesting for our purposes is the idea that you could take your Western, individualistic, patient-empowering, antimedical establishment, and very culturally specific placebo to a country with so little health care 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 that so many African countries desperately need.

So, if you go off now and chat to an alternative therapist about the contents of this chapter—as I very much hope you will—what will you hear? Will he smile, nod, and agree that his 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, in which 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 in London, 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 homeopathy’s success in this case is more interesting: at the time, nobody could treat cholera. So while hideous medical practices such as bloodletting 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 theater 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 that have no evidence carries its own corrosive intellectual side effects, just as prescribing a pill in itself carries risks: it medicalizes problems, as we shall 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 in the U.K. 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 that really
do
perform better than placebo and improve health care without misleading our patients.

The Nonsense Du Jour
 

Now we need to raise our game. Food has become an international obsession. The newspapers sometimes seem to be engaged in a bizarre ongoing ontological project, diligently sifting through all the inanimate objects of the universe in order to categorize 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 that recur with phenomenal frequency. These intellectual crimes are ferried to you by journalists, celebrities, and, of course, “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 last, they quote published scientific research evidence that 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. First, I’m picking out individual 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.

Second, 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, and in reality, you can see this kind of thing on any station, with tedious frequency.

“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.” 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 aging, against wrinkles,” he says.

Hearing this, the viewer might naturally conclude that a study has recently been published in America showing that pomegranates can protect against aging. But if you go to Medline, the standard search tool for finding medical academic papers, no such study exists, or at least not that I can find. Perhaps there’s some kind of leaflet from the pomegranate industry doing the rounds. Van Straten goes on: “There’s a whole group of plastic surgeons in the States who’ve done a study giving some women pomegranates to eat, and juice to drink, after plastic surgery and before plastic surgery: and they heal in half the time, with half the complications, and no visible wrinkles!” Again, it’s a very specific claim—a human trial on pomegranates and surgery—and again, there is nothing in the studies database.

So could you fairly characterize this
Newsnight
performance as “lying”? Absolutely not. In defense of almost all nutritionists, I would argue that they lack the academic experience, the ill will, and perhaps even the intellectual horsepower necessary to be fairly derided as liars. The philosopher professor Harry Frankfurt of Princeton University discusses this issue at length in his classic 1986 essay “On Bullshit.” Under his model, “bullshit” is a form of falsehood distinct from lying: the liar knows and cares about the truth but deliberately sets out to mislead; the truth speaker knows the truth and is trying to give it to us; the bullshitter, meanwhile, does not care about the truth and is simply trying to impress us:

It is impossible for someone to lie unless he thinks he knows the truth. Producing bullshit requires no such conviction…When an honest man speaks, he says only what he believes to be true; and for the liar, it is correspondingly indispensable that he considers his statements to be false. For the bullshitter, however, all these bets are off: he is neither on the side of the true nor on the side of the false. His eye is not on the facts at all, as the eyes of the honest man and of the liar are, except insofar as they may be pertinent to his interest in getting away with what he says. He does not care whether the things he says describe reality correctly. He just picks them out, or makes them up, to suit his purpose.

 

I see van Straten, like many of the subjects in this book, very much in the “bullshitting” camp. Is it unfair for me to pick out this one man? Perhaps. In biology fieldwork, you throw a wired square called a quadrat at random out onto the ground, and then examine whatever species fall underneath it. This is the approach I have taken with nutritionists, and until I have a Department of Pseudoscience Studies with an army of Ph.D. students doing quantitative work on who is the worst, we shall never know. Van Straten seems like a nice, friendly guy. But we have to start somewhere.

Observation or Intervention?

 

Does the rooster’s crow cause the sun to rise? No. Does this light switch make the room get brighter? Yes. Things can happen at roughly the same time, but that is weak, circumstantial evidence for causation. Yet it’s exactly this kind of evidence that is used by media nutritionists as confident proof of their claims in our second major canard.

Here is an interesting example from Angela Dowden, who, according to
The Daily Mirror
, is “Britain’s leading nutritionist.” In one of her columns in the
Mirror
explaining which foods offer protection from the sun during a heat wave, she writes: “An Australian study in 2001 found that olive oil (in combination with fruit, vegetables and pulses) offered measurable protection against skin wrinkling. Eat more olive oil by using it in salad dressings or dip bread in it rather than using butter.”

That’s very specific advice, with a very specific claim, quoting a very specific reference, and with a very authoritative tone. It’s typical of what you get in the papers from media nutritionists. Let’s go to the library and fetch out the paper she refers to (“Skin wrinkling: can food make a difference?” Purba, M. B., et al.
Journal of American College of Nutrition
20, no. 1 [February, 2001]: 71–80). Before we go any further, we should be clear that we are criticizing Dowden’s
interpretation
of this research, not the research itself, which we assume is a faithful description of the investigative work that was done.

This was an observational study, not an intervention study. It did not give people olive oil for a time and then measure differences in wrinkles. Quite the opposite, in fact. It pooled four different groups of people to get a range of diverse lifestyles, including Greeks, Anglo-Celtic Australians, and Swedish people, and it found that people who had completely different eating habits—and completely different lives, we might reasonably assume—also had different amounts of wrinkles.

To me this is not a great surprise, and it illustrates a very simple issue in epidemiological research called “confounding variables”: these are things that are related both to the outcome you’re measuring (wrinkles) and to the exposure you are measuring (food), but that you haven’t thought of yet. They can confuse an apparently causal relationship, and you have to think of ways to exclude or minimize confounding variables to get to the right answer, or at least be very wary that they are there. In the case of this study, there are almost too many confounding variables to describe.

I eat well—with lots of olive oil, as it happens—and I don’t have many wrinkles. I also have a middle-class background, plenty of money, an indoor job, and, if we discount infantile threats of litigation and violence from people who cannot tolerate any discussion of their ideas, a life largely free from strife. People with completely different lives will always have different diets, and different wrinkles. They will have different employment histories, different amounts of stress, different amounts of sun exposure, different levels of affluence, different levels of social support, different patterns of cosmetics use, and much more. I can imagine plenty of reasons why you might find that people who eat olive oil have fewer wrinkles, and the olive oil’s having a causative role, an actual physical effect on your skin when you eat it, is fairly low down on my list.

Now, to be fair to nutritionists, they are not alone in failing to understand the importance of confounding variables, in their eagerness for a clear story. Every time you read in a newspaper that “moderate alcohol intake” is associated with some improved health outcome—less heart disease, less obesity, anything—to gales of delight from the alcohol industry, and, of course, from your friends, who say, “Ooh, well, you see, it’s better for me to drink a little…” as they drink a lot—you are almost certainly witnessing a journalist of limited intellect, overinterpreting a study with huge confounding variables.

This is because—let’s be honest here—teetotalers are not like everyone else. They will almost certainly have a reason for not drinking, and it might be moral, or cultural, or perhaps even medical, but there’s a serious risk that whatever is causing them to be teetotal might also have other effects on their health, confusing the relationship between their drinking habits and their health outcomes. Like what? Well, perhaps people from specific ethnic groups who are teetotal are also more likely to be obese, so they are less healthy. Perhaps people who deny themselves the indulgence of alcohol are more likely to indulge in chocolate and chips. Perhaps preexisting ill health will force you to give up alcohol, and that’s skewing the figures, making teetotalers look unhealthier than moderate drinkers. Perhaps these teetotalers are recovering alcoholics: among the people I know, they’re the ones who are most likely to be absolute teetotalers, and they’re also more likely to be fat, from all those years of heavy alcohol abuse. Perhaps some of the people who say they are teetotal are just lying.

This is why we are cautious about interpreting observational data, and to me Dowden has extrapolated too far from the data in her eagerness to dispense—with great authority and certainty—
very
specific dietary wisdom in her newspaper column (but of course, you may disagree, and you now have the tools to do so meaningfully).

If we were modern about this, and wanted to offer constructive criticism, what might she have written instead? I think, both here and elsewhere, that despite what journalists and self-appointed “experts” might say, people are perfectly capable of understanding the evidence for a claim, and anyone who withholds, overstates, or obscures that evidence, while implying that she’s doing the reader a favor, is probably up to no good. MMR is an excellent parallel example of where the bluster, the panic, the “concerned experts,” and the conspiracy theories of the media were very compelling, but the science itself was rarely explained.

So, leading by example, if I were a media nutritionist, I might say, if pushed, after giving all the other sensible sun advice, “A survey found that people who eat more olive oil have fewer wrinkles,” and I might feel obliged to add, “Although people with different diets may differ in lots of other ways.” But then, I’d also be writing about food, so: “Never mind, here’s a delicious recipe for salad dressing anyway.” Nobody’s going to employ me to write a nutritionist column.

From the Lab Bench to the Glossies

 

Nutritionists love to quote basic laboratory science research because it makes them look as if they are actively engaged in a process of complicated, impenetrable, highly technical academic work. But you have to be very cautious about how you extrapolate from what happens to some cells in a dish on a laboratory bench to the complex system of a living human being, where things can work in completely the opposite way from what laboratory work would suggest. Anything can kill cells in a test tube. Fairy liquid will kill cells in a test tube, but you don’t take it to cure cancer. This is just another example of how nutritionism, despite the alternative medicine rhetoric and phrases like “holistic,” is actually a crude, unsophisticated, old-fashioned, and, above all,
reductionist
tradition.

Here is another example from Michael van Straten—who has fallen sadly into our quadrat, and I don’t want to introduce too many new characters or confuse you—writing in the British
Daily Express
as its nutrition specialist: “Recent research,” he says, has shown that turmeric is “highly protective against many forms of cancer, especially of the prostate.” It’s an interesting idea, worth pursuing, and there have been some speculative lab studies of cells, usually from rats, growing or not growing under microscopes, with turmeric extract tipped on them. There is some limited animal model data, but it is not fair to say that turmeric, or curry, in the real world, in real people, is “highly protective against many forms of cancer, especially of the prostate,” least of all because it’s not very well absorbed, since your liver tends to absorb and metabolize it before it can reach other organs.

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