Can we think ourselves well?

'Cure' by Jo Marchant is longlisted for the 2017 Wellcome Book Prize, which celebrates the best books engaged with medicine and health. Here, Jo introduces an extract from the book.

Can we think ourselves well? It’s a controversial question. Alternative therapists commonly claim that positive thinking can cure serious conditions from broken spines to cancer, while sceptics counter that any idea of healing thoughts is deluded and dangerous. With such deeply entrenched positions, it’s hard to work out whom to believe.

In Cure, I set out to investigate what the science really says about whether our minds influence our bodies. I wanted to know what the mind can do and what it can’t, how it works, and how can we take advantage of these effects in our own lives.

Although scientists are often skeptical about mind-body links, there is mounting evidence that our thoughts, emotions and beliefs are accompanied by physical changes in our bodies and brains. The effects can be particularly dramatic when it comes to symptoms such as pain, nausea and fatigue. We tend to imagine that the way we feel directly reflects the physical state of our bodies, but researchers are finding that this isn’t true. Instead, our assessment of a threat, conscious or unconscious, triggers the release of chemicals in the brain that push relevant symptoms up and down.

This is why worrying about a symptom can make it worse, or why taking a placebo (a medical treatment with no active ingredient) can make us better. Many conventional treatments – painkillers such as morphine, for example – work by mimicking these natural chemicals. But we can harness thoughts and beliefs to influence the same pathways, and researchers are starting to develop new kinds of therapies, from honest placebos to virtual reality, to do just that.

The powers of the mind aren’t limited to symptoms, however. Many aspects of our physiology, from heart rate and digestion to the immune system, are ultimately controlled by the brain, via the autonomic nervous system. You can’t generally will changes directly, but these processes are still highly sensitive to psychological cues. Thinking of a lemon makes you salivate; seeing an erotic picture turns you on; feeling afraid or stressed boosts your heart rate, dilates your pupils and triggers a branch of the immune system known as inflammation.

These links help to prepare our bodies for changes in the environment. But they can also be crucially important in the development and progression of disease. Finding ways to reduce stress is a huge focus for research – from visualization techniques that cut the complication rate during surgery, to the finding that people with strong social bonds live longer. There are other approaches too, though. One mind-body effect I found particularly surprising was that we can train our immune systems to respond to taste and smell. Researchers hope this will help to reduce drug doses (and therefore side effects) in allergies, autoimmune conditions, organ transplants and even some forms of cancer.

People often think of the mind’s influence on the body as somehow magical or mysterious. I would argue that it’s just biology. Through neurotransmitters and nerves, our mental state affects both the symptoms we experience and the underlying physiology of disease.

That means it’s wrong to see the mind a miracle cure: there are clear limits to what it can do. But the sceptics are also wrong to dismiss it. The science is now incontrovertible that our minds have real, measurable effects on our health. Surely embracing that is a more scientific and evidence-based approach than relying ever more heavily on physical interventions and drugs.

- Jo Marchant is an award-winning science journalist and author. The following extract from Cure is reproduced with kind permission from Canongate Books. Read more about the Wellcome Book Prize, and find comment on last year's competition in our archive.

PAVLOV’S POWER

How to Train your Immune System

Karl-Heinz Wilbers pops open a small plastic case and takes out four foil blister packs of drugs. Myfortic, tacrolimus… these are the names he reads every day, and on which his life now depends. Today there’s an extra pill, a chunky white capsule that smells slightly of fish. Before he takes it, he switches on the CD player and cues up ‘Help Me’, by Johnny Cash. And he pours himself a glass of a bright green liquid that smells strongly of lavender.

Karl-Heinz is a retired psychiatrist from Essen in northern Germany. He’s an earnest, academic man with a quiet, almost melancholy demeanour and small, wire-rimmed glasses. Sixteen years ago, his kidneys failed. It’s not clear why, he says, although the most common causes are diabetes and high blood pressure. He became one of 80,000 Germans who depend on dialysis, a procedure in which a patient’s blood is regularly fed through a tube into a machine and filtered to remove waste products before being passed back into their body.

He was hooked up to the machine for nine hours at a time, four-to-five times a week. Karl-Heinz was lucky, he was able to have the dialysis overnight at home. ‘But you can’t sleep the whole night,’ he says. ‘Alarms go off. You have to check the machine, change fluids. You have two big needles in your arm.’ He shows me a large scar on the inside of his forearm, where the needles sat in his flesh night after night.

He was alive. He could still walk his dog and was able to paint. But his dependence on the dialysis machine made it impossible to travel, and his chances of surviving to enjoy retirement with his wife and daughter weren’t good. The average life expectancy for patients on dialysis is just five years.

After 12 years on dialysis, Karl-Heinz was beating the odds. So when he was finally given the chance of a kidney transplant he said ‘Yes’, albeit with some trepidation. ‘After that, my life was very different,’ he says. ‘The freedom you get. Being mobile.’ He tells me that in the four years since the transplant, he and his wife have visited their daughter in the UK’s Lake District, some­thing that would have been impossible on dialysis. They have flown to New York twice, and are planning a trip to the south of England.

But he paid a heavy price. He is no longer tied to the dialysis machine, but to stop his body from rejecting the foreign organ he has to take powerful drugs that suppress his immune system every day for the rest of his life. They put him at risk of life-threatening infections, and he lives with the constant threat of cancer.1 There are neurological side effects; he gets a painful, burning sensation in his feet. And the toxicity of the drugs puts pressure on his precious kidney. Get the dose too low, and his body could reject it. Too high, and the toxicity could cause the organ to fail.

‘Help Me’ is one of Karl-Heinz’s favourite songs; he has chosen it because it puts him in a calm, thoughtful frame of mind. As he listens to the lyrics, he swallows the chunky capsule and downs his lavender drink. He knows that unlike the rest of the pills in his plastic case, these contain no active drug. He’s taking them as part of a pioneering trial to investigate whether this ritual – the drink, the pill, the music – has the power to shape his body’s response to his transplant, in this case suppressing it above and beyond the effects of his drugs alone.

The placebos we’ve looked at so far are based on conscious belief or expectation. You think a pill or injection will have a certain effect, and then it does. Although such fake treatments can create biological changes in the body, they mostly influence subjective symptoms such as pain – affecting how we feel, not our underlying disease. But Karl-Heinz is hoping that his mind will trigger another type of mechanism that can influence basic biological functions, including the immune system.

Proponents say this phenomenon has the potential to slash drug doses for transplant patients like Karl-Heinz, as well as those suffering from allergies, autoimmune disorders and even cancer. But it’s far from mainstream medicine, and most immunologists barely acknowledge that it even exists.

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Imagine taking a plump, yellow lemon from your fruit bowl. Its skin is smooth to touch, glossy and dotted with pores. Now put the lemon on a plate and cut it into quarters. Juice drips down the knife blade onto your fingers and the smell hits you: sharp and sour. You pick up one of the segments and notice how its flesh glistens, the light shining off hundreds of tiny liquid compart­ments each full to bursting. Then you bite into it, sucking the rush of acid juice onto your tongue.

Did your mouth pucker as you read that paragraph? Did your salivary glands tingle into action, preparing your tongue for the imminent attack of acid? If so, you must have eaten a lemon before, and you have learned the appropriate physiological response. But here’s the crucial point. You no longer have to physically eat a lemon to experience these changes. Your body triggers them automatically in response to the sight, the smell – or just the thought – of a lemon, well before you actually taste the juice.

This form of learning, in which a mental cue drives a physical response, is called conditioning. It was famously discovered by a Russian physiologist called Ivan Pavlov in the 1890s. Pavlov was studying how dogs started salivating when he brought them food. Then he noticed that they started to salivate as soon as he entered the room, whether he was carrying food or not. The dogs had learned to associate his presence with being fed. After a while, they responded to him just as they did to their meat.

Pavlov showed that he could train the dogs to associate any stimulus – an electric shock, say, or a light or bell – with dinner. Once the association was learned, that signal on its own was enough to make the dogs drool. It’s a beautiful example of how the body doesn’t just react blindly to physical events and changes – lemon juice hitting our tongue, for example. It uses psycho­logical cues to stay one step ahead.

Such anticipatory responses prepare us for important biological events such as eating or sex. Your tummy rumbles when you perceive signs – the clock, perhaps, or news headlines on the radio – that tell you it’s time for lunch. You get excited by the smell of a lover’s perfume, or the sound of their voice. (Psychologists have conditioned volunteers to become sexually aroused by neutral images from guns to penny jars, simply by pairing them with erotic film clips.) The memory of a song your mother used to sing to you at bedtime slows your heart rate and calms you down.

Other conditioned responses have evolved to protect us, preparing us to flee danger, or encouraging us to avoid it. If someone is bitten by a dog in childhood, the sight of a dog later in life may be enough to send their heart racing in fear (this is the basis of many phobias). If we eat a food that gives us a stomach upset, the mere thought or smell of that food may be enough to make us feel sick again. In some cases, even a particular place that we associate with sickness can trigger symptoms. This is why many people having chemotherapy get sick as soon as they arrive at the hospital, before their treatment session even starts.

This much is fairly well known. Pavlov’s work on those salivating dogs is world famous. What’s less familiar to most scientists, let alone the rest of us, is that conditioning can also trigger placebo responses. If we swallow a pill that contains an active drug, we learn to associate that pill with a particular physiological change. Later, if we receive a look-a-like placebo, we can experience the same change. It’s an automatic response in the body that happens regardless of whether we know the pill is fake. But it is triggered via conscious psychological cues – such effects don’t occur if we’re given a placebo while sedated, for example, or without knowing that we’ve taken it.

Placebo responses based on physiological conditioning often occur in addition to responses based on conscious expectation. For example, Benedetti tells me that across his trials, the percentage of volunteers who respond to a placebo painkiller is extremely variable, anything from 0% to 100% depending on the circum­stances. But if he first gives them a series of identical-looking injections containing an active drug, the proportion who subse­quently respond to the placebo soars to a reliable 95–100%. ‘You can bet that virtually all patients will respond,’ he says – even if they know that the final injection isn’t real.2

Could such responses be useful in medicine? We heard in Chapter 1 how North Carolina paediatrician Adrian Sandler tested the hormone secretin as a treatment for autism, and found that it was no more effective than placebo. Yet he was struck by how dramatically the children in both groups improved, and he was unable to leave that revelation behind. Any drug that helped as much as the placebo had in his study would be leapt on as a potent treatment. Yet because this remedy involved the mind rather than a pharmaceutical, it was being ignored. In his spare time, Sandler started reading up on placebos, and wondered how he might be able to use them – without deceiving his patients.

The most prevalent diagnosis among the children he saw every day was attention deficit hyperactivity disorder (ADHD). As the name suggests, these kids were inattentive, hyperactive, impulsive. They were constantly talking and fidgeting, they were unable to wait their turn, and they found it impossible to focus in school. Medication helped them to control their symptoms but still caused problems, from irritable outbursts when the drug wore off in the evening to weight loss and stunted growth. ‘It becomes a balancing act in the clinic,’ he says, ‘trying to find [a dose] that is giving sufficient benefit without giving excessive side effects.’3

Sandler wondered whether a placebo might help these children to manage their symptoms on a lower dose of drug. He decided to give his placebos honestly, as part of a regime that would hope­fully harness the power of both expectation and conditioning. Seventy ADHD patients, aged six to twelve, completed his two-month trial.

These children were split randomly into three groups. One group underwent a conditioning regime. For one month they received their normal medication, but also swallowed a distinctive green-and-white capsule alongside their drug – they knew this was inert, but Sandler hoped that they would learn to associate it with the physiological response to their active medication. For the second month they received half their usual drug dose, as well as the placebo capsule.

Sandler compared these patients against two control groups, neither of which received any conditioning. One group received their full dose of medication for the first month and a half dose for the second month – just like the conditioning group. The last group got a full dose all the way through.

Sandler published his results in 2010. As expected, in the half-dose control group, the children’s symptoms got significantly worse in the second month of the trial. But the conditioned group remained stable, doing just as well as the full-dose patients. In fact there were hints that kids in this group did even better, suffering fewer side effects than those on the full dose of drug.4

It is the first and only trial in which honest placebos have been given to children. Sandler says that parents and kids alike embraced the idea, and that more than half of them wanted to keep taking the placebo once the study was over. ‘It is the best medicine I’ve had,’ one child told him afterwards. ‘I think it tricked the brain into thinking it would work.’ Sandler’s study is small and prelim­inary, but combined with Benedetti’s findings, it hints that doctors could use simple conditioning procedures to boost the effectiveness of placebos, without any deception required.

For me, that’s an exciting finding. By using expectation and conditioning together, ethical placebos could potentially help to reduce drug doses for millions of patients around the world, in conditions from pain and depression to Parkinson’s and ADHD.

There’s something else about conditioned responses, however, that opens up an entirely new landscape of possibility. These learned, unconscious associations aren’t limited to the subjective symptoms – like the distractibility of those with ADHD – that are shaped by conventional placebo effects. They can also influ­ence the immune system, providing a route by which the mind can become a weapon in the body’s fight against disease. The mind, in other words, can do much more than help us to feel and perform better. Through conditioning, it might make the difference between life and death.

Jo Marchant will be appearing at Book Slam x Wellcome Book Prize at Wellcome Collection on 13 March.

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  1. Someone with a transplanted kidney is two to three times more likely to develop cancer compared to a person of the same age and sex in the general population, mainly because the drugs that prevent their body from rejecting the organ also suppress immune responses that would normally protect them from cancer. Wong, G. et al. Kidney International 2014; 85: 1262–1264
  2.  Interview with Fabrizio Benedetti, Breuil-Cervina, 21 March 2014, and email interview 13 February 2014.
  3. Telephone interview with Adrian Sandler, 7 February 2014.
  4. Sandler, A.D. et al. Journal of Developmental & Behavioral Pediatrics 2010; 31: 369–375

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