Placebo Effect, Homeostasis, and Health Management

Recently I've been involved in research on the placebo effect, coming at it from a mixture of philosophical and evolutionary perspectives. The placebo effect is a very important aspect of all medicine. A large part of medical cures are effected by the patients themselves, when the medical procedure allows the patients to bring their own resources to bear to solve the problem. In the classical placebo case, you give a sugar pill and the patient uses this as an excuse to cure himself. But placebos are actually present in every kind of medical treatment. To the extent the patient believes the treatment is going to work, he allows himself to deploy his own healing resources in a way that he wouldn't have done otherwise.

How should we understand this? What questions should a science of the placebo effect be asking? Of course it's important to investigate the brain mechanisms that underlie these effects, and lots of researchers are already beginning to home in on the problem at the level of neurophysiology and immunology. But it's no less important to look at the bigger picture, and ask: Whatever is going on here, from a functional standpoint? If a placebo is releasing in people an ability to cure themselves, why don't they just get on with it? Why ever should anyone withhold self-cure? You'd think that when you're sick you should just get better if you can; you shouldn't need to wait for permission from a doctor, a shaman, or a psychotherapist to utilize your own resources.

It's this level of question that has set me looking for some possible evolutionary explanation. Why should humans and other animals hold healing resources in reserve? What can be the advantages of not getting better when you actually could? As I've looked further, I've found many examples of it.

People may die from cancer when they have immune resources still waiting in reserve which could have been deployed against the cancer. People die in head-on car collisions because they don't apply the brakes hard enough. When athletes are running a marathon, they may reach the end of what they can do and collapse from fatigue, when, in fact, their muscles still have significant reserves left in them.

What's going on?

You'll have guessed the way I want to go with this: my idea is that nature has designed us to play safe, and never to use up everything we've got — because we never know what might still lie around the corner. When we reach the end of a marathon there may still be a lion waiting at the finishing post that's going to suddenly give chase. When we're sick with an infection and respond with an immune reaction, we may still be hit by a further infection the next day. Remember the story of the wise and foolish virgins and their lamps: it's always wise to keep something in reserve.

I'm now thinking in terms of there being what I call a "natural health management system", which does a kind of economic analysis of what the opportunities and the costs of self-cure will be — what resources we've got, how dangerous the situation is right now, and what predictions we can make of what the future holds. It's like a good hospital manager who has to choose if and when to throw resources against this or that problem, to hold so much back, to decide if it's essential to build up this area or that area — basically to try to produce an optimal solution to the problem of maintaining health with enough left over to meet coming challenges.

If this is right, it makes the placebo effect fit into a much larger picture of homeostasis and health management. And it converges with ideas being developed by researchers coming from quite different disciplines. I've been particularly struck by the work of the South African physiologist, Timothy Noakes, who has come up with the idea of there being what he calls "a central governor" in the brain which regulates just how far the body should be allowed to go in meeting the demands of extreme exercise.

These ideas are big, because they are producing a new perspective on how we and other animals have evolved to manage our internal healing resources across the board. But it already goes much beyond mere theory.

There's a phenomenon, well known to sports physiologists and athletes called "interval training". If you want to improve your prowess as an athlete, one highly effective method of doing it is to build up in the following way. If you're a sprinter, for example, you sprint for two minutes and then relax and jog for five minutes. Then you repeat this pattern again, and again. The result is that you soon find you can run about 15% better than you could before.

Why does this work? According to Tim Noakes, what may be happening is this. In order to improve peak performance you need to persuade your central governor to let you go beyond your own self-imposed limits, when otherwise "cautionary tiredness" would kick in and say, "No more." And one way of doing this is by teaching your central governor that the risks are not actually so great after all. Through interval training you can teach your own brain that you are not going to get into trouble by pushing yourself a little further than you might otherwise have done.

Noakes' theory is a clever way of looking at how to stretch the limits of athletic performance. But what about applying the same idea in other areas? In particular, what about the possibility that we could have interval training for the immune system? If people are not deploying their immune resources to maximum extent, so that they don't get better when they could have, could we teach them by a similar schedule of exercise for the immune system that it's safe to do so?

Here's the experiment. Let's do it in mice before we try it in humans. We give a mouse a bacterial infection. The mouse gets sick, and throws its immune resources against the infection — but only so far as it dares. Twenty-four hours later we follow up with antibiotics, and the mouse gets better. So the mouse's health management system gets the message that it's safe to go at least this far. Now, a week later, we repeat this pattern of infection followed by relief. Then we do it again, and again. And what I'd hope we'd find is that the mouse's health management system will learn that it can afford to use more of its resources than it otherwise would have dared to, because every time it goes to its own self-imposed limits it discovers it's followed by safe recovery.

Now, suppose we take one mouse which has been put through this regime, and another mouse which hasn't, and we inject them both with a carcinogen. I predict that the mouse which has been through interval training for its immune system will survive the cancer in a way in which a mouse that hasn't done won't.

If this were to work with people, imagine how it might turn medicine around! It might prove to be one of the best ways ever of achieving one of the main goals of modern medicine, which is to get people to use their own healing resources to greater and better effect than they usually do.

I have to say I really like the idea. Maybe this interview will be remembered as its first airing (I hope!).

We're lucky Nick Humphrey did not solve the Consciousness Problem 40 years ago. We might have missed out on some of the wonderful details he's been exploring along the way. In my opinion, the Consciousness Problem (and a Theory of Everything for physics) is Nature's way of keeping us humble while drawing our attention to some of the details that really count. One of these is the placebo effect.

A few years ago I was in Phoenixville, Pennsylvania, a small town where many buildings were vacated when the steel industry declined. I was visiting the last company still manufacturing punched-card data processing machines, and they were doing a booming business (this was just before Y2K). But there was even more activity in the factory next door. Their product? Placebos. For almost any drug on the market, they produce an inert replica: round pink pills, triangular red ones, blue ovals, yellow tablets, the entire range. We know they work, but we do not understand why.

As I drove back into New Jersey on Highway 1, past one pharmaceutical giant after another, I pondered the irony that the drug companies have built research lab upon research lab in expensive Princeton, hoping to discover new products, while the placebos are made in an abandoned factory with no research labs (and no lawyers) because they have one product, no side effects, no patents — and it works. How it works is still a mystery. I look forward to Nick Humphrey shedding new light on this.

In Nick’s interesting theory of the placebo effect, he draws attention to the importance of a mechanism for keeping something in reserve, which the placebo effect partially overrides. When I worked in the field of tropical plant physiology, I came across an interesting parallel for this process. In annual plants, which die after fruiting, there is no need to keep anything in reserve. They give all they have got, continuing to form fruits until they run out of resources, with the result that the later-formed fruits get smaller and smaller. By contrast, in perennial plants, which need to keep something in reserve for the next year, the fruits formed early and late in the season are more or less the same size. Perennial plants yield less than their full capacity, because they hold back reserves for the following season. We are like perennials.

I have only space to show this for his work upon placebos and the "health management system".

At present, physiologists and neurophysiologists study the body and brain in terms of mechanical bottom up processes, not mechanical op down ones. Mental beliefs and expectations thus have no place in their models about the processes that lead to such things as pain, feeling unwell or the pleasure of an illegal drug. As a result, the fact that people's beliefs about medical inert pills prescribed by doctors effect their body and brain gets ignored. It just is not in the physiological scientific script much in the way that the fact that the coasts of Africa and South America snapped together like separated jig-saw puzzle pieces did not fit in with that of pre-plate tectonic geology. But yesterday's overlooked anomaly can turn into today's boring triviality. And while Nick's health management system theory is no plate tectonics (at least yet), his top down approach to placebos gives them a plausible place in science.

Nick's revolution is to put together facts with some commonsense.

First, much of what we call illness is not due to physiological dysfunction but the body's own self-healing. Temperature rises as part of a strategy to kill pathogens — pathogens if they had a choice would keep temperature stable. Likewise, we feel sick to conserve energy — pathogens do not in themselves make us feel groggy. "Sickness" therefore is not so much a physiological input as a physiological output.

Second, such top down self-healing is organized by goals that have been fined tuned by evolution to maximize our long term survival. The body, for example, needs to be run on the assumption that it can dip into reserves if the unexpected happens — hungry Panthera leo tend to turn up when they are least expected. And the body might not bother with self-healing if it can see it will get better by doing nothing. There is thus not one path to health but a variety of options. The health management system makes a top down choice upon them — and that introduces the possibility of such decisions being shaped by beliefs.

If you get infected with a rhinovirus, your body has choices. It could decide to go on an all out defence that ups body temperature, diverts energy resources into T cell attack, and ends up with fatigue and 'queasiness'. But it might also decide to tolerate the bug and gamble it will not cause major damage. That latter option is not as rare as might be expected 20% of two year old infants in one study (van Benten et al., 2003, Pediatric Allergy and Immunology, 14, 363) were found to have rhinovirus infection but none of the physiological responses, 'illness', that go with clearing respiratory viruses. The health management system can decide to fight or to leave alone. Thus if a person's health management system predicts the body will get rid of a virus without needing to fight it physiologically then they might decide to abort having a "cold". It does not take much for that to happen — swallowing a few tablets prescribed by a doctor is enough. It does not matter that in reality that they are inert sugar pills — if the health management system thinks it has had external help (even if it does not — as with a placebo), it can decide to turn off having a cold.