Monday, February 19, 2001

The Placebo Effect


Take two aspirin and call me in the morning.

How long have we heard this medical advice?  And, more importantly, how long has it been accepted as standard medical practice?

Perhaps, Hippocrates was the first doctor to not only prescribe willow bark, the naturally-occurring analgesic that we call aspirin, but also prescribe the advice of the placebo-dealing shaman whom he intended to replace.

For well over the twenty-some centuries since Hippocrates began codifying medical treatment, we have known that plants and herbs possess properties that treat symptoms or conditions.  And we know as well that the mere suggestion by someone we hold in esteem also works in treating ailments.  What we still don’t know is exactly how combining the two procedures really works in the mind and the body.  Whether our physician wears a white coat or grass skirt is immaterial.  Whether the pill is a placebo or the real McCoy can be immaterial.  The placebo effect is alive and well, still confounding modern science.

Humankind first learned of natural medicines by observing the foraging creatures that shared our habitat.  As an example, we know that the bark of the Slippery Elm root is an aid to digestive disorders.  How did we come to know this?  Probably by observing a deer, or another creature, eat the very same bark during a hard winter when normal forage was low or non-existent.

But we didn’t stop there.  We experimented.  For example, Princess Chinchon of Spain, on a visit to the New World, was cured of malaria because the Jesuit priests traveling with her had learned from the native Indians that the bark of a certain tree contained the medicine that fought the fever.  Today, we call this tree Cinchona, resultant from her name and the historical incident.  But how much of a role did the Jesuits, the priests she trusted with her life, play in her cure?  And then we must also ask, who was it in the tribe that convinced the priests to try the cure?

We have tried to differentiate between placebos and medicines for quite a long time.  The modern double-blind drug test has provided us with the best evidence yet that the placebo effect complicates our ability to truly calculate the scientific efficacy of a particular medicine.  In essence, we are still mired in the 1600’s, trying to solve the same dilemma that faced Princess Chinchon’s priest.

That is: Is the bark worse than the bite?

Modern Test Results

Modern double-blind tests tell us that Drug A has an efficacy of X% and that the placebo used as a control in the test exhibits an efficacy of X/2%, or X/3%, or some other factor.  The drug being tested is approved for use and achieves marketability only when its efficacy is significantly higher than the placebo.  For some reason, however, the placebo has success in such trials and these results are assumed to occur because the patient receiving the placebo actually believes that he/she is really taking a drug with positive medicinal effects.

In 1992, a national study of 10,000 terminally-ill cancer patients reported that, over ten years, some patients were still alive.  After being told that they were terminally ill, the patients in the study were allowed to choose their preferred method of treatment.  While most chose chemotherapies or radiation, a significant minority opted for non-traditional remedies which included such off-the-wall cures as daily coffee enemas.

When broken into these three categories (chemo, radiation, other), the results were striking.  During each year of the study, as one would expect, a percentage of patients died.  But the relative population that survived in each year was about the same.  Although most died, in year ten, about 3-8% were still alive.  Was this minority misdiagnosed?  Was their survival due to medical treatment?  Or was their survival due to the placebo effect?

No matter how we test the patient population, we always seem to come back to the obvious-that the mind is at work in aiding the drug, the treatment, or the placebo.

Are We Looking in the Right Place?

Let’s stop looking at results for a moment and ask how the patient became ill in the first place.

Princess Chinchon contracted malaria because she was bitten by a mosquito. Right?

Long before Spain laid claim to the New World, malaria, mosquitoes, Cinchona trees, and people all coexisted in the Tropics.  Through a long process of trial and error, the tribal shamans finally discovered that the tree bark cured the malarial fever.

Before the cure was discovered, malaria did not wipe out the tribe as we might expect. Indeed, there had to be some number of Indians who were most likely impervious to the infection.  For those who did succumb, some died while others recuperated.  What we can say with certainty is that each mosquito bite did not result in a case of malaria.

It is odd that some Indians might never contract malaria while others were almost guaranteed to die from it.  Could the reason be genetic?  Could it be from a natural antibody or a congenitally-passed antibody?  Or is it a result of something else?  For instance: Did breathing the smoke from a campfire made from Cinchona wood impart a degree of protection?

To digress on Cinchona, it is interesting that malaria and the curative tree bark are found in the same swamp.  This fact seems to transcend mere biological coincidence.  An astute investigator would examine any cause-effect relationship between the two.  For in this case, the tree might be the root of the disease as well as the source of its cure.

Closer to home, the American Chestnut tree, until it became extinct, was widely regarded to have some causal effect for respiratory ailments in the Appalachian population.  Chestnut was the predominant hardwood species in the forest.  According to the ‘old-timers’, this wheezing and coughing seems to have disappeared completely when the blight killed the Chestnuts some eighty years ago.

Science has always investigated cause-effect relationships.  It is, after all, sensible to do this.  For this reason, we discovered that mosquitoes are the vector for malaria.  But we have too often assumed that the cause-effect scenario is always at work and that we will somehow discover the "magic bullet" if given enough experimenting.

In the case of malaria, our magic bullet approach to solving problems led to the wholesale destruction of swamps, the breeding grounds for mosquitoes, and the mass spraying of DDT.  The result?  Malaria and mosquitoes waned but still survived.  The Law of Unintended Consequences proved, once again, that its staying power was absolute.

If we are to continue this pattern of solving medical problems, we would be wise to truly determine the cause and effect relationship before trying to dismantle what we think it is.  In truth, the human race is probably too ignorant to ever determine the cause of anything.  Unless, that is, we call it an accomplishment to say that we learned that we imported the blight that killed the Chestnut or that we developed an insecticide that almost caused the extinction of several avian species.

We are always tempted to assume that a cause-effect relationship with foreign bodies exists.  Why?  Because we have proved it in so many cases.  But are we not fooling ourselves by eliminating ourselves as the cause, or at least the abettor, in certain situations?  At the same time that Princess Chinchon was being cured by illiterate shamans wearing loin cloths, the esteemed philosopher, Rene Descartes, was writing "Cogito, ergo sum." (I think, therefore I am) for the Holy See in Rome.  What would Descartes say about the placebo effect if he were alive today?  Indeed, what would he say about how we contract a malady?

Stress-The Un-Placebo?

When thinking of possible reasons for infections, stress is generally on the list of usual suspects.  Our dear Princess was obviously under stress when she arrived in South America.  Her diet had changed dramatically as had her source of drinking water.  She probably slept little on the voyage which spanned five time zones, lasted 6-8 weeks, and took her from the temperate zone to the humid tropics.  Add to that, a fear-inspiring sojourn into the rain forest jungle, and you have a highly-stressed specimen.

Stress, in simplest terms, means that a weakened support causes a neighboring support to bear a heavier load.  A diet devoid of just one vitamin causes beriberi, rickets, or scurvy.  A diet devoid of iodine causes goiter.  A diet diminished in several vitamins or elements, in total or in combination, just might lead to __________ (take your pick).

The great epidemics in history all followed times of great stress.  The most famous, the bubonic plague in Europe, came in three waves, each after a period of famine caused mainly by war.  More recently, the Spanish flu swept the globe at the close of World War I.  These epidemics are all the more remarkable because they ceased after stress was reduced or eliminated.

Even if Princess Chinchon had eaten a perfectly healthy diet and drank only Perrier water, that is not to say she would not have been under stress at some point.  Some people cannot process what they eat in the proportions necessary to fend off problems.  While person A might receive 150% of the vitamin C requirement from one orange, person B might need to eat three oranges or take supplements to achieve the daily need.  In this regard, stress is defined by the individual’s body, not the public trauma.

Stress, therefore, is a contributory factor to nearly everything that befalls us. But how do we measure its impact?

Expectancy Theory

Expectancy Theory is "Pavlov’s Humans for Dogs."  In other words, the dog knows that if it jumps through hoops, the human will give it a treat.  Though you’d never convince Pavlov of this, it is also the reason why cows look at people with that incredulous bovine stare.  And it is the reason why doctors carry little white note pads in their coat pocket.  A sick-acting patient needs a reward, just like Pavlov’s dog, because the Rx is the first step to getting better.  You don’t even have to take the pill for the placebo effect to kick in.

Let’s give Pavlov’s dog some credit.  With its superior olfactory senses, the dog probably smelled the biscuit coming down the hallway in Pavlov’s briefcase.  As for the typical human patient, he/she knows about the prescription pad long before arriving at the clinic.

In simplest terms, you go to the doctor and you expect to be cured, or in the least, comforted.  Take two aspirin, ….

Where Next?

Aspirin works in the body in ways that are still not understood.  Medically, that is.  Aspirin just might be an almost perfect drug to study the placebo effect.  Why?  Because it apparently triggers responses in the brain that signal the body that it is getting better.  Obviously, the analgesic effect of aspirin has much to do with this because the body feels an immediate relief from pain.  But is this not the very reward that Pavlov’s dog jumps through hoops for?

In the movie The Birdcage, the character Starina complains that he has no more Pirin tablets and cannot go on stage.  We then learn that Pirin are aspirin with the ‘a’ and ‘s’ scraped off.  Yes, it is a grand joke.  But intuitively, we know that it’s true.

Certainly, the body can distinguish a placebo from a drug.  The mind can only mask some of the reactions that the drug causes and the mind can only initiate some of the responses that the placebo is supposed to cause.

Aspirin, by being both a placebo-effect inducer and a medicine, shows us that we have been wrong to conduct double blind drug tests by offering the test subject either the drug or the placebo.  Like a cow, I stare incredulously at Science, wondering why these tests don’t offer both the drug and the placebo to the patient as a third alternative in the study.  Are we afraid to learn of the true compounding power of the placebo effect?

To understand why aspirin is so successful at triggering brain responses which in turn trigger the placebo effect is to understand the placebo effect itself.  It is precisely the response of the mind that allows the body to heal.  It is this response that makes the body receptive to the medicine.  Hence, it’s efficacy.  In understanding aspirin, I think we can solve the dilemma that has escaped us for so long.

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Long before Athens was Athens and the New World was new to the Old, tribal shamans prescribed one kind of tree bark for pain and another for fever.  The Ancients knew their laboratory well so we must ask: Have we overlooked something simple in our quest to develop synthetic drugs and medicines?

Who knows?  Maybe it was the aroma of the Cinchona bark or the bitter taste of its tea that made it work wonders for the Princess.  Then again, maybe her priest had read Descartes treatise.