Read 13 Things That Don't Make Sense Online
Authors: Michael Brooks
IN
the illusion of free will, it seems we have been equipped with a neurological sleight of hand that, while contrarational,
helps us deal with a complex social and physical environment. This is not the only mind trick that evolution has bestowed
upon us. There is another neurological anomaly that sits beyond our conscious control, and it is certainly too late to leave
this one alone; it has already been scientifically deconstructed and set as a central pillar of our health-care system, arbitrating
what works and what doesn’t in modern medicine. It is the placebo effect.
"I
t has brought me great comfort to know that I could, in some way, help people feel better,” said Leo Sternbach, inventor of
the antianxiety drug diazepam. Sternbach certainly did that—in spades. What is only just starting to emerge is just how much
Leo Sternbach’s drug depends on people helping themselves to feel better.
From 1969 to 1982, diazepam, marketed as Valium, was the top-selling pharmaceutical in the United States. At the height of
its powers, Sternbach’s employer, the pharmaceutical giant Hoffman LaRoche, sold 2.3 billion of the little yellow pills marked
with a
V
. That was in 1978, and the drug had already been part of popular culture for more than a decade; “Mother’s Little Helper”
by the Rolling Stones, released in 1966, is a satire on domestic abuse of Valium. In the same year that song was released,
the drug gained a starring role in the cult novel
Valley of the Dolls
; diazepam “dolls” were the lead characters’ means of getting through the strains of life in New York. Diazepam is now, according
to the World Health Organization, a “core medicine,” essential for any nation’s pharmaceutical store. The strange thing is,
it doesn’t work unless you know you’re taking it.
In 2003 a paper in
Prevention and Treatment
reported that diazepam had no effect on anxiety when it was administered without the patient’s knowledge. In an extraordinary
experiment, researchers in Turin split a group of trial subjects into two. One half were given diazepam by a doctor who told
them they were being given a powerful antianxiety drug. The other group were hooked up to an automatic infusion machine and
given the same dose of diazepam—but with no one in the room and no way of telling they had received the drug. Two hours later,
the people in the first group reported a significant reduction in their levels of anxiety. The second group reported no change.
“Anxiety reduction after the open diazepam administration was a placebo effect,” the researchers suggested.
A placebo is a medical procedure that has no medicine in it. A sugar pill, or a spoonful of sugar water, a saline drip—or
anything, really. A parade of doctors in white coats coming to your bedside to offer reassurances can be enough to trigger
the effect. The power of placebo comes from the deceptive message that comes with it. You are told (or you sense) this procedure
or ritual will have an effect on your body or state of mind, and if you genuinely believe it, taking the pill or the drink,
or in some cases just seeing the doctor, will produce exactly that effect. Witch doctors, shamans, and other purveyors of
the magical arts are known to deal in placebos. When they carry out a sham ritual to cure a paying believer, that cure can
work wonders. The same might be said of televangelists. And Western medical doctors, too; research has shown that white coats
and stethoscopes can produce surprisingly effective placebo effects—as can a good bedside manner. Doctors know that if patients
feel they are getting a suitable treatment, the treatment is enormously more effective.
In one sense there’s an easy explanation for all this: the chemistry of the drug is being augmented by chemicals secreted
in the brain—the effect of what Fabrizio Benedetti, the leader of the Turin group, calls “the molecules of hope.” The difficult
side of the new experimental evidence is that, where we once thought we had a handle on the placebo effect, it is now becoming
clear that we don’t.
In medicine, we have long been accustomed to accounting for placebo. Modern scientific medicine was constructed on the notion
of the
randomized double-blind, placebo-controlled trial
, where drugs have to perform better than a dummy pill or inert saline injection. Now, though, things aren’t so clear. Some
analyses of the data suggest that the placebo effect is largely a myth. What’s more, the medical system was set up assuming
not only the existence of placebo but also that its effects can be separated out from the chemistry of the drugs being tested.
It seems that assumption was false, and the edifice of the pharmaceutical trial may have to be dismantled. No wonder a recent
National Institutes of Health conference declared placebo research an “urgent priority.”
Benjamin Franklin, the father of rational, “evidence-based” medicine, must be turning in his grave. In 1785 Franklin headed
a commission to investigate the claims of “animal magnetism.” The Austrian physician Franz Anton Mesmer had entranced (hence
mesmerized
) Paris with his claims that magnets and glasses of water could be used to healing effect. Louis XVI wanted to know whether
these claims stood up, and some of the greatest scientists in Europe were commissioned to find out the truth. Their tests
were the first scientific inquiries to use blindfolds that prevented the subjects from biasing the results—the original “blinded”
trials really were just that. The commission’s report came out in 1785. Any healing effect is “really due to the power of
the imagination,” it said.
Interestingly, 1785 was also the year the term
placebo
appeared for the first time in a medical dictionary. It was the expanded second edition of George Motherby’s
New Medical Dictionary
, and the word, to Motherby, meant “a common place method or medicine.” Though that is not particularly damning at first glance,
it was most likely a negative label, meaning the medicine was trivial, or unimpressive, because the word already had a negative
connotation.
Placebo
, which means “I will please,” had come to signify insincerity, flattery, and profiteering since medieval times, when greedy
churchmen would take mourners’ money to sing Psalm 116 at funerals. The psalm begins,
Placebo Domino in regione vivorum
(I will please the Lord in the land of the living). By 1811, that negative connotation was well established; Robert Hooper
published his
New Medical Dictionary
with an entry for
placebo
that read: “an epithet given to any medicine adapted more to please than benefit the patient.” Little did the clinicians of
Hooper’s day know that a placebo might benefit patients just as much as it pleased them.
As often happens, that knowledge had been gained and lost before. It was certainly known to the ancient Greeks. In 380 BCE
Plato wrote
Charmides
, in which the Thracian king Zamolxis tells Socrates that the great error of the physicians of his day was the separation
of the soul from the body. Despite doctors’ best efforts, curing the body is impossible without flattering the mind, Zamolxis
says.
If the head and body are to be well, you must begin by curing the soul; that is the first thing. And the cure, my dear youth,
has to be effected by the use of certain charms, and these charms are fair words; and by them temperance is implanted in the
soul, and where temperance is, there health is speedily imparted, not only to the head, but to the whole body.
Plato was right; words are powerful. If you communicate that you are doing something—if you utter what the French psychiatrist
Patrick Lemoine calls the
incantation
—it can work wonders.
An example of an incantation, drawn from Lemoine’s experience, might be, “I’m going to prescribe you some magnesium that will
treat your anxiety.” Magnesium isn’t a licensed cure for anxiety, but magnesium deficiency produces symptoms similar to anxiety;
in a bizarre nod to the principles of vaccination, European clinicians often prescribe magnesium for anxiety, Lemoine says.
And not only are his patients satisfied; they get better—and relapse if the treatment is interrupted. Nearly 250 years into
the era of evidence-based medicine, the incantation is still a powerful force.
A
1954 paper in the
Lancet
declared that the placebo effect is only useful in treating “some unintelligent or inadequate patients”; that seems almost
laughable now. According to Ann Helm of the Oregon Health Sciences University, somewhere between 35 and 45 percent of all
medical prescriptions are placebos. That estimate was made in 1985. In 2003 a survey of nearly eight hundred Danish clinicians,
published in
Evaluation and the Health Professions
, found that almost half prescribed a placebo ten or more times per year. A 2004 study of Israeli doctors, published in the
British Medical Journal
, determined that 60 percent had prescribed placebos, more than half of them doing it once a month or more. Of the Israeli
doctors who prescribed placebos, 94 percent said they found them to be an effective means of treatment.
These are not pure placebos. The doctor can’t send you to a pharmacy to get a sugar pill; after all, you might read the prescription,
breaking the spell. No, doctors routinely prescribe medications that have a tiny bit of something useful in them—but its licensed
use is not to treat what is ailing you.
Despite being so commonplace, it is a practice that splits the medical community. It is seen by some as unethical—dangerous,
even. And not only is it practicing deception on a patient; it also forces other medical professionals to act as accomplices
to the placebo-prescribing physician. After all, what do you do with your prescription? You take it along to the pharmacist.
Your pharmacist then—willingly or reluctantly—tends to play along. An article in the
Journal of the American Pharmaceutical Association
even provides a script for their role. Realizing that a doctor has prescribed a placebo, the pharmacist should deliver the
medication with these words: “Generally, a larger dose is used for most patients, but your doctor believes that you’ll benefit
from this dose.” The pharmacist might then advise you of some possible side effects. Or not.
If this shocks you, you can be comforted by the fact that no one is out to fleece you. Neither your doctor nor your pharmacist
is getting away with some scam. They are simply doing what they can for your health. They know that you have faith in their
abilities; otherwise you wouldn’t have come for the consultation. And their abilities include the knowledge that placebos
work—though no one knows exactly why. You have faith in your doctor, and that faith can make you well. The nature of placebo
simply means that they have to practice a tiny little deception to help it happen. Is that wrong? There is no consensus on
the answer to that question.
WHILE
the ethical issues surrounding placebo have long been debated to no conclusion, the scientific basis of the effect is a relatively
new topic for research. The general conclusion here, it seems, is that the placebo effect is due to chemistry. The classic
demonstration involves inducing pain in subjects; the original work was done by dentists who had extracted molars from patients.
However, less drastic measures are possible. The only truly essential ingredient is a little deceit.
It all kicks off with the pain-racked patients receiving something like a morphine drip. Later, after the patients have begun
to associate the morphine with pain relief, you can subtly substitute saline solution for the morphine. The patients don’t
know their “morphine” is nothing but salt water and, thanks to the placebo effect, they report that their pain medication
is still working fine. That is strange in itself, but not as strange as the next twist makes things. Without saying anything
to the patients, you put another drug into the drip: naloxone, which blocks the action of morphine. Even though there is no
morphine going into the patients’ bodies, naloxone still stops the pain relief in its tracks; the patients, oblivious to all
that has gone on, now report that they are in discomfort again.
The only plausible explanation is that the drug that blocks morphine’s pain-relieving power also blocks the saline’s (placebo-based)
pain-relieving power. Which means the saline really was doing something—it wasn’t all in the patient’s imagination. Or at
least it means that imagination can have a physiological effect.
When the dentists first performed this trick, they attributed the placebo effect to a stimulation of the body’s endorphins,
natural opioids that act using the same biochemical pathways as morphine. The expectation of pain relief was enough to trigger
an endorphin release that did the job, they concluded. Then the naloxone blocked the endorphins; that’s why the pain came
back. It turns out to be more complicated that that, however.
What was once considered nothing more than the fancies of the imagination is a real, repeatable, and multifaceted biochemical
phenomenon. The placebo effect pulls out all the stops; the expectation of pain relief can stimulate all kinds of natural
pain-relieving chemicals. Use ketorolac, a painkiller that works via a completely different chemistry from that of morphine,
in the conditioning, then replace it with saline. The addition of naloxone does nothing there because the placebo pain relief
is provided not by endorphins but by some other natural painkiller that your body produces. The stimulation of hormones that
work in the same way as the painkiller sumatriptan is one example. The phenomenon even depends on how much pain the patient
is expecting to feel. Tell ready-conditioned patients they are getting morphine that is more dilute than usual (when in fact
they were getting nothing more than saline), and introduce naloxone. Again, it doesn’t block the painkilling effect of the
saline because the expectation of reduced pain relief has triggered some alternate mechanism. What everyone thinks of as “the
placebo effect” turns out to be a whole array of different effects, each with a unique biochemical mechanism. Our brains can
fool us in any number of ways.
THOUGH
all this seems completely convincing—by now, we are surely confident that the placebo effect is a real phenomenon—there is
a fly in the ointment. In 2001 two Danish researchers published a landmark paper in the
New England Journal of Medicine
. Asbjorn Hróbjartsson and Peter Gøtzsche had begun to get suspicious about claims of the efficacy of the placebo effect.
Everywhere they looked—in textbooks, journal papers, and magazine articles—authors were quoting a number the pair couldn’t
quite believe. According to almost everything in the medical literature, 35 percent of patients would get better if told a
dummy treatment they had been given was real.