"The Wonder Pill"
premieres February 18, 2003
A DIFFERENT WAY TO HEAL
LIFT THE BLUES
SNUFFING THE SNIFFLES
ALAN ALDA This may or may not be real acupuncture. And this
may or may not be a real drug. Now here's a provocative
question. Does it matter?
ALAN ALDA (NARRATION) Our
show is about placebos - sham medical treatments masquerading
ALAN ALDA I feel it. Yeah. I felt it. Have
you seen people markedly improved on the placebo?
Yes. We've seen complete cessation of depression on
ALAN ALDA (NARRATION) Placebos may not
only help you feel better - new research suggests they
can change your brain.
SEDRIC BELL It's like trickery,
you know? They tell you they've given you whisky but
ALAN ALDA (NARRATION) So if placebos work so well…
RANDREA MAJORS Oh, yeah, I'm really glad I got it.
ANDREW LEUCHTER I think it's worth it.
ALAN ALDA (NARRATION) What does it mean for how your doctor
ALAN ALDA I feel better already. I'm Alan
Alda. Join me as Scientific American Frontiers investigates
the power of the placebo in The Wonder Pill.
A DIFFERENT WAY TO HEAL
ALAN ALDA Imagine a scene like this: You come into your
doctor's office with a problem that won't go away. You've
had the usual round of blood tests and maybe some expensive
scans. Finally the doctor is ready to prescribe some
medicine for you. And she gives you a choice: some heavy
hitting drugs with risks of side effects, or this: a
pill which she says is proven effective in some one-third
to one-half of patients taking it. It's been in use
for years. It's been through thousands of clinical trials
and has minimal side effects. No one's quite sure how
it works, although some new research has been coming
up with interesting ideas about how it affects the brain.
Oh, and one more thing -- and she sort of slips this
in there -- it doesn't actually contain any active drug.
So, what do you think? Would you give it a try? The
pill you were offered was a placebo, a sugar pill. Placebos
are a hot topic in medicine right now. The placebo effect
is the often positive response that patients get to
a sham medical treatment -- not just a fake pill, but
in some cases even a fake surgical procedure. Recently
researchers have discovered that in some cases, placebos
cause physical changes in the brains of people taking
them. This has led to surge of interest in understanding
the placebo effect. And while your doctor may never
offer you a sugar pill instead of the real drug, there's
real interest now in trying to turn the placebo effect
into a useful therapeutic tool. Which is why we're starting
our show here: among the graves of people who died often
very young, from diseases that pre-scientific medicine
was unable to cure. This is the grave of Dr. Harriet
Hunt, one of the first women physicians in the country.
What was it that Harriet Hunt and her mostly male colleagues
in the healing profession were able to offer their patients?
ALAN ALDA (NARRATION) The short answer, obvious in the
gravestones here at Mount Auburn Cemetery in Cambridge,
Massachusetts, is not much. There are hundreds of graves
of children - and many of the adults died in their 30s
and 40s. Most of these deaths were from infectious diseases
like cholera and tuberculosis that medicine was once
helpless against. But as long as people have been getting
sick, there have been people who claimed to be able
to cure them. We invited Anne Harrington and Charles
Rosenberg, both of nearby Harvard University, to help
us understand what kept doctors in business.
Over the centuries, what have people actually been given
to make them feel better?
CHARLES ROSENBERG Well, lots
of different things. But I think there's a real continuity.
People always expected if they were sick to take a drug.
This book was published in 1656. And it was a very very
popular English book called The English Physician Enlarged.
It has "369 medicines made of English herbs that were
not in any impression until this." This is an herb called
Allheal. It was also called Hercules Allheal and Hercules
Wound-Wort. "It is under the dominion of Mars, hot,
biting and choleric. It kills the worms, helps the gout,
cramp and convulsion, provokes urine, and helps all
joint aches. Helps a cold grief of the head, the vertigo,
falling sickness and lethargy. The wind colic, obstructions
of the liver and spleen. It is excellent good for the
grief of the sinews, itch, sores and toothaches.
ALAN ALDA Grief of the sinews?
CHARLES ROSENBERG That would
probably mean probably arthritis or something like that
-- diseases of the joints.
ALAN ALDA You know what's
wonderful about this? It's so authoritative, it tells
you about the planets that govern it. It's a lot like
saying, proven in clinical trials…
ALAN ALDA (NARRATION)
Some of these herbal remedies may have had consequences
- acting as a diuretic, say, or making your pulse race
- but it's unlikely they actually cured many diseases.
ALAN ALDA Was there anything that worked, a hundred,
a hundred and fifty years ago?
CHARLES ROSENBERG Well,
the issue is worked, because that sounds like a simple
word, but it's a complicated word. Because when we say
worked, we put a kind of physiological, modern kind
of notion: does it have a physiological effect, make
a disease change its course, make the body operate differently.
But if you think of worked as having a patient feel
differently or have the patient feel that someone was
taking care of them, then medicines worked in a different
kind of way.
ALAN ALDA (NARRATION) This different kind
of way is what our show is about - the mysterious chemistry
brewed up between doctor and patient that works even
when the medicine is what today we'd call a placebo
- an inert substance masquerading as medicine. While
most doctors in the past would certainly not have thought
as their remedies as placebos, there was a time, right
before the advent of modern medicines, when placebos
had an acknowledged place in the physician's medical
ANNE HARRINGTON Back in the '30s and '40s when
we lived in a more paternalistic culture, doctors would
keep bottles of placebos on their shelves. In fact,
they had these mail-order catalogues that advertised
placebos of different sizes and shapes and colors. And
there were professional conversations about the yellow
ones that were particularly good for patients who were
suffering from one kind of thing. Blue would be good
for sleeping pills. Red were good for pick-me-uppers.
Because these things had a symbolic logic that doctors
were aware of. And doctors were prepared to give these
pills to patients in the 1930s and '40s because it was
felt, in a sense, that doctor knows best. Patients didn't
need to have full consent and information about what
was going on. We live in a different kind of society
ALAN ALDA (NARRATION) It's a society where housecalls
have been replaced by the 10-minute HMO appointment,
robbing the doctor - and so his patient -- of what was
once medicine's only effective treatment.
I sometimes think of it as the white feather effect.
In the Disney film, Dumbo needs a white feather in order
to fly. He believes the white feather… you haven't seen
this film, have you?
ALAN ALDA I've haven't seen it
since I was five. So you're looking at a blank face
here, I'm sorry.
ANNE HARRINGTON In the animated Disney
film, Dumbo was an elephant with gigantic ears. And
he flaps his ears and he can fly. He believes he can
only fly when he carries a white feather in his trunk.
ALAN ALDA Well, that's true for me, too.
And one day, the white feather falls from his trunk
and he realizes he was doing it all along. So the placebo
is the trick that enables us to open up things inside
ourselves through mechanisms that aren't well understood
but are beginning now to be elucidated somewhat in the
laboratory. But we do it to ourselves.
ALAN ALDA (NARRATION)
In this show we are going in search of Anne Harrington's
white feather, trying to rediscover the trick that allowed
19th century physicians like Harriet Hunt to turn a
placebo into a wonder pill -- and that even in the medicine
of the 21st century, can perhaps still cast its spell.
BRAINWAVES LIFT THE BLUES
ALAN ALDA (NARRATION) Of my two companions here at the
University of California in Los Angeles, one succumbed
spectacularly to the spell of the placebo effect - while
the other decidedly did not. They each answered an ad
recruiting people suffering from severe depression for
a study of antidepressant medications. As is usual for
such studies, some of the patients were assigned to
a control group, receiving placebo pills instead of
the real thing
ALAN ALDA They told you that you might
be on the medication, or you might be on a placebo.
JANIS SCHONFELD M-hmm.
ALAN ALDA And you assumed you
were on the medication.
JANIS SCHONFELD I certainly
ALAN ALDA When did you make the transition from
thinking--I wonder what I'm taking. You must have thought
that, didn't you?
JANIS SCHONFELD No, I never did.
ALAN ALDA Oh. It sounds like they didn't have to give you
JANIS SCHONFELD No. Because I was feeling
so much better, I was convinced I was on the medication.
ALAN ALDA Are these the pills that the patients take?
NURSE These are the pills, the study material.
ALAN ALDA Which pills are these?
NURSE Well, we don't know.
ALAN ALDA Oh, so they all look exactly the same.
They all look exactly the same.
ALAN ALDA Of course
ALAN ALDA (NARRATION) The physician running
the study is Dr Andrew Leuchter.
ANDREW LEUCHTER When
somebody comes to this big imposing research institution
and they see warm and caring nurse in a white coat,
they have an expectation they're going to get better.
They believe they're going to get helped. And since
we're conditioned to believe that sugar pills can't
possibly get you better, we tend to think those are
ALAN ALDA (NARRATION) Janis Shonfeld
had never taken antidepressants before. But Frank Strauss
had - and to be eligible for the UCLA study had had
to stop taking his old medication a couple of weeks
before the trial began.
FRANK STRAUSS When I get depressed,
it's debilitating. I can't see it to walk downstairs;
I have to hold on to the railings. I can hardly leave
my apartment. I get zero sleep 'cause my heart beats
all night long. And I just lay there and watch the sun
come up, and it's like, the worst.
ALAN ALDA How did
you feel when you knew it was a placebo?
You know, I thought it was a really cruel joke, is what
I thought. I thought, here's my whole life in the balance,
and they're giving me something that, all of a sudden
I'm getting like screwier by the moment. And I was angry
to say the least. It never even entered my mind that
they were giving me a placebo, because, I'm like, here's
this basket case, you can't possibly give me a placebo.
You know, it's like, what are you thinking?
(NARRATION) Frank may not have responded, but many studies
have shown that some 40 per cent of patients with depression
feel better on placebo - and in this respect, the UCLA
trial was typical.
ALAN ALDA Have you seen people markedly
improved on the placebo?
MICHELLE Yes. We've seen complete
cessation of depression on the placebo.
The patients who got better on placebo, and the patients
who got better on medication, couldn't be distinguished.
At the end of eight weeks, we told everybody what they
were getting. So at the end of eight weeks, they knew
they'd been getting either placebo or medication. The
patients who got placebo, almost all of them within
a month of the end of the study, had relapsed. Because
as soon as they knew they were on placebo, most of them
said, "you know, maybe I'm not feeling that good."
ALAN ALDA "Maybe I don't feel that good." Yeah.
ALAN ALDA "I'm still depressed."
(NARRATION) But while Andy Leuchter's study was unremarkable
in finding that many patients - like Janis - responded
to placebo, it was pioneering is what it found out about
her brain. Like the other subjects in the study -- including
those taking real antidepressants - Janis came in for
regular EEGs. Leuchter was trying to see if he could
spot early changes in the brain waves of patients on
medication. Often patients don't get any benefit from
an antidepressant for several weeks, and Leuchter was
hoping to find a brain wave signature that would predict
if an antidepressant is going to help. Early results
looked promising. Depressed patients usually have less
activity than normal in their prefrontal cortex, and
in the UCLA trial, antidepressants that worked lowered
the activity still further. A puzzling finding, perhaps,
but still potentially a useful predictor of an effective
TECHNICIAN Try to think about something that
keeps you alert.
ALAN ALDA (NARRATION) But the big surprise
came in the brain waves of patients like Janis Schonfeld,
who felt better even though they were on placebo.
ANDREW LEUCHTER What we found was, in patients that got placebo
when they got better, this same region of the brain
here, actually showed an increase in activity. It was
the opposite pattern. It took a little bit longer to
come on. But over the span of eight weeks of treatment,
there was this augmentation of activity in the front
of the brain in patients who felt better on placebo.
ALAN ALDA Now wait, this is a little hard to get. They
take the antidepressant pill, the real pill. And, they
feel better and they get lower activity in that part
of the brain.
ANDREW LEUCHTER That's correct.
Then they're given the placebo, and they feel better,
but they get heightened activity in that part of the
brain. Now originally I would imagine you would have
thought the lowered activity was related to feeling
better. How is it that--never mind that they took the
placebo--how is it that they have this heightened activity
here, but they feel better. How could that take place?
What do you think is going on there?
As you yourself said, the brain is extraordinarily complex.
I think what it all gets down to, is there are multiple
pathways to improvement. There's not just one way to
get better. Now, it may not be as robust an improvement
as a lot of patients would get with medication. And
we don't think it lasts as long. We think it's a more
fragile kind of improvement. But it's important because
this other way to feel better that some patients are
able to activate.
JANIS SCHONFELD My mood lightened,
definitely, and if you've ever suffered from depression,
and I have been diagnosed with clinical depression beforehand,
there's such a weight that you carry, it feels like
it's on your shoulders and on your head that, to have
that lifted, it almost feels like you can run… you can
run a marathon. Or you can run quickly. And that's how
I was feeling.
ALAN ALDA That's amazing. And yet it
was a sugar pill.
JANIS SCHONFELD Yes.
ALAN ALDA (NARRATION)
Andy Leuchter's discovery that placebos can actually
change the brains of people who feel better is dramatic
confirmation of the fact that - while it may all be
in the mind - the placebo effect is real and measurable.
ANDREW LEUCHTER The importance of this work, from my
perspective, is, we can help figure out what leads to
healing. That's really what this is all about is healing.
There's something that some patients are able to activate,
just by coming into treatment, getting inert treatment,
taking a placebo pill. Some patients are able to feel
better. What is it that is leading to that placebo effect?
Is it a stronger bond between those patients and their
doctors? Is it they have more positive expectations?
They come in believing they're going to get better?
If we can distill that out and apply it more broadly,
maybe we can help all treatments be more effective.
And that's really one of the goals of this is to tease
out something about the placebo effect that we could
apply more broadly.
ALAN ALDA (NARRATION) Leuchter's
hunch is that this something -- the essence of the placebo
effect -- lies in that most ancient of a doctor's skills:
the healing power that flows from a caring physician
to a receptive patient.
ANDREW LEUCHTER Hi, I'm Dr Leuchter.
ALAN ALDA Hi.
ALAN ALDA (NARRATION) Which is why I'm
in his consulting room, playing the role of a patient
ANDREW LEUCHTER So how are you doing
ALAN ALDA Well, I feel a little low.
(NARRATION) Leuchter is shortly to begin a new study
in which as well as getting either a real antidepressant
or a placebo, patients will also be randomly assigned
to either a detached and businesslike physician, or
- as Andy is here -- a warmer and more empathic one.
ALAN ALDA I still don't sleep well. I wake up and then
I can't go back to sleep.
ANDREW LEUCHTER I'm sorry
to hear that. Okay. Are you having a problem sleeping
ALAN ALDA Yeah. Every night. Yeah.
ANDREW LEUCHTER Okay. I'm going to go down a list of some questions
that I have to ask you here to see how you're doing,
okay? Would you say you feel the depression everyday?
ALAN ALDA Oh yeah, yeah.
ANDREW LEUCHTER Okay, okay.
ALAN ALDA You know, I wake up with it. Wake up.
ANDREW LEUCHTER Right. Is there any time of day it's worse
than other times of day?
ALAN ALDA Ah--I think in the
ANDREW LEUCHTER Okay, okay. Do you feel that
the treatment has been helping you?
ALAN ALDA Not to
ANDREW LEUCHTER I'm gonna jot down a couple
notes here if that's alright.
ALAN ALDA (NARRATION)
In his "old doc Brown" persona, the doctor in the new
study will strive to build a bond with the patient,
asking open-ended questions, maintaining eye contact
even when making notes, and generally being as supportive
ALAN ALDA It doesn't seem to be working.
ANDREW LEUCHTER I'm sorry to hear that. Sometimes people
do feel that way. It's important to remember that sometimes
the medication can take a little while to work. So you
might not notice the effect right away, but you may
notice in the next week that you start to feel a little
ALAN ALDA But you know, it feels like nothing
ANDREW LEUCHTER Let me just ask you a couple
more questions here before we close. How has your appetite
ALAN ALDA Well, I eat when I'm depressed. I also
eat when I'm feeling good.
ANDREW LEUCHTER Okay. You
still have some sense of humor.
ALAN ALDA Well, yeah.
ANDREW LEUCHTER I think that you should stick with this.
I think this is something that can help you. I hope
you're willing to continue. And give it more time and
see if, in fact, this treatment can help you.
Well, if you think so.
ANDREW LEUCHTER I think it's
ALAN ALDA Okay. I feel better already.
ANDREW LEUCHTER Okay!
ALAN ALDA (NARRATION) In his brisk HMO-doc
persona, the doctor in the new study will still be polite.
ANDREW LEUCHTER Hi, I'm Dr. Leuchter.
ALAN ALDA Hello.
ANDREW LEUCHTER Good to see you. I've got a few questions
for you today. I have to take some notes and see how
ALAN ALDA (NARRATION) But this doctor
will be focused on getting the clinical information
he needs rather than trying to discover the needs and
concerns of his patient. He'll make less eye contact.
ANDREW LEUCHTER So your mood's been down, depressed?
ALAN ALDA Yeah. I feel like nothing matters…
(NARRATION) His questions will be more pointed.
ANDREW LEUCHTER Appetite?
ALAN ALDA Well, I eat. But I'm not….
ALAN ALDA (NARRATION) Over the course of the study,
patients will have their brain waves measured to see
if there's a difference between the brains of the patients
who get the warm doctor and those who get the cooler
ANDREW LEUCHTER Okay. Sleep?
ALAN ALDA Yeah, I
don't sleep much.
ALAN ALDA (NARRATION) Andy Leuchter
is the first to acknowledge that a study like this is
fraught with problems, not the least of which is that
the doctor-patient relationship is a two way street.
For instance, for whatever reason, I find myself slightly
preferring this more detached doctor than the one who
was supposed to be warm and fuzzy.
ANDREW LEUCHTER Well,
I think that taking this medication is an important
part of your recovery. It can help you stay well, so
we need to continue with what we're doing right now.
ALAN ALDA (NARRATION) But what's most fascinating about
Andy Leuchter's planned study is that it will be one
of the first to try to bring the tools of research medicine
to the study of medicine's art - to try to quantify
what has always been regarded as mysterious and beyond
ANDREW LEUCHTER Okay, very good. Thanks
for coming in.
ALAN ALDA Okay. I don't know. What do
you think? You think the other guy was better?
ALAN ALDA (NARRATION) When the original UCLA study was over,
patients on the placebo were offered a real antidepressant,
free of charge. Janis Schonfeld took up the offer and
made a full recovery from her depression. Frank Strauss
never made it beyond the first few days on placebo.
FRANK STRAUSS I say this sort of in jest, but I was
too screwy to even stay with the study. So they sent
me down the road to another place. They said, we can't
help this guy, go down here. So I went down--.
ALAN ALDA You finally want to get a positive ending to this.
You finally did get on a medication that helped you.
FRANK STRAUSS I did, yeah, right. Down from another
organization. Finally I balanced it out and I've had
the best years of my life since then. It's amazing what
all that's happened. It's totally changed.
So it sounds like two different testimonials to say
about placebos. Yours isn't so bad, but you don't seem
to be a fan of placebos.
FRANK STRAUSS No. It's kind
of like being in the desert, thinking you're getting
a bottle of water, instead you're getting sand or something.
JANIS SCHONFELD It almost sounds like, really, one of
the things that effects your reaction is your expectation
going into it, don't you think? I mean, you had another
need and want it than I did. Yeah.
FRANK STRAUSS I was
interested in finding something that was a little better
than the ones I was taking. So I thought this new--whatever
it was would be the miracle drug that would fix me up.
All of a sudden I get rich and find the girl of my dreams.
All over night, you know.
ALAN ALDA The have a pill
FRANK STRAUSS I was looking for it, you know?
ALAN ALDA (NARRATION) We're in Vancouver, British Columbia,
where Sedric Bell is renewing a love affair with the
latest version of a car he first drove over 40 years
ago. Back in his native England in the 1960s, Sedric
had great success racing Minis on some of Britain's
major circuits. He emigrated to Canada 20 years ago.
But then Parkinson's Disease stuck, stiffening his limbs
and making movement difficult. Now it takes 16 to 20
pills a day to give him control over his body - and
the dosage has to be tuned precisely.
SEDRIC BELL If
it cuts in good, I'm as fit and agile as anyone. I can
run, jump, anything like that. But when you're stiff,
you're just as stiff as a board. If you're a little
bit over my head's flopping all over, there's no control
over my muscles. People say, "relax." I can't relax.
There's no connection. My head can't tell my arm and
leg to relax. It's just lock solid until the medication
JON STOESSL Just relax your head, let
it go loose. Okay, very good. Now just open and close
your hands, would you please?
ALAN ALDA (NARRATION)
Sedric was recently one of the Parkinson's patients
volunteering for a study conducted by Jon Stoessl and
his colleagues at the University of British Columbia
JON STOESSL Now open and close your left hand.
ALAN ALDA (NARRATION) Like Andy Leuchter at UCLA, Jon
Stoessl planned a study of real drugs - but ended up
instead with startling new evidence about how placebos
affect the brain. The tests Sedric's going through are
standard for assessing the severity of a patient's impairment
due to Parkinson's. His right side is more affected
than the left, showing up mostly in his slow and difficult
movements, but also - especially when he's stressed
- in the tremor most of us associate with Parkinson's.
JON STOESSL The tremor is often not a prominent feature,
even though it's a very common feature, it's often not
the most prominent feature for people and, in fact,
it is very uncommon for it to be the disabling feature
of Parkinson's. The disabling feature is the poverty
of movement, the slowness of movement.
SEDRIC BELL It's
rare that I shake. See. It's very rare. The only time
I notice it is on the transition of the medications
when it's coming on and going off. I may get a little
bit of --. It could be any part of the body. And then
it just settles down when it goes in. And generally
I should be good for three hours with the medication
ALAN ALDA (NARRATION) The medication is levodopa,
which in Sedric's brain helps replace dopamine, one
of the brain's communication chemicals, and essential
for controlling movement.
JON STOESSL When we start
treatment for Parkinson's, people get a good response
for a few years, or several years. But after a few years,
they get into the trouble, often with the benefit of
the medication wearing off before the next dose is due.
So we were doing studies to try and better understand
why that might occur, and those studies involved looking
at the amount of dopamine that's actually available
to the nerve cell.
ALAN ALDA (NARRATION) Measuring how
much dopamine is released in response to medication
involves a trip to the hospital basement…
we are at Positron Emission Tomography.
ALAN ALDA (NARRATION)
Where Sedric has spent long hours lying in the PET scanner.
SEDRIC BELL The bed knows me.
NURSE It does. Yes.
ALAN ALDA (NARRATION) During this time, his head must be
perfectly still. A mask that's flexible when warm and
can be molded to his face dries into a rigid head restraint.
TECHNICIAN And as it cools it's going to harden to the
shape of your face.
ALAN ALDA (NARRATION) Parkinson's
is one of those conditions - like depression - that
in many patients can be alleviated - at least for a
while - by a placebo. So it was especially important
to include in the trial of active dopamine-releasing
drugs a placebo control.
JON STOESSL They were told
explicitly that they would be receiving three or four
injections of drug. One of which would be an inert substance.
They were not told in which order those injections were
to be given.
ALAN ALDA (NARRATION) As expected, the
PET scans showed an increase in dopamine release in
the brains of subjects receiving an active drug. But
what was not expected was that there was just as big
a dopamine release in the brains of some patients -
like Sedric Bell - when the injection was of an inert
placebo, a saline solution.
JON STOESSL It was initially,
certainly a big surprise, and then when we stopped to
think about it it became somewhat less of a surprise
in that it's been recognized for many years that dopamine
is somehow involved in reward mechanisms in the brain.
So when we have things that we enjoy or that we look
forward to….Drug addicts, for instance, get their reward
related to dopamine release. So if you think about it,
the placebo effect has everything to do with the expectation
of benefit and that, I think, could be very analogous
TECHNICIAN Okay, we're going to bring you
out now. You did well. Good job.
ALAN ALDA (NARRATION)
Making the Vancouver study even more remarkable was
the fact that the placebo released dopamine in precisely
the same place in the brain as do the real drugs - just
where it's needed to activate the pathway that controls
movement. And to top it off, volunteers like Sedric
whose PET scans revealed dopamine release in response
to placebo also improved when run through the standard
test battery - again, just as you'd expect if he'd received
NURSE So you're a little better than
you were earlier.
JON STOESSL I think this is really
a tremendous example of the mind controlling the body.
Those of us who work in neuroscience regard these as
closely linked. We don't really think that there's something
different about the mind. But this is really the classic
example of how your expectation of something, your attitude
towards something can materially affect the physical
outcome, that it's not just loosely how you think about
whether or not you responded. But there is actually
a physical explanation.
SEDRIC BELL It's like trickery,
you know? They tell you they've given you whisky but
they haven't. It's great surprising that things turned
out like that. To take something that activates your
dopamine cells. And it isn't supposed to do anything
like that at all. It's truly amazing.
ALAN ALDA (NARRATION) We've seen how the expectations
aroused by placebos can affect the brain. Those same
expectations can make drug research an often very messy
business. These volunteers, whose noses are being rinsed
out with a saline solution, are being paid to catch
ALAN ALDA If you wash his nostrils out he'll
have a better chance of catching cold?
Mm, mm. 'Cos the nose'll be nice and clean.
This is a horrible thing to learn first thing in the
morning. OK, go ahead. I mean I would have thought that
getting your nose clean -- like, you know, they say,
keep your nose clean -- I would think that would help.
ALAN ALDA (NARRATION) The man dispensing the colds is
Ronald Turner. What he's carefully placing up the nostrils
of his volunteer subjects here in Charleston, South
Carolina, is a strain of rhinovirus, one of the commonest
causes of the common cold.
ALAN ALDA Now you already had one of these?
ANNE SANDERS I had one. I had one already.
ALAN ALDA So how many do you give?
Two. We just go around twice.
ALAN ALDA You really want
to make sure you make these poor people sick.
RONALD TURNER OK, this is the same as before.
ALAN ALDA (NARRATION)
Actually, Ron Turner is hoping some of his volunteers
won't get sick…
RONALD TURNER Here we go again.
ALAN ALDA (NARRATION) …because for the last two weeks some
of them have been taking twice-daily doses of one of
those herbal extracts that a lot of us believe helps
fend off or shorten a cold.
RONALD TURNER Some are getting
active medication, some are getting placebo. Everybody
gets the virus.
ALAN ALDA Now do you know, are you aware
of who's getting the placebo and who's getting the medication?
RONALD TURNER No, we're all blinded.
ALAN ALDA You don't
have any idea?
RONALD TURNER No.
STEVE SCIBELLI This
is what they look like.
ALAN ALDA The famous ju-ju bead
medication. So what do you think is in there?
STEVE SCIBELLI I'm really not sure. Hopefully some medication
that will take care of me. But for all I know it could
be just sugar pills.
ALAN ALDA (NARRATION) This need to ensure no one knows
who's getting what is absolutely critical in a trial
like this. It's especially important that the volunteers
aren't picking up any clues from how the pills taste
or make them feel.
RESEARCHER Do you think you were getting the active
medication or the inactive medication?
ANNE SANDERS I think I was getting the inactive.
ROBERT BOZARD I have no idea. I really don't. I had
no side effects, no symptoms of any kind either way,
RESEARCHER OK, give me a guess.
ROBERT BOZARD Active.
RANDREA MAJORS Inactive.
DAVID MIN I think I was getting inactive.
EDDIE GORDAN Active.
RESEARCHER And why?
EDDIE GORDAN I don't know. It was just that whenever
I took it I felt, like, fuller.
MIKE LEWIS I would have to say the active medication.
RESEARCHER Why would you say that?
MIKE LEWIS It'd kind of depress me if I was having
the other medication.
LINDSEY DUGAN I would say the inactive.
RESEARCHER Why would you say that?
LINDSEY DUGAN Just because I didn't feel any difference.
ALAN ALDA Do you think it matters whether or not you
believe you're taking the active ingredient?
LINDSEY DUGAN Yes. I think if I thought I was on it,
I would definitely experience a placebo effect and feel
better than maybe I should. And thinking that I'm not
on the medication I might be more inclined to feel the
symptoms more severely.
ALAN ALDA (NARRATION) Lindsey's right:
if people are able to figure out what they're getting,
then it could dramatically influence the results of
STEVE SCIBELLI I'll go with active.
RESEARCHER Why do you say that?
STEVE SCIBELLI I'm hopeful.
ALAN ALDA (NARRATION) In fact, in Ron Turner's opinion, the
placebo effect - and in particular the difficulty of
eliminating it - is why we're all so confused about
popular cold remedies like echinacea or vitamin C. Take
one of my favorites, for example, zinc lozenges.
ALAN ALDA Is it true that, even when you're not in
a study, when you're just sick and taking this lozenge,
the fact that it tastes funny, might increase the placebo
effect for you and may help you feel better sooner.
Is that possible?
SCIENTIST Yeah, I think that's the old-It's gotta taste
bad to be good-concept. You know-good medicine has got
to be, in some way-onerous. There's got to be some penalty
for getting better faster.
ALAN ALDA If we in fact believe that on some deep level,
then it might be a self-fulfilling prophecy. Is that
right? Is that the way it might work?
SCIENTIST Sure. I think clearly that's a possibility.
And, in fact, you might say, "well, so what?" If that's
the benefit you get, that's good.
ALAN ALDA Alright, okay, I'm desperate now. What did
you put in the study today? Maybe I can take that. I
mean even before you find out in your study that it's
no good, I'll have a couple of colds that I can use
it on and get the placebo effect.
CAROLINE SWAIN Definitely have the cold. The cold,
I have it.
MIKE LEWIS I don't feel ill at all. If I'm supposed
to be ill right now, I'm not ill.
UNKNOWN I have the cold.
ALAN ALDA (NARRATION) Three days have passed since
our volunteers were infected with the cold virus. They've
been reporting in every morning since.
RESEARCHER It's been about 72 hours since the inoculation.
Do you think you received a cold?
STEVE SCIBELLI Yeah, I do. I definitely had it yesterday.
RESEARCHER OK, I want you to rate your symptoms this
morning, based on the severity since your last visit.
Any symptoms of sneezing?
STEVE SCIBELLI I'd say about a two.
RESEARCHER OK. Runny nose?
STEVE SCIBELLI One.
RESEARCHER Nasal stuffiness or obstruction?
STEVE SCIBELLI Two.
ALAN ALDA (NARRATION) There are a dozen symptoms on
the list -- enough to get a pretty objective measure
of the severity of the cold.
RESEARCHER Definitely getting a little bit worse,
STEVE SCIBELLI Yeah.
RESEARCHER OK, you can go on back and get your nasal
ALAN ALDA (NARRATION) The nasal wash will reveal how
strongly the virus took hold. Meanwhile we wondered
how our volunteers feel now about whether they are on
the test medication or the placebo.
ANNE SANDERS I think I'm receiving just a placebo.
DAVID MIN I think it kind of got better because I
was taking… I'm not sure whether I had that medication
or not, but I think I did.
EMILY WORREL I believe I had the inactive medication.
Because otherwise I think I wouldn't have got the cold
or it wouldn't have been as severe.
KATHERINE HOEFT Based on how mild my symptoms are,
I think maybe I did get the active.
RANDREA MAJORS Oh, yeah, I'm really glad I got it.
Otherwise I'd be walking around with tissues hanging
out of every pocket, and just not a pretty sight.
LINDA MIELCAREK I think I got the inactive medication
because I've been getting worse as the days go on.
LINDSEY DUGAN I guess I got the active medication,
'cos all I've had is a runny nose and that's it.
ALAN ALDA (NARRATION) Surprise, surprise -- most of those
with the worst colds thought they were on the placebo,
while most subjects with mild colds guessed they had
the medication. But in fact it was all in their heads.
Later, when who got what was matched up with the severity
of their infections, there was no difference between
those who got the test substance and those who got placebo.
That's right, the mystery herbal ingredient in those
big brown pills did no better - and no worse - than
the placebo -- a judgment Ron Turner also makes about
most other popular cold remedies.
ALAN ALDA You know
what's funny about this? And this is just totally personal.
I'm going to keep taking this stuff, because I haven't
got any other feeling of control over the cold. And
for me getting a cold, because I have to use my voice
in my work, is something that…. I'll clutch at straws.
How does that strike you as a scientist?
Well, I guess I don't have any problem with that. As
I said, my job here is to try to figure out whether
there is a biologic effect. Whether people choose to
use that information or whether they get some benefit
-- whether it's psychological or mental -- that's fine.
You know, the saying is of course that if you take this
medication you'll get over your cold in 7 days and if
you don't it will take a week. So…
ALAN ALDA That's
the best you can come up with? After all these years?
RONALD TURNER Well, I think we're doing better than
that. I think we're doing better than that.
ALAN ALDA (NARRATION) One of the most mysterious of
medical treatments is acupuncture. Thousands of years
old, still practiced widely in China, it has in recent
years edged into mainstream medicine even here in the
ACUPUNCTURIST The patient is suffering
from insomnia. Maybe due to stress, maybe due to heart
Qi deficiency. Because he is a student he has a lot
ALAN ALDA (NARRATION) Acupuncture's growing
popularity comes despite its striking contrast to conventional
western medicine. It's theoretical underpinnings, involving
the manipulation of a force called Qi through energy
channels in the body, has no known basis in how Western
medicine believes the body to work. People go to acupuncturists
for one good reason -- many feel better as a result.
But while some scientific studies suggest acupuncture
may relieve pain by releasing natural painkillers in
the brain, the power of acupuncture to heal some people
of some conditions remains mysterious. Mysterious, exotic
and tantalizingly different from establishment medicine
- just the formula to entice a 1960s student radical
to China to study traditional Chinese medicine. Ted
Kaptchuk spent several years there, returning to the
United States skilled in herbal medicine as well as
acupuncture - which he practiced here with a success
that surprised even him.
TED KAPTCHUK I said to myself,
I'm not as good as practitioner, I'm not as good as
acupuncturist as my teachers. But I kept seeing people
get better much quicker than I saw in clinics where
I worked in China. And it occurred to me that maybe
the exoticness, the ritual, the complexity, talking
about mysterious forces may indeed elicit a ritual response,
or elicit a kind of magical capacity for self-healing
that's actually greater.
ALAN ALDA (NARRATION) Ted Kaptchuk,
now firmly back in the medical establishment at Harvard
Medical School, wondered if this "magical capacity for
self-healing" has more to do with the placebo effect
than with Qi. So he's designed an elaborate study of
RSI - repetitive stress injury, or carpal tunnel syndrome
- the pain many people experience after hours spent
at a keyboard. Some of the patients in the study will
get a pill - either a real drug or a look-alike placebo.
Others will get acupuncture - either real or a placebo,
sham acupuncture. What Kaptchuk really wants to find
out is how the two placebo treatments stack up against
each other: is the placebo effect of sham acupuncture
- with all its rituals and mystery intact - more effective
than the placebo effect of simply popping a pill?
TED KAPTCHUK And that's what's unusual about this particular
experiment. It's saying, no longer do we take the placebo
effect and just throw it in the waste paper basket.
Let's look at these placebo effects as a major question,
a major component of medicine, a major consequence in
health care. To what extent does the ritual, one particular
ritual, in this case the ritual of acupuncture versus
the ritual of taking a pill. Those rituals are different.
What's the consequences of those rituals in terms of
people feeling better, in terms of people feeling more
intact, being able to work better. How do those rituals--?
Do those rituals elicit different healing?
In this study, you replicate the experience of acupuncture
without actually giving acupuncture. How do you do that?
TED KAPTCHUK The basic idea is that the needle…It's
a magic sword principle. When you have a magic sword
you stick it in. But instead of the shaft of the sword
going into a person, it goes up the handle, so it retracts.
So basically this is a needle that looks like it goes
in, it feels like it goes in, you see it go in, but
in fact it goes up the shaft. And in fact, the first
time it was done to me I was sure that they had made
a mistake and had given me the real needle.
Okay, don't make any mistake and try it on me. Let me
see here. I actually have a little inflammation in this
finger, so, would you stick me someplace where it would
help that finger?
TED KAPTCHUK Sure. I'll cure it for
ALAN ALDA Thank you. Because… By the way, even
when I know it's a placebo it cures me, so, this'll
TED KAPTCHUK So basically, this is just…. We
do this to both the real needle and the fake needle.
The needle is indistinguishable. It's a real needle.
There's no way you could tell this is not a regular
ALAN ALDA I feel it. Yeah. I felt it.
That's the way a real needle would work, and that's
the way our placebo works.
ALAN ALDA It's also the way
it would happen if the producer was tricking me into
getting a real needle because I don't want any real
needles in my hand. And this is exactly the way it would
TED KAPTCHUK Well, actually we'll have to see.
Make sure it's the placebo needle. We'll pull it out.
Should I pull it out? And that' s it. And then we take
this away and that's it. Now, does it cure your hand?
ALAN ALDA It's only a little worse.
TED KAPTCHUK It's
gonna get much better in five minutes.
ALAN ALDA Okay,
TED KAPTCHUK Let me assure you.
JOE KAY Kathleeen, how much pain would you say you're
in in terms of your right arm? Would you say mild, moderate,
KATHLEEN Um, moderate.
JOE KAY Moderate. How bothersome is the pain?
ALAN ALDA (NARRATION) Joe Kay is one of several licensed
acupuncturists who are lending their services for the
JOE KAY And how much does the pain interfere with your
life? Would you say mildly, moderately, or severely?
ALAN ALDA (NARRATION) He'll be using the discs and tape
- so that the sham needles won't simply fall out - on
all the subjects in the trial.
ALAN ALDA People who come to you as part the study
who have had acupuncture before, are there people like
JOE KAY Yes. Yes, certainly.
ALAN ALDA So when you suddenly put the disk and the
tape on them, do they say, what's this? I've never had
acupuncture like this before.
JOE KAY Many times. But again, with acupuncture, there's
many different styles of acupuncture. It's been around
for a couple thousand years so there's many techniques
that are used. And I just explained to people that this
is one technique that's used to make sure that we get
the exact point.
JOE KAY Okay. That feel okay?
ALAN ALDA Now the patient doesn't know if these are
an actual application of acupuncture needles or a sham
JOE KAY Right. Even if the patient has had an acupuncture
some place else. They really don't have any idea.
ALAN ALDA And neither do I know, if it's real or not.
JOE KAY Right.
ALAN ALDA Now keep going. I want to see if I can guess.
JOE KAY Okay.
ALAN ALDA Would it spoil things for me to say what
I think it is?
JOE KAY No.
ALAN ALDA I think it's the real thing.
JOE KAY Okay.
ALAN ALDA There's something about the way you had to
get it in there. It didn't seem like the fake needle.
JOE KAY You could be right.
ALAN ALDA So let me just get this part of it straight.
This is sort of a placebo effect we're doing here. Kathleen,
you're not really a patient.
KATHLEEN No, I'm not.
ALAN ALDA This is just demonstrating how
the study works. KATHLEEN Right.
ALAN ALDA So--. Do you know what kind of a needle was
going into you?
KATHLEEN Honestly, I thought I'd be able to tell, I
really did. I'm gonna have to ask Joe. I really don't
know what I had. I really don't.
ALAN ALDA What was it, actually? What were you putting
JOE KAY I actually used the placebo needles.
ALAN ALDA The placebo needles.
ALAN ALDA And you couldn't tell--.
KATHLEEN I couldn't. I thought I was getting the real
treatment. I thought Joe was going to tell me later
he really used the needles. I'm surprised. I really
ALAN ALDA (NARRATION) Kathleen wasn't the only subject
to be fooled by the fake procedure.
JOE KAY I had one participant in this study who I was
using the sham needles on, and it was someone who had
RSI for many years. And after about four treatments,
it was completely gone.
ALAN ALDA After four treatments, the person was okay?
JOE KAY After four treatments…they were okay.
ALAN ALDA And had they had any kind of acupuncture
JOE KAY No, they never had acupuncture before.
ALAN ALDA And so they got better from the sham needles.
JOE AKY Right.
ALAN ALDA Wow. How did that make you feel?
JOE KAY Ah, well, from the standpoint of an acupuncturist
it made me feel great because the person was better.
But, on the other end, though, it was like, gee, what
ALAN ALDA I wonder if those twenty years of treating
people has given you a sense of authority in relation
to the patient thats curative in and of itself. You
know, they come in, they get a treatment from you, they
think, "this person clearly knows what he's doing. I'm
gonna get better here." That's not to say that-- That
must be part of doctoring.
JOE KAY Yeah. Ultimately, if that's the case, then
that's fine. If a person gets better then that's what
my goal is.
ALAN ALDA Now, this raises…. I really am interested
to know -- why are you taking part in this project?
Because, what if it's found out, in the course of this
study, it's really not the insertion of a needle in
the right place that does it, that has the positive
effect. It's just the ritual surrounding it, that the
sham needles are just as good as the real needles. What
would that do to your practice?
JOE KAY I don't think it would do much to my practice.
There's a placebo aspect to any sort of medicine. I
mean, even in conventional western medicine as we know
it, there's a placebo effect that's in there. And I
really feel pretty strongly that, you know, once the
data has actually all been crunched, that we'll find
out that the real acupuncture is the real thing. If
it doesn't and I'm proved wrong, I don't think it's
going to necessarily disappoint me or make me change
my profession or whatever.
ALAN ALDA But it might make you change your needles.
I mean, you--.
JOE KAY I won't change my needles.
ALAN ALDA (NARRATION) But remember, the real focus of this
study - which Ted Kaptchuk is still running -- isn't
to find out whether placebo acupuncture is as good as
the real thing. It's to see if the placebo effect is
greater when there's more ritual surrounding a treatment,
as in acupuncture, than when the treatment is nothing
more elaborate than swallowing a pill.
Unless we begin to address those questions, a big part,
a big big part of what medicine's about, gets left behind,
gets put in a trash basket. And one of the things that
it's exciting about the new development in placebo research
is, some things that are in that trash basket is precious,
it's an important ingredient of what makes people healthy.
It's an important ingredient for what makes people feel
better. And we have to bring it on to the table.
ALAN ALDA (NARRATION) In the shadow of the Alps, the city
of Turin has become well known among researchers exploring
the placebo effect. Fabrizio Benedetti and his colleagues
- including Antonella Pollo - have in the last several
years conducted a series of startling experiments here
in the pain clinics of some of the city's largest hospitals.
Today, Luama Collosa is the volunteer subject for one
of these experiments. The Turin group is studying placebo
analgesia - the relief from pain that many people experience
when they believe they're getting a painkiller, but
in fact are not. In this series of experiments, the
Italian researchers will rely not just on Luama's reports
of the pain she experiences, but will also be measuring
her body's reactions.
FABRIZIO BENEDETTI This is for
EKG, electrocardiogram. Electrocardiogram because we
want to see whether or not there is an increase or decrease
in heart rate during the induction of pain, the experimental
ANTONELLA POLLO These two leads are to measure
skin conductance and this is to measure respiratory
rate, it goes up and down with the respiration and it
comes up as a signal on the screen.
ALAN ALDA (NARRATION)
Luama's blood pressure is also being monitored, along
with heart rate, breathing rate and skin conductance
- a measure of how much she's sweating. The pain she'll
experience is induced by inflating a blood pressure
cuff, cutting off the blood supply to her arm and hand.
FABRIZIO BENEDETTI In a scale from zero, which means
no pain to ten, which means unbearable pain, she will
experience around usually after ten minutes, usually
about six, seven.
ALAN ALDA (NARRATION) On this day,
Luama is getting no treatment, either real or placebo.
The goal is to see how her body reacts - to get baseline
measures of its response to the pain in her arm.
ANTONELLA POLLO She said that she experienced on a scale of one
to ten a pain of six.
ALAN ALDA (NARRATION) The next
day, the set-up is the same, except that now she is
receiving an injection for the pain. No one in the room
knows what she's getting.
FABRIZIO BENEDETTI She knows
that she can receive either a placebo or a painkiller.
ALAN ALDA (NARRATION) In previous experiments, the Turin
team has shown that when a placebo injection lowers
the subject's experience of pain, there's an increase
in the brain of natural painkillers, morphine-like chemicals
called endogenous opioids. What's more, giving a drug
that blocks these opioids cancels out the pain relief
caused by placebos.
FABRIZIO BENEDETTI So this means
that there is a close correlation, a tight correlation,
between activation of endogenous opioids and analgesia,
ALAN ALDA (NARRATION) These new experiments
are revealing that the body's response to pain also
changes during placebo analgesia - so the placebo effect
is much more than in the mind. Although the mind must
be where it begins - in the expectations of the patient,
triggered - as all the new research we seen in this
show confirms - by the still mysterious chemistry between
a hopeful patient and a caring doctor.
They should smile, they should talk to their patients,
they should interact a lot with their patients, because
there is a very strong indication that all these mechanisms
- for example the endogenous opioids, the endogenous
painkillers - are released when the patient feels safe,
feels comfortable with the doctor.
TED KAPTCHUK Ultimately
the way a single human being reacts to a single human
being is going to be part of the art of medicine. And
I think we can learn a lot about it from research. Do
I think science will take all the mystery out of healing?
I don't believe so. I think that there's going to be
an element of the shaman residing at the core. My effort
to do research in placebo is to acknowledge that core,
not to destroy that core. 'Cause I don't think it can