– SHOW 1105
are Peppers Hot?
ALDA I'm about to be tickled by a tickling machine.
The question is, will I laugh? Stay tuned.
ALDA (NARRATION) And speaking of laughter -- where does
it come from? We give people colds… RED HAT Definitely
have the cold. The cold, I have it.
ALDA (NARRATION) Then try to cure them. And we ask,
why are peppers hot?
DEWITT Now you said you liked hot peppers.
ALDA Yes I do. I'm Alan Alda. Join me and my laugh box…
as Scientific American Frontiers asks more of Life's
GIRL Why do trees die?
ALDA Why do trees die? That's a really good question.
ALDA (NARRATION) I'm visiting a nursery school…
ALDA Olivia, what's your question?
ALDA (NARRATION) To find out what's puzzling the preschool
Why are buttons round and not square?
ALDA Why are buttons round and not square? That's a
great question. Kids ask the greatest questions. Why
don't all the seas run down to the bottom of the world?
Why doesn't my dog talk? What's that little dangly thing
at the back of my throat? How can Barney be on two TVs
at once? As we get older, we either figure out the answers
or -- more often -- simply stop asking the questions.
That is unless you're a scientist -- and then a lot
of those puzzling little questions we ask when we are
young keep nagging away at your mind. In this show,
we meet some of those scientists who go on worrying
at life's little questions -- often coming up with some
surprising answers. We're starting here, on the campus
of the University of California in San Diego, with just
the sort of question kids love to ask. How come you
can't tickle yourself?
BOY Excuse me. I can tickle myself.
ALDA You can tickle yourself? Let's see. Can you do
HARRIS And if you'll go ahead and have a seat right
ALDA (NARRATION) Despite her being a grown up, Christine
Harris still wonders why we can't tickle ourselves.
And she's devised, I'm told, an ingenious experiment
to help find the answer.
HARRIS If you agree to participate, you'll tickled twice,
once by me and once by my machine. Both times you'll
be tickled on the bottom of your foot. I'm going to
ask you to wear a blindfold and earplugs while we do
this, and the reason for that is so that you can attend
to the sensation of tickle without distraction. So I'm
going to strap your foot in to keep it roughly in the
vicinity of the machine.
ALDA (NARRATION) Now, I have my suspicions that all
is not quite as it seems here. But before I get a chance
to check out the tickling machine any further…
HARRIS Does that feel snug so it's not going to fall
ALDA It could be a little snugger.
HARRIS So the first time I'm going to have my machine
tickle you. So I'll press the button, it will take a
few seconds to initiate, and then it will turn itself
ALDA (Laughs) That was a machine?
HARRIS That was the machine.
ALDA How much does that cost?
HARRIS We'll tell you later. OK, on a scale of zero
to seven, how ticklish would you rate that, with zero
not at all ticklish?
ALDA Well, it must be seven.
HARRIS OK, extremely ticklish. Now this time I'm going
to tickle you, and again I'll ask you to rate it afterwards.
How ticklish would you rate that?
ALDA Only around 5.5 to six. I'm sorry to say. I mean,
you know, you're a nice person…
HARRIS OK, OK, I'm going to go ahead and take off your
blindfold now. And you can go ahead and take out your
earplugs. So did you notice any difference between the
sensation when I was tickling versus when my machine
ALDA Yeah, yeah, I noticed a big difference.
HARRIS In what way?
ALDA The machine was more aggressive. And relentless
-- assuming it was the machine, I was blindfolded, I
couldn't tell. It was as if it was reaching inside my
foot, it wouldn't quit. And the second one was more
HARRIS OK, OK. Would you like to see the machine work
HARRIS So basically I hit that, it takes a couple of
ALDA (Laughs) You know that alone is worth the price
of admission, just to see that. Hello. How are you?
Nice to meet you. Well now, tell me about this machine.
It's a complete fraud, right?
HARRIS Yeah, we call it a mock tickle machine. Mock
sounds better than fraud. And it just is a bunch of
lights and old time sensitivity things that we thought
might look like a real tickle machine.
ALDA Does anyone ever say, that's a tickle machine?
What do you mean, you know?
HARRIS Only one person figured out that it was not a
real tickle machine. What happened is that the research
assistant was under the table and she had her hair up
in a pin and it got caught in the top of the table,
so there was actually this noise as she tried to free
herself from under the table.
ALDA So what did you find out from this test?
HARRIS Well basically what we were looking at is --
no one really knows why you can't tickle yourself, right?
But one hypothesis is that it requires the belief that
it's somebody else doing the tickling. And if that's
the case, and you put someone in here with a machine
and you tickle them with a machine, then they shouldn't
laugh and smile. That's what we were interested in.
ALDA Well it sounds like I completely reversed what
HARRIS No, well actually you I think you fit what I
would expect. That's one hypothesis. And what I think
is, people who believe that tickling is something akin
to a reflex or fixed action pattern, they would suggest
that it shouldn't matter if it's a machine or a human,
that you should laugh and smile regardless of your beliefs.
And so I think this does support that kind of thought.
ALDA (NARRATION) The idea that a machine can tickle
as well as a person certainly goes against most people's
expectations. But in fact most of the subjects actually
experiencing Christine's mock tickle machine were as
tickled as I was -- if perhaps not quite as astonished.
Still, the experiment has what seems to me an obvious
ALDA You haven't really tested for a machine tickling
a person, you've tested only for whether a person believes
a machine is tickling them. If they believe that, will
they have a tickle response? Have you ever had something
like a machine to tickle them with?
HARRIS No we haven't because for us we wanted to test
this assumption that there's something about these beliefs,
and for us this was the right experiment. Because if
you had a tickling machine, a true tickling machine,
and you had it tickling the person, and then you had
a human tickling the person and you got a difference,
maybe the machine didn't cause laughter and smiling
as much, you would never know if it was because the
tactile stimulation was different or if it was the belief
in the machine. So for us it was the right experiment.
But we haven't actually built a real machine.
ALDA Actually it's probably extremely difficult to build
a tickling machine.
ALDA (NARRATION) Difficult -- but not, it turns out,
impossible. In London, psychologist Sarah Blakemore
recently built a robot that would tickle people's palms.
It doesn't look as much fun as Christine's mock machine,
but like hers it did succeed in being tickly.
BLAKEMORE So could you tell me how that stimulus felt,
on a scale from zero meaning not at all to ten meaning
ALDA (NARRATION) What was clever about this experiment
was that subjects could also control the robot themselves.
And when they did, it stopped feeling tickly -- unless
the robot had a built in delay, when the tickling sensation
returned. So you can tickle yourself -- but only indirectly.
SARAH BLAKEMORE So you can feel the tactile stimulus
on your hand now…
ALDA (NARRATION) Sarah Blakemore then put volunteers
into a scanning machine to see if there was any difference
in how the brain responds to self-tickling as compared
to machine tickling. The experiment suggests that the
brain has a self-censor, a damping signal sent from
the region monitoring movement to the region reacting
to touch -- a useful survival mechanism making sure
we don't jump in surprise every time we touch our own
bodies. So that's why we can't tickle ourselves -- our
brains won't let us. But there's another little question
about tickling. How come it makes us laugh? Is it because
we find it funny -- funny in the same sense we find
humor funny? No less an authority that Charles Darwin
suggested a link between ticklish laughter and humorous
laughter -- so Christine Harris set up another experiment.
We will work with the customer to give that customer
the change he or she needs.
ALDA (NARRATION) Her idea was to exploit what comics
call the warm-up effect: it takes a joke or two to get
the audience in the right mood.
If you come to us with a hundred dollar bill, we're
not going to give you two thousand nickels, unless that
meets your particular change needs.
ALDA (NARRATION) If ticklish laughter and humorous laughter
are the same, then warming someone up with a funny video
should also make them more ticklish.
We will give you the change equal to the amount of money
you want change for.
ALDA So at what point do you tickle her?
HARRIS So after she's watched the video, and laughed
and smiled at the video, then we'll do the tickling
and so Noriko… We're going to tickle you anywhere from
the underarms to the waist, and so if you just loosen
your arms, you can lean back but just let your arms
fall kind of loose. OK?
ALDA (NARRATION) Margaret certainly didn't seem very
I'd say that was about a two.
ALDA First of all, do you find that people are warmed
up by watching the video?
HARRIS No. Actually we didn't find an effect of warm
up. So if you've just watched a nature film or if you've
just watched a comedy it doesn't affect how much you
laugh or smile in response to tickling. And vice versa,
if you are tickled and then watch a funny film it doesn't
increase the amount of laughter.
ALDA Did it seemed similar to you to the laughter you
had when you were laughing at the tape?
Not at all. No, it didn't seem humorous to me. I mean
the squirmy feeling is the reaction, but it wasn't the
same sensation evoked by the video.
ALDA (NARRATION) Which brings us to the biggest little
tickle question of all -- just why are we ticklish?
Christine Harris thinks it might help develop combat
I got you. Adam, I got you. You can't get away!
ALDA (NARRATION) The laughter keeps the tickler tickling
even while the tickled is trying to escape.
HARRIS It looks like you're having the time of your
life, you look like you're loving it, you're laughing
and smiling, but a lot of people don't actually like
to be tickled.
ALDA Do you?
HARRIS No, I don't. I don't, no.
ALDA (Laughs) You don't seem to like to talk about it…
PROVINE OK, we've got another experiment for you. This
has to do with the little boxes on your desk. Ready?
OK, push the button.
ALDA (NARRATION) All that tickling got us thinking about
laughing. So we dropped in on Bob Provine's class at
the University of Maryland with another of our deceptively
simple little questions: just what is laughter?
PROVINE OK, well I think it's undeniable that laughter
is a really powerful sound. You didn't decide to laugh,
you just laughed when you heard the laughter. There's
something special about that sound.
ALDA (NARRATION) Laughing just happens to be one of
my favorite activities -- so I'm more than happy to
provide a laugh for Bob's computer.
PROVINE You notice how much more regular that was than
speech. So as I speak in to the computer here, we see
that there's a very irregular pattern as opposed to
those regular hills and valleys that were separated
by regular intervals when we laughed. For example… (laughs).
ALDA (NARRATION) Bob Provine, as you've probably guessed
by now, is a laughter expert.
ALDA Have you seen anybody about that?
PROVINE Ahhh, there's no known treatment for it.
ALDA (NARRATION) He's listened to laughter from cultures
around the world and always finds this characteristic
pattern of regular peaks and valleys.
PROVINE And in fact it's very difficult to laugh in
other than that regular way. For example, could you
laugh really fast.
ALDA Laugh really fast.
PROVINE A high speed laugh. (Laugh)
PROVINE OK, we still have the peaks and valleys.
PROVINE But that's not much faster than what we were
doing. Try to laugh faster.
ALDA (Laugh) A little sinister there.
PROVINE Try one more.
PROVINE I'm not too proud to do this, so you don't be.
ALDA (NARRATION) Provine argues that not only is human
laughter highly stereotyped -- it also sets us apart
from all other animals.
PROVINE The chimpanzee laughter is like this: aha, aha,
aha, aha. And if in fact you were tickling a chimpanzee
and rolling around in a little rough and tumble play
with a chimpanzee, which is what we've done as part
of our research, that chimpanzee will perform what's
called a play face and make that sound. And you would
be absolutely convinced that that is laughter, even
though the sound's a bit different. But the sound is
not just different; it's different in a way that makes
a huge difference. It's a difference that reveals to
us why we can talk and chimpanzees can't. You know,
when I laugh, I'm going ha, ha, ha -- I'm chopping an
outward breath. Well, chimps don't do that -- can't
ALDA And why?
PROVINE Chimps laugh by going aha, aha, aha. Their laughter
is locked in to their cycle of breathing.
ALDA So it's both in and out.
PROVINE Yeah, it's in and out.
ALDA And they can't chop off an expulsion of air, they
can't take an exhalation and chop it into discrete bits.
PROVINE Yeah, that's exactly…
ALDA The way we can. What is there about us that enables
us to do that?
PROVINE Well. I was puzzling about this for a long time.
And our most recent work has indicated that it's being
able to stand up and walk on two legs.
ALDA (NARRATION) When a four-legged animal walks or
runs, its breathing is literally locked in step with
its stride. Only humans, Provine argues, whose forelimbs
no longer support weight, can breathe freely.
ALDA So the ability to stand up, however that derives,
also conferred on us the freedom for our lungs to now
be directed, used in other ways. I mean, was that automatic?
Do you suppose that people automatically started laughing?
Ho, ho, look at this, ho, ho. I mean, how do you get
from being able to stand up, do you suppose, to actually
producing these staccato sounds?
PROVINE Being able to walks upright on two legs is the
necessary event but not sufficient. So when you walk
upright on two legs this means there can be selection
for the fancy sound making we call speech.
ALDA (NARRATION) So according to Provine, the regular
sounds of laughter allowed our ancestors gradually to
evolve the irregular patterns of speech. A nice idea.
But what's laughter for today?
PROVINE Laughter is really not about jokes, it's not
really about comedy…
ALDA Now you tell me!
PROVINE It's about relationships between people.
ALDA (NARRATION) Laughter, he argues, is a sort of social
lubricant, occurring thirty times more often when people
are in groups than when they're alone…
GIRLS We always laugh together.
ALDA (NARRATION) … and often for no obvious reason.
PROVINE Laughter is an unconscious response, and we
don't have complete control of it. Good actors can simulate
a laugh. But like you can't cry on command, most people
can't laugh on command and it's very apparent when they
MAN Laugh? (Fake laughter) Oh my god, that was funny!
PROVINE In fact, if you ask a person to laugh, their
first response will be well. I can't laugh on command,
I can't just laugh because you ask me to.
Just make yourself laugh, huh?
I guess I can't do it.
MAN Laugh? I've got to think of something funny now.
CANADIAN Well, you see, we're Canadian…
CANADIAN Yeah, we're Canadian, we're not able to spontaneously
laugh like that. You know, quiet, reserved…
PROVINE And of course, after that they may laugh, ha,
ALDA They're laughing then not because you asked them
to, they're laughing because of some social glue they're
hoping to exude.
ALDA (NARRATION) And then there's another kind of laughter
-- the nervous giggle that can inflate to the verge
Someone make a joke or something…
ALDA I saw somebody laugh for half an hour because we
were right next to the cliff. And it was ha ha, ha ha
-- what's the matter -- nothing, I'm fine. Or seeing
a snake, you know, I see a snake, there's a snake --
are you OK -- no, I'm fine, it's just a snake, I'm OK.
Now that sound like it's taking us back a good 200,000
years, or a million years, to somebody who's upright
PROVINE I think we overestimate how reasonable we are,
and in laughter we're penetrating beneath that veneer
of civility and language and rationality into something
that's very primitive, very deep and we share with other
animals. So just as we go to the zoo and hear other
animals make various calls and cries, when we examine
our own laughter it's exactly those kinds of sounds.
ALDA The questions pop into our heads every time it
happens. Along with the unexpected sneeze or the suddenly
scratchy throat, we wonder, how did I catch it this
time? How bad is it going to be? Should I take some
vitamin C, suck a lozenge, drink some herbal tea? And
then there's the big one. If scientists can send a man
to the moon or invent the Internet or peer at distant
galaxies, why can't they cure the common cold? Well,
I've come here to Charleston, South Carolina, to find
out. Because Charleston is about to experience a sudden
mini-epidemic, an outbreak of runny noses and stuffy
heads that could take us one step closer to an answer.
ALDA (NARRATION) What's unusual about this outbreak
of colds is that it didn't just happen.
Put it in the cup. In the cup. In the cup.
(NARRATION) These volunteers, whose noses are being
rinsed out with a saline solution, are being paid to
catch a cold.
ALDA If you wash his nostrils out he'll have a better
chance of catching cold?
WRIGHT Mm, mm. 'Cos the nose'll be nice and clean.
ALDA 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
ALDA (NARRATION) The man dispensing the colds is Ronald
Turner, an old hand at conducting studies on candidates
for cures. What he's carefully placing up the nostrils
of his volunteer subjects is a strain of rhinovirus,
one of the commonest causes of the common cold.
ALDA Now you already had one of these?
SANDERS I had one. I had one already.
ALDA So how many do you give?
TURNER Two. We just go around twice.
ALDA You really want to make sure you make these poor
TURNER OK, this is the same as before.
ALDA (NARRATION) Actually, Ron Turner is hoping some
of his volunteers won't get sick…
TURNER Here we go again.
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.
TURNER Some are getting active medication, some are
getting placebo. Everybody gets the virus.
ALDA Now do you know, are you aware of who's getting
the placebo and who's getting the medication?
TURNER No, we're all blinded.
ALDA You don't have any idea?
SCIBELLI This is what they look like.
ALDA The famous ju-ju bead medication. So what do you
think is in there?
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.
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.
Do you think you were getting the active medication
or the inactive medication?
SANDERS I think I was getting the inactive.
BOZARD I have no idea. I really don't. I had no side
effects, no symptoms of any kind either way, so…
OK, give me a guess.
MIN I think I was getting inactive.
GORDAN I don't know. It was just that whenever I took
it I felt, like, fuller.
LEWIS I have no idea. I'll have to say the active medication.
Why would you say that?
LEWIS It'd kind of depress me if I was having the other
DUGAN I would say the inactive.
Why would you say that?
DUGAN Just because I didn't feel any difference.
ALDA Do you think it matters whether or not you believe
you're taking the active ingredient?
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
ALDA (NARRATION) Lindsey's right: if people are able
to figure out what they're getting, then it could dramatically
influence the results of the trial.
SCIBELLI I'll go with active.
Why do you say that?
SCIBELLI I'm hopeful.
ALDA (NARRATION) In fact, in Ron Turner's opinion, many
of the clinical trials of popular cold remedies are
fatally flawed by this very problem. His list includes
even that old stand-by vitamin C -- and, distressingly,
two of my personal favorites, zinc lozenges and echinacea.
He's tested both in carefully controlled trials like
his current one, and found they don't work.
ALDA All right. I've got one left. If you kill this,
I'm never going to be able to fight off a cold again.
TURNER Well, vitamin E is interesting, and we've looked
at vitamin E as well. There's some biologic rationale
for vitamin E, and for vitamin C for that matter, in
the sense that they are both anti-oxidants, and we do
think that oxidative stress in the cell has something
to so with production of the symptoms of the cold. And
so we did a study of vitamin E, where we gave vitamin
E supplements for a couple of weeks to a group of volunteers.
We drew blood from 'em, we showed that the vitamin E
levels in their blood were substantially higher than
in the placebo group, and then we challenged them in
our model with our virus and had absolutely no effect.
ALDA So it was no good as a prophylactic, but…
TURNER Or as a treatment.
ALDA Or as a treatment either?
ALDA I'm dead. That's it. I've got nothing left.
TURNER Well the good news is that you'll get over your
SWAIN Definitely have the cold. The cold, I have it.
LEWIS I don't feel ill at all. If I'm supposed to be
ill right now, I'm not ill.
I have the cold.
ALDA (NARRATION) Three days have passed since our volunteers
were infected with the cold virus. They've been reporting
in every morning since.
It's been about 72 hours since the inoculation. Do you
think you received a cold?
SCIBELLI Yeah, I do. I definitely had it yesterday.
OK, I want you to rate your symptoms this morning, based
on the severity since your last visit. Any symptoms
SCIBELLI I'd say about a two.
OK. Runny nose?
Nasal stuffiness or obstruction?
ALDA (NARRATION) There are a dozen symptoms on the list
-- enough to get a pretty objective measure of the severity
of the cold.
Definitely getting a little bit worse, huh?
OK, you can go on back and get your nasal wash.
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.
SANDERS I think I'm receiving just a placebo. (P)
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. (P)
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. (P)
HOEFT Based on how mild my symptoms are, I think maybe
I did get the active. (A)
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. (P)
MIELCAREK I think I got the inactive medication because
I've been getting worse as the days go on. (A)
DUGAN I guess I got the active medication, 'cos all
I've had is a runny nose and that's it. (A)
ALDA (NARRATION) Perhaps not surprisingly, 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 didn't.
That's right, the mystery herbal ingredient in those
big brown pills did nothing in Ron Turner's study --
joining on his hit list echinacea, zinc lozenges and
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?
TURNER 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…
ALDA That's the best you can come up with? After all
TURNER Well, I think we're doing better than that. I
think we're doing better than that.
ALDA (NARRATION) One way in which science may at last
be doing better is in attacking cold viruses themselves.
A big reason the common cold hasn't been cured in the
past is that so many different viruses can cause it.
WORLAND And for many, many years, people thought that
was going to make it impossible to develop therapy for
the common cold.
ALDA Yeah, that's what I've read, constantly, that there's
too many colds, too many viruses, to be able to find
something common in all of them.
WORLAND Right. And I remember when I first started on
this project, somebody who I was good friends with in
college who -- we diverged slightly, he went into medicine
and I went into basic biochemistry -- I told him I was
working on this and he laughed his head off. He said,
there are over a hundred serotypes, no one will ever
ALDA Now your friend is giving out anti-histamines and
you're solving the common cold!
ALDA (NARRATION) Steve Worland's company, Agouron, is
trying to attack the commonest group of cold viruses,
the rhinoviruses. Their target is actually a protein
called protease, that all rhinoviruses use to make copies
of themselves. The company started by making tiny crystals
of this crucial protease, then used an X-ray crystallography
machine to get a precise three- dimensional picture
The X-rays are generated right here, and if you stand
up you can see the tip of the loop, the crystal is very
small, only a couple of tenths of a millimeter. What
we're seeing here is an electronic image…
ALDA (NARRATION) Now, there are moments, when we're
making Frontiers, when we get just a little out of our
ALDA What do you do, roughly, to get a three-dimensional
picture from these dots?
Well, basically what we do, we use computers to carry
out a three-dimensional Fourier summation, and the individual
coefficients in that Fourier series are related to the
intensities we're measuring here.
ALDA And that's the rough version.
ALDA (NARRATION) OK, well once they did that, this was
the result, a 3-D image of the protease the virus needs
in order to replicate itself in our nose cells.
WORLAND That was enough to say that there are regions
where the protein goes in rather than comes out where
we can plug in, if you will, our drug molecule.
ALDA The reason you want to plug your drug molecule
in is that if you don't do that, this is going to be
a place where the protease is going to hook up with
what it needs to it hook up with to do its work and
help the virus to replicate.
WORLAND That's precisely right.
ALDA (NARRATION) The drug molecule Agouron designed,
which nestles neatly into the critical protein, successfully
stopped the virus from replicating in a test tube. The
next step was to try it in noses.
Good morning everybody.
ALDA (NARRATION) In a clinical trial very similar to
the one Ron Turner ran, the anti-viral drug was tested
on college students at the University of Virginia --
except that here the subjects got to stay in a hotel.
Twenty-four hours after getting infected, they received
several daily doses of the experimental drug in a nasal
spray. Here too, some of the subjects got a placebo
spray instead of the real thing.
Do you feel generally bad?
I feel like I've got a cold.
OK. That's what I need to know.
ALDA (NARRATION) The severity of their colds was judged
by questionnaire, by measuring the virus directly, and
by weighing the tissues they used. And the results were
promising -- a significant reduction in cold symptoms
among those on the drug.
How you feeling this morning?
I'm doing fine.
No cough, no sore throat, no nothing?
All right. That sounds good.
ALDA (NARRATION) Even though the drug seems to work,
getting it to market will be far from easy. It will
have to be cheap; it will have to work fast; and, as
Steve Worland knows only too well, it will have to be
WORLAND It's a real drag to have a cold, but it's not
life threatening. And so in that case we're even more
concerned about a safety burden because we're not treating
something like cancer or HIV where a certain degree
of side effects traded for saving somebody's life, that
person would almost always say, I'll take it.
ALDA It's not worth trading a serious side effect to
get rid of a cold.
WORLAND Exactly. So this really has to be a compound
with virtually no side effects or people are just going
to elect not to take it. If you tell people, well, you
know, you're going to feel numbness in your hands, just
as a hypothetical example, but your cold will go away,
most people will say, I'll take the cold.
ARE PEPPERS HOT?
ALDA (NARRATION) Our next little question brings us
to Santa Fe, New Mexico, and a food festival celebrating
what's practically the state food - the chile pepper.
The question is of great personal interest to me. But
it isn't one you'd imagine leading to a medical breakthrough.
ALDA So here's the question: Why are peppers hot? Well,
why are they hot?
BOSLAND Chiles are hot because they have a compound,
or a set of compounds, called capsaicinoids that's found
inside the fruit, along the placenta. And contrary to
a lot of beliefs, the walls have no heat, the seeds
don't have any heat, they're only in this one little
area here - where this orange coloring is? - that is
the capsaicinoids. So the more orange, the hotter the
ALDA (NARRATION) My hosts' plan is for me to sample
some of the different peppers here so that I can appreciate
their subtleties. But for me subtlety and peppers don't
mix. So offered a choice of mild, medium or hot…
ALDA Let's get hot right away.
DEWITT OK, this is the Capsicum picatum, I'll let you
try this. Also know as aji in South America.
ALDA It's good.
DEWITT Now you said you liked hot peppers.
ALDA Yes I do.
ALDA (NARRATION) I'm not the only one here playing with
fire. Paul and Dave are still determined to teach me
the fine art of pepper tasting. But I get the horrible
feeling it's already too late.
BOSLAND The three areas to look for is the front of
the mouth, mid mouth and the back of the throat, the
ALDA Tastes like oatmeal. I don't taste anything.
DEWITT Oh, we burned your taste buds with the hot one…
BOSLAND Well let's try this one. We'll see what happens
here. It's a little hotter now.
ALDA OK…Tomato sauce.
DEWITT We burned you out, that's what the problem is.
It may be several hours before your palate gets back
ALDA Why are we in red light like this?
ALDA (NARRATION) Burned out my palate? This sounds serious
-- which is why I find myself sitting in a very strange
room in Baltimore.
ALDA This is very futuristic.
KING Yes it is.
ALDA Oh look, there are little screens down there.
ALDA (NARRATION) I've come here to check my heat-sensing
abilities against some of the best-trained tongues in
the world, belonging to the members of the pepper-tasting
panel at one of the nation's largest spice companies,
McCormicks. Sylvia King is in charge.
KING Everybody get set, and go.
ALDA (NARRATION) We start with what's reckoned to be
a mild solution of the hot pepper chemical capsaicin.
ALDA (NARRATION) We're instructed to assign it a five
on a heat scale of zero to fifteen.
KING So is everybody ready? Rinse with water and rinse
with a cracker.
ALDA (NARRATION) A cracker, hmm? What happened to the
ALDA Does the cracker really clear out the sensation
KING It will help. Get ready for your strong reference.
ALDA (NARRATION) The idea here is to tune our tongues
to a standard set of heats -- concluding with a dose
of capsaicin scoring a respectable 13 on the heat scale.
ALDA (NARRATION) OK, with our tongues now calibrated,
it's time to see how we all rate a sample from a real
hot pepper -- which is why, by the way, the light's
red -- to disguise the sample's color, so it won't influence
KING Set and go.
ALDA (NARRATION) I'll give it an 8. And my fellow tongues?
GILLETTE I would give it about a 7.9
TASTERS 7.5…about a 7…7.2…about a 7.6…
ALDA (NARRATION) Well that's a relief. My tongue seems
right in line with the experts'.
TASTERS 7.5…7.8…7…about an 8.2.
ALDA I'm sort of amazed that I even could taste anything
in the mild one, you know. I was really afraid when
I came in here you'd say this is the mild one and I'd
say, no that's water!
ALDA (NARRATION) Of course, the spice company didn't
set up the heat-sensing panel just for my peace of mind.
It's one of several ways they check the heat of all
the peppers they buy, so that their customers don't
get a nasty surprise once the pepper's ground into powder
or flakes. Still, heartened that my tongue has survived
years of hot pepper pummeling, I took it to a specialist.
ALDA So if I can taste this as extremely bitter I'm
BARTOSHUK A supertaster.
ALDA I'm a supertaster. If I can't taste anything…if
it tastes like a piece of paper…
BARTOSHUK You're a non-taster.
ALDA Oh boy.
BARTOSHUK And if it's something in the middle, you're
a medium taster. Be sure the paper gets really moistened
with your saliva and moves all around so it covers your
whole tongue. Are you tasting anything?
ALDA It's bitter.
BARTOSHUK Ah yes, yes. Authentic supertaster.
ALDA It's really bitter.
BARTOSHUK Oh oh, alright, I think now's the time to
take it out.
ALDA If I'm not a supertaster, I don't want to know.
This is close enough.
ALDA (NARRATION) Only one person in four is a supertaster…
BARTOSHUK I can't share that experience with you because
I'm a non-taster.
ALDA (NARRATION) While another one in four, like Linda,
doesn't taste the paper at all. The paper was only the
beginning of my tongue check-up - next came blue food
BARTOSHUK OK, swallow. Move your tongue in your mouth
a couple of times and swallow a couple times, and that
will distribute the dye. And then we'll have a look.
Stick your tongue out. Oh, magnificent, the staining
is absolutely perfect, I can see the pink fungiform
papillae. Your tongue looks like it's tiled in fungiform
papillae. You definitely look like a supertaster.
ALDA I'm a supertaster.
ALDA (NARRATION) The fungiform papillae are little sprouts
on my tongue. Each one harbors a half-dozen or so taste
buds, with nerve fibers connecting them to my brain.
While some of these fibers convey the sense of taste,
most of them don't sense taste at all, but pain. Which
brings us back to hot peppers.
BARTOSHUK You are feeling way more pain from eating
a red pepper than I would, for example.
ALDA Because I have more of these structures.
BARTOSHUK That's right. You have way more pain fibers
so you perceive way more pain.
ALDA This is really weird because I eat far more red
pepper on my food than anybody I know.
ALDA (NARRATION) Now of course it may be that I just
like pain more than most people. But there's another
explanation, which goes back to that hot pepper I ate
in Santa Fe. Because it not only knocked out my sense
of taste. After the initial burn, it actually numbed
the pain fibers that nestle around my taste buds.
ALDA Now that this is cooled a little I put the pepper
ALDA (NARRATION) Which is why I'm helping make hot pepper
candy. A dash of cayenne pepper before the traditional
ALDA Both thumbs, I have both thumbs in the taffy. I
can't get my thumbs out of the taffy.
ALDA (NARRATION) And the result is a candy that Linda
Bartoshuk uses to treat patients with painful mouth
sores. The candy was the idea of a student of hers,
but others had thought of it before.
BARTOSHUK If you go back and read accounts of Aztec
medicine, you'll find out that the Aztecs were using
chile peppers mixed with honey to treat sores in the
mouth. My guess is that every culture that has ever
consumed these chile peppers has figured out that they
are really good analgesics. We're just the last in a
long line of people who've looked at that.
ALDA (NARRATION) One man who's that happy researchers
are again exploring the pain-killing properties of peppers
is a long-term survivor of AIDS, living in San Francisco.
A few years ago, he began suffering agonizing pain in
his feet due to a condition known as neuropathy.
The pain was very, very deep inside my feet, just underneath
the toes. The best way I can describe it was that there
was broken glass in there, on the nerves, to the point
my life was just becoming very sedentary.
ALDA (NARRATION) An active runner and volunteer with
the AIDS quilt project, Geppetto Apodaca became housebound,
his pain controllable only with powerful drugs.
I thought that if this pain continues, and if all they
can do for me is tranquilizers, then I just didn't want
to go on any further. And that's pretty much where I
was until I met the pain management crew and Wendye
ROBBINS An interesting day to be doing this from a symbolic
perspective. This is the start of the Jewish calendar.
ALDA (NARRATION) Wendye Robbins, an anesthesiologist,
figured if hot peppers numb pain in the mouth, why not
ROBBINS That was part of the originality of the invention,
was realizing that the same nerve fibers that are present
in the mouth and signal hot or spice when we eat them
are also present on the foot and therefore can probably
be interacted with in the same way.
ALDA (NARRATION) Geppetto's treatment begins with a
powerful local anesthetic smeared on his feet.
ROBBINS Before we put capsaicin on him we have to make
sure he's pretty numb. Otherwise the capsaicin itself
would be exquisitely painful.
ALDA (NARRATION) The mask protects against the fumes
from the capsaicin cream.
ROBBINS This is a hundred fold more potent than the
stuff that's available commercially. This is 7.5% by
weight. If I was to touch this to your foot, or to the
foot of anyone else who wasn't anesthetized, it would
be excruciatingly painful.
ALDA (NARRATION) While we wait for Geppetto's feet to
bake, we've time for a quick visit with another team
of San Francisco scientists. With research materials
bought from local supermarkets, their goal was to find
the molecule in our bodies that responds to peppers'
heat. Among the peppers David Julius and Michael Caterina
tested was the habanero, the hottest of all.
JULIUS Very pungent. Tearing my eyes. Making it a little
hard to breathe. All for science, you know.
ALDA (NARRATION) What the researchers have found is
the molecule in our nerves that hot peppers activate
when they cause their painful burn. The molecule sits
like a trapdoor on the surface of the pain fiber. Capsaicin
unlatches the door, allowing calcium ions to rush in
-- and so firing off the pain message to the brain.
Here's what happens when capsaicin is added to living
cells that are cued to light up when the trapdoor opens.
CATERINA If you were to take the neurons that normally
respond to pain in our bodies and and subject them to
this same sort of assay, this is exactly what they would
look like. They would start off purple and then when
you added capsaicin to them, they would all light up.
A silent scream.
ALDA (NARRATION) The researchers discovered that very
hot water also makes cells give this same response.
In fact, the original job of the trapdoor molecule in
our bodies may have been to detect and warn of dangerous
heat. So here's the ultimate reason peppers are hot
- capsaicin fools our cells into thinking they're on
fire! Right now Geppetto's feet know the feeling only
I'm beginning to feel a very, very, very hot sensation
on my feet right now.
ALDA (NARRATION) But just as the hot pepper candy relieves
mouth sores, so Geppetto's much more dramatic treatment
should relieve his much more devastating pain - once
the burn wears off.
The first time we did it, my initial feeling when I
got home was that the pain was so bad from the capsaicin
that I couldn't realize that it was going to get any
better. And as the third day came around and I was able
to put on shoes comfortably for the first time, it was
like being born again.
ALDA (NARRATION) This time Geppetto was running again
within the week - and if his previous treatments are
a guide, he'll remain virtually pain-free for months.
Meanwhile, Wendye Robbins hopes that many other patients
with debilitating pain can also be treated with pepper's
ALDA The beach is a great place for thinking up trivial
questions. For instance, have you ever noticed that
when you walk in wet sand, the color of the sand seems
to change in a sort of halo around each footstep? Why
is that? It's no coincidence that this particular little
question popped up here, on the shore of Lake Michigan
in Chicago, because at the University of Chicago are
a couple of scientists who just love asking trivial
questions about stuff like… well, stuff like sand. You
really do love sand, eh?
NAGEL Of course, it's one of the best substances there
ALDA What about my question. Why do we get this sort
of halo around our footsteps when you walk on wet sand?
NAGEL What we've got here is sand in this squeeze bottle.
And we've filled it with water to a little bit higher
than the level of sand. And so, as I squeeze this, what's
going to happen? Normally you would think that everything
is just going to rise. But as you saw with the sand
near the lake, you squeeze it and the water drops below
the level of the sand.
ALDA That's great. You let go of it and the sand goes
down and you have a layer of water on top. You squeeze
it - look at that water, it seems to go all the way
down there and the sand goes right up
ALDA (Narration) The explanation's actually simple.
Squeezing the bottle makes the sand grains move past
each other -- and to do that, they must first move slightly
apart. The water then runs down into the bigger spaces
between them. On the beach, my weight pushed the sand
grains apart, and the water draining away created the
haloes. In fact, whenever grains move, they must first
move away from each other. For instance, only the seeds
on the surface of this avalanche have the room to expand
and so to flow. And it's when sand flows that it really
ALDA What is this orange thing?
NAGEL This is a puzzle, which has orange sand in this
plastic tube, and in the middle of the sand we have
this big steel ball. And the question I have for you
is, the ball is on one side and I want you to get the
ball over to the other side of the container.
ALDA OK, so the ball is on this side, I have to get
the ball to this side of the sand, eh?
NAGEL That's the idea.
ALDA OK, so the first thing obviously is to try to shake
ALDA (Narration) Obvious perhaps -- but equally obviously,
not effective. Stubbornly, the ball refuses to sink.
NAGEL Suppose you try it upside down?
ALDA It's climbing right up! There it is, there it is,
it's right at the top. OK, what makes it climb up through
the and like that?
JAEGER Great question. And to answer that, we're going
to the lab.
ALDA (Narration) The lab we're heading for is the University
of Chicago's Materials Center.
NAGEL So this is the two dimensional version in a real
laboratory situation of what you saw here.
JAEGER Let's just turn this thing on.
ALDA Look at that, wow! And there it goes, down the
side. I was just going to say, I can see poppy seeds
moving down here.
NAGEL But this big one can't make it, can it?
ALDA (Narration) The only thing going on here is that
the container is being briskly shaken up and down. It's
a fancy version of what can sometimes happen if you
shake a can of mixed nuts. The shaking un-mixes them,
causing the large nuts to rise to the top. Remarkably,
there's never been a good explanation for this phenomenon.
But a clue came from that thin downward stream of grains
I'd noticed along the wall. Here's what Sid and Heinrich
think is happening. As the grains are thrown upward,
those nearest the wall are dragged against it, slowing
them down. When the grains fall, they're less densely
packed, so there is less drag against the walls. The
result: the grains next to the wall slowly move downward,
setting up a sort of convection current. The current
rises in the center, carrying everything with it. But
at the walls the current is too narrow to take large
objects down again, so they are left stranded at the
top. In a shaken can of mixed nuts, the Brazil nuts
present themselves ready for eating. All very interesting,
ALDA Suppose mixed nuts is not the most important thing
in your life. What else does this apply to, anything?
Or is it great that we have this understanding of how
NAGEL Mixing is a terribly important thing in the pharmaceutical
industry. That is, if you are making pills out of various
powders, you want to mix them. And if you don't mix
them properly, then you'll have some pills that have
all the binder and other pills that have all the good
stuff, but having all the good stuff in one pill is
very, very bad.
ALDA You could kill somebody.
NAGEL You could kill somebody with that.
ALDA (Narration) A great example of how an apparently
trivial question can lead to a very non-trivial answer.
One of Sid Nagel's favorite little questions confronted
him one day from his kitchen counter.
ALDA Are these historic coffee stains here? Are these
the ones that gave you your inspiration?
NAGEL Oh, they're a day old or so. But when they're
as lovely as this, wouldn't you have trouble wiping
ALDA (Narration) Yes, it's true, Sid really does find
coffee stains beautiful -- because they made him wonder
why, when a coffee spill dries, it always leaves a ring.
Enough of Sid's colleagues took the question seriously
that experiments began to watch what happens as a coffee
NAGEL So Rob here has been looking under a microscope
at some of the drops that instead of using coffee we've
used particles that you can visualize under microscopes.
ALDA I'm seeing a lot of particles moving from over
here to the edge.
ALDA (Narration) The question was, what's causing this
flow? The answer hinged on the fact that the edge of
a spill becomes pinned in place by tiny rough spots
on the surface, so the edge can't pull back as the liquid
evaporates. As the edge loses liquid to the air, it
has to be replenished by liquid from within the drop
- and the flow that results carries with it the tiny
ALDA Is this white band particles that have built up
on the edge already?
NAGEL That's right. And so you see how slowly and carefully
they come in there and they pack very nicely into a
very well packed, almost crystalline ring.
ALDA (Narration) The careful packing means that even
this humble discovery could have unexpectedly useful
consequences - for instance in manufacturing ultra-fine
wires in electronic circuits. So even in coffee stains,
there can be inspiration.
ALDA It's really interesting to me that this kind of
stain from a few drops of coffee has probably shown
up on countless millions, thousands of millions, of
NAGEL On my counter top alone it's shown up that many
ALDA And many of these counter tops were the counter
tops of serious, curious scientists. And yet you and
the people you work with took these stains seriously
and you thought that something can be learned from that
that will lead us to a deeper understanding of things
other than coffee stains
NAGEL I have this kind of broad view of what physics
should be. And it's not just building the big new superconducting
supercollider or a new Big Bang theory of the universe.
It's also trying to understand phenomena such as this
that gives us the feel and texture of our daily lives,
and it's just important to understand.
ALDA It's possible then that by studying things like
coffee stains on the counter top and sand in an hourglass
or nuts in a container of mixed nuts really can give
you some insight into how the whole universe is formed.
ALDA (Narration) See where wondering even about the
little things can take you…?