Speaker 1: Welcome to Stuff to Blow Your Mind production of iHeartRadio.
Speaker 2: Hey, welcome to use Stuff to Blow your Mind. My
Speaker 2: name is Robert.
Speaker 3: Lamb and I am Joe McCormick, and we're back with
Speaker 3: part two in our series talking about the winners of
Speaker 3: the twenty twenty four ig Nobel Prizes. The Ignobels are
Speaker 3: awards given out each year by a scientific humor magazine
Speaker 3: called The Annals of Improbable Research to both satirize and
Speaker 3: honor scientific achievements that are likely to strike people as
Speaker 3: funny for one reason or another. We cover the winners
Speaker 3: most years, and this year is no exception. So on
Speaker 3: Tuesday in part one of this series, which, by the way,
Speaker 3: if you haven't listened yet, maybe go check that one
Speaker 3: out first. But in Tuesday's episode, we talked about the
Speaker 3: twenty twenty four Physiology Prize winner, which was a study
Speaker 3: on using the a to deliver supplemental oxygen to pigs, mice,
Speaker 3: and potentially one day, human beings. And we also talked
Speaker 3: about a classic experiment from the history of dairy science,
Speaker 3: which involved trying to stack cats on top of cows
Speaker 3: and get them all freaked out with exploding paper bags
Speaker 3: in order to understand something about milk production.
Speaker 2: Yeah, and you know, if you were, if you're impatient
Speaker 2: and you're like, just give me the full list. Don't
Speaker 2: want the fullest of winners from this year and every
Speaker 2: other year that there's been an ig Nobel Prize. You
Speaker 2: can go to Improbable dot com. That is, that's the
Speaker 2: official website, and it's all all laid out for you
Speaker 2: in a very handy format.
Speaker 3: That's right, And we're not going to be talking about
Speaker 3: all of this year's winners. We most years we don't
Speaker 3: talk about all the winners. We're just we read through
Speaker 3: them and pick out some that are especially interesting to
Speaker 3: us and focus on those to try to get into
Speaker 3: more depth.
Speaker 2: Yeah.
Speaker 3: All right, So to kick things off today, I'm going
Speaker 3: to start by talking about the twenty twenty four prize
Speaker 3: in the arena of Medicine. And this selection is one
Speaker 3: of those where the nature of the experiment is funny,
Speaker 3: but I think it actually reveals something fairly profound, in
Speaker 3: this case about medicine, medical science, and human psychology. So
Speaker 3: the prize was awarded to and as always I apologize
Speaker 3: if I'm mispronouncing anything here, but it was awarded to
Speaker 3: Leaven A. Shank Tamine Fedai and Christian Bukele, for quote
Speaker 3: demonstrating that fake medicine that causes painful side effects can
Speaker 3: be more effective than fake medicine that does not cause
Speaker 3: painful side effects.
Speaker 2: Huh, well, this is funny this. I believe we've touched
Speaker 2: on this idea before, like, how do you know your
Speaker 2: how do you come to believe your fake medicine is
Speaker 2: doing anything if it doesn't cause you some sort of sensation? Right?
Speaker 3: Yeah, Well, we've talked about this without necessarily having a
Speaker 3: solid empirical backing for it. Just kind of like the
Speaker 3: suspicion that if you're taking some kind of pseudo scientific
Speaker 3: cure or some snake oil or something that, if I
Speaker 3: don't know, makes you it real bad, or it gives
Speaker 3: you an upset stomach or something like that, it might
Speaker 3: help sell the idea while it's doing something.
Speaker 2: In my house, my wife and I have been watching
Speaker 2: the recent twenty twenty four comedy series on Netflix based
Speaker 2: on the de Cameron, and there is a character in
Speaker 2: that who is regularly being poisoned by his personal physician
Speaker 2: for a bunch of health maladies that he I think
Speaker 2: mostly doesn't have, maybe some of them he has but
Speaker 2: you know, he's kind of a hypochondriac, and he's enabled
Speaker 2: by this doctor who's always giving him various tonics and potions.
Speaker 3: Enjoying this mercury. Yeah, yeah, yeah.
Speaker 2: So he's constantly in ill health and in large part
Speaker 2: due to these treatments, and people at times pointed out
Speaker 2: to him it's like like this guy's been poisoning you. Like,
Speaker 2: of course you feel bad. What did he give you
Speaker 2: to have today? And he's like, well, well, yes, I vomited,
Speaker 2: Yes I had uncontrollable diary. But that's what healing is, like,
Speaker 2: that's the sickness leaving your body. You know.
Speaker 3: Wow.
Speaker 2: And he's really slow to doubt this position at all.
Speaker 3: Well, it's amazing how well that exact situation will play
Speaker 3: into the study and into legitimate medical uses of place.
Speaker 3: Ebos So the authors of this paper, which by the way,
Speaker 3: for the citation, the paper was called how side Effects
Speaker 3: can Improve Treatment Efficacy a randomized Trial. This was in
Speaker 3: the journal Brain in twenty twenty four, and the authors
Speaker 3: start by pointing out the obvious side effects from medical
Speaker 3: treatments are generally bad. We don't want them. You don't
Speaker 3: want them as a patient. You don't want your patients
Speaker 3: to have them. As a doctor, side effects can cause pain, discomfort, inconvenience,
Speaker 3: and concern, and in a lot of cases there if
Speaker 3: you think about the second order effects, they're not only
Speaker 3: bad because of the direct subjective unpleasantness of them. They
Speaker 3: can also lead to discontinuation of treatment itself. So if
Speaker 3: you're taking something, you know, a medicine that is very important,
Speaker 3: that's you know, helping treat your cancer or something like that,
Speaker 3: but the side effects are really bad in some cases,
Speaker 3: that can lead people to discontinue treatment that is working.
Speaker 3: So you want to avoid side effects most of the time, obviously,
Speaker 3: and this means that the researcher is developing new drugs, surgeries,
Speaker 3: and other types of treatments are always looking to find
Speaker 3: a treatment with fewer or less severe side effects on average. Furthermore,
Speaker 3: avoiding side effects also factors into which treatments doctors will
Speaker 3: prescribe or recommend to their patients, or even into how
Speaker 3: doctors sort of mentally or conversationally prepare their patients for
Speaker 3: treatments that they do prescribe. Because much in the same
Speaker 3: way that there is a placebo effect, and the placebo
Speaker 3: effect is the effect in which the belief that you
Speaker 3: are receiving an effective treatment can by itself improve outcomes.
Speaker 3: There is also the evil twin of the placebo effect,
Speaker 3: the no cibo effect, in which the mere belief that
Speaker 3: a treatment will cause pain or other negative side effects
Speaker 3: does actually cause them. That makes sense, So it works
Speaker 3: both ways. You know, I give you a sugar pill
Speaker 3: that does nothing, but I tell you it's going to
Speaker 3: treat your pain. In a lot of cases, people will
Speaker 3: actually feel less pain. There's a psychological effect going on
Speaker 3: that causes them to subjectively feel relief. Same thing happens
Speaker 3: the other way. I give you an inert sugar pill
Speaker 3: and tell you it's likely to cause severe abdominal pain.
Speaker 3: A lot of people probably will feel severe abdominal pain
Speaker 3: even though the pill isn't actually doing it.
Speaker 2: Yeah, I feel myself wrestling with this every time I
Speaker 2: get said, like my annual flu shot, you know, and
Speaker 2: you know, I have that day after where I'm I
Speaker 2: might have some flu like you know, symptoms as part
Speaker 2: of that. But then I'm like wrestling with it. It's like, okay,
Speaker 2: but is this really happening? Like how much of this
Speaker 2: is real? How much of this is my mind? You know,
Speaker 2: engaging in the no cebo effect. So yeah, it is
Speaker 2: a real, real.
Speaker 3: Thing, absolutely, And so this leads back to this question
Speaker 3: about you know, doctors prescribing their patients treatments that do
Speaker 3: have known side effects. Because with the knowledge that the
Speaker 3: expectation of bad side effects can actually make people feel
Speaker 3: bad side effects or make bad side effects worse, doctors
Speaker 3: have to be careful like how they approach the topic.
Speaker 3: You have to be honest with patients. You know, you
Speaker 3: want transparency and full disclosure about common side effects. So good,
Speaker 3: good doctors aren't going to try to hide to the
Speaker 3: fact that there are no known side effects, but also
Speaker 3: talking about side effects the wrong way in a way
Speaker 3: that maybe increases their salience could kind of no sebo
Speaker 3: effect conjure them into a painful reality for the patient.
Speaker 3: So it's a delicate balance. You know, if you're a doctor,
Speaker 3: you have to be honest about what side effects are,
Speaker 3: but you don't want to make them worse by emphasizing
Speaker 3: them in scary ways to the patient. So anyway, that's
Speaker 3: all the background. Side effects are something that are a
Speaker 3: very important part of medicine and something that doctors have
Speaker 3: to take a lot of care about but while acknowledging
Speaker 3: that side effects are generally bad the author's right quote. Here,
Speaker 3: we challenge this view and ask whether some side effects
Speaker 3: could actually lead to better treatment outcomes. This idea is
Speaker 3: motivated by the observation that side effects themselves can contribute
Speaker 3: to treatment expectations. Our hypothesis posits that even mild side
Speaker 3: effects can be indirect indicators of treatment potent c e g.
Speaker 3: Side Effects are unavoidable with a powerful drug, which can
Speaker 3: lead to positive treatment expectations. These treatment expectations are the
Speaker 3: basis for non specific therapeutic effects i e. The placebo
Speaker 3: effect that have substantial impact on treatment outcomes. So, to paraphrase,
Speaker 3: this is sort of coming back on the other side
Speaker 3: and saying we think that negative side effects could in
Speaker 3: some cases perversely lead to better outcomes for people overall,
Speaker 3: because certain side effects might make it really feel like
Speaker 3: the drug is working. Wow, it's in there, it's really
Speaker 3: doing something, and I can tell because of the way
Speaker 3: I'm feeling because of that, you know, tingling or whatever,
Speaker 3: which increases the positive contribution of placebo effects to the
Speaker 3: overall improvement in well being you get from a treatment.
Speaker 3: And this is backed up by the fact that various
Speaker 3: non therapeutic characteristics of placebos, like the color of a pill,
Speaker 3: or the understood price of a pill, or the taste
Speaker 3: of a pill, have all been shown in previous experiments
Speaker 3: to have effect an effect on outcomes, presumably through the
Speaker 3: placebo effect. Now, in their introduction, the author's right about
Speaker 3: how there's already some reason to think this hypothesis could
Speaker 3: be true, in part because of the use of what
Speaker 3: are called active placebos over inert placebos in clinical practice.
Speaker 3: So in both cases, the drug being prescribed is a placebo.
Speaker 3: It does not act directly on the underlying issue. It's
Speaker 3: not assumed to have a biological effect. It works by
Speaker 3: triggering the psychological placebo effect. So when you give somebody
Speaker 3: a placebo, you could give them a treatment that does
Speaker 3: basically nothing in reality other than trigger the psychological effect.
Speaker 3: That would be an inert placebo. Maybe it's a sugar
Speaker 3: pill or something. Or you could give somebody a pill
Speaker 3: that does something that the patient can sense, and this
Speaker 3: would be an active placebo. The preference for active placebos
Speaker 3: indicates that internal feedback from the body telling the patient
Speaker 3: that the drug is doing something may help amplify good
Speaker 3: placebo effects overall. The author's raise another important issue, which
Speaker 3: is that if side effect do have an effect on
Speaker 3: treatment outcomes, for example, by increasing the placebo effect of
Speaker 3: a given treatment, this is useful useful information in designing
Speaker 3: randomized clinical trials. You would need to take that fact
Speaker 3: into account in designing your experiments and evaluating results when
Speaker 3: testing actual drug treatments. We can talk more about this
Speaker 3: when we get to their conclusions. Anyway, the author is
Speaker 3: designed an experiment to test whether mild negative side effects
Speaker 3: would increase the placebo effect of a fake treatment, specifically
Speaker 3: a fake pain medication. So this study involved a preregistered
Speaker 3: trial of seventy seven healthy participants who would be subjected
Speaker 3: to non injurious pain from what's called a thermode, which
Speaker 3: is a device that stimulates the skin with heat or
Speaker 3: cold used for experiments like this. It can stimulate with
Speaker 3: heat or cold that will be unpleasant. It will cause
Speaker 3: a painful reaction, but doesn't hurt you. Before getting stuck
Speaker 3: with the thermo, the participants here were given a nasal
Speaker 3: spray and told that the spray might or might not
Speaker 3: include a dose of the painkiller fentanyl. Now, in fact,
Speaker 3: none of the sprays included any pain medication instead, the
Speaker 3: independent variable was whether the spray was relatively inert saline
Speaker 3: or whether it contained capsaisin, the alkaloid found in chili peppers,
Speaker 3: which of course causes a burning sensation, so in this
Speaker 3: case it would cause some burning and irritation in the nose. Now,
Speaker 3: the researchers tested this across several different experiments with some
Speaker 3: different conditions, with later phases involving a functional MRI evaluation
Speaker 3: as well as a control group who were told that
Speaker 3: there was actually no pain medication in any of the
Speaker 3: spray and so what did they find? Bingo? Even though
Speaker 3: none of the sprays actually had painkillers in them, the
Speaker 3: spray that caused a burning sensation in the nose due
Speaker 3: to this chili pepper alkaloid also apparently caused the people
Speaker 3: who received it, believing it might be a painkiller, to
Speaker 3: experience less pain from the thermode. Now, there was a
Speaker 3: commentary piece accompanying this study, also published in Brain in
Speaker 3: twenty twenty four by Kacia Witch, Helena Hartman, and Ulrique
Speaker 3: Bingle called side effects are often a curse? Can they
Speaker 3: also be a blessing? And the authors of the commentary
Speaker 3: piece right quote crucially, this greater analgesic effect, meaning pain
Speaker 3: numbing effect. This greater analgesic effect was dependent on participants
Speaker 3: believing that the occurrence of side effects indicates a more
Speaker 3: potent treatment, with this belief leading to more positive treatment expectations,
Speaker 3: which in turn resulted in increased analgesia. So does that
Speaker 3: make sense. In order for this effect to work, the
Speaker 3: patients had to believe that the burning sensation in the
Speaker 3: knows was an indicator that the drug was really working.
Speaker 2: Yes, yeah, Like, I think we've referenced this in the
Speaker 2: in the past. You know, this idea that you're taking
Speaker 2: something it is you know, it is a placebo or
Speaker 2: a snake oil if you will, but something is happening,
Speaker 2: and then you can connect that's something to what you
Speaker 2: are promised the substance will do.
Speaker 3: Yeah.
Speaker 2: Like, I always think back to an old episode of
Speaker 2: the Andy Griffith Show that I remember watching as a
Speaker 2: kid where Aunt b is buying some sort of a
Speaker 2: medicine from some guy. You know, it's a typical typical
Speaker 2: Andy Griffith Show format where there's some sort of outsider
Speaker 2: in town doing something and people were buying into their
Speaker 2: their act and then Andy Griffith has to, you know,
Speaker 2: investigate figure it out, and it turns out it's like
Speaker 2: the substance is like eighty five percent alcohol. So the
Speaker 2: various you know, old ladies around town that are that
Speaker 2: this guy's selling to, you know, they're just enjoying a
Speaker 2: little like moonshine or something. Yeah, but since it is alcohol,
Speaker 2: they are experiencing an effect. That effect is not really
Speaker 2: curing anything, but they can associate that sensation with the
Speaker 2: idea that it is working.
Speaker 3: Yes, exactly, and that connects to something that Whych and
Speaker 3: co authors in this commentary piece right about they say
Speaker 3: quote speaking of the authors of this study, they suggest
Speaker 3: that during treatment, our assessment of drug effects may be
Speaker 3: guided by simple heuristics e g. More potent treatments have
Speaker 3: more side effects, which may not always hold true, but
Speaker 3: are often a reasonable first approximation. So this might not
Speaker 3: be a true generalizable statement about medicine, but it works
Speaker 3: well enough that many of us just operate on this
Speaker 3: assumption big side effects, very potent cure. Coming back to
Speaker 3: the quote from Whychet. Although quote remarkably, Shank and colleagues
Speaker 3: found that the latter belief was strong enough to resurface
Speaker 3: even after participants had been briefed about the active placebo manipulation.
Speaker 3: While the analgesia enhancing effect of side effects disappeared immediately
Speaker 3: after the debriefing prior to the second session, it re
Speaker 3: emerged in a follow up session conducted about a week later.
Speaker 3: So they had a condition where you know that people
Speaker 3: had been doing these trials and then with one group
Speaker 3: they explained to them, Okay, here's what's going on. You're
Speaker 3: not actually getting any painkiller. This is not really happening,
Speaker 3: and so that immediately killed the effect. It broke the
Speaker 3: illusion for the people in that group. But then the
Speaker 3: people in that group who had had the illusion already broken,
Speaker 3: they came back a week later, and then the effect
Speaker 3: was working again, even though they knew what was going
Speaker 3: on at that point. It's like the time lag just
Speaker 3: allowed the somehow allowed that the magic to re coalesce
Speaker 3: or something.
Speaker 2: Oh wow, that's impressive. Like it's like there's still like
Speaker 2: a subconscious level, like there's still like an A and
Speaker 2: a B connecting there for them and they're like, yeah, yeah,
Speaker 2: made me itch or it made me sneeze. It's working.
Speaker 3: That's a right. So the authors say that this suggests
Speaker 3: it may just be a kind of deeply conditioned general
Speaker 3: association between stronger side effects a and stronger potency as
Speaker 3: a cure. So to temper these results a bit, one
Speaker 3: thing worth noting is that the effect observed from having
Speaker 3: side effects was not huge. It was not like a
Speaker 3: you know, life changing kind of difference in how effective
Speaker 3: these placebos were. But it was a statistically significant difference,
Speaker 3: and so this could potentially be influential in treatment settings
Speaker 3: and in clinical trials. So in the end, the authors
Speaker 3: say their experiments show that mild negative side effects can
Speaker 3: make a treatment or a placebo feel subjectively more powerful
Speaker 3: and effective at its desired goal. And this leads to
Speaker 3: some kind of wild sounding suggestions in their conclusion. First
Speaker 3: of all, they write, quote one could even think of
Speaker 3: artificially changing the formulation of an established drug to include
Speaker 3: mild side effects to increase treatment expectations. However, while research
Speaker 3: on open label placebo provides the idea that this effect
Speaker 3: could be used without deception, great care would be necessary
Speaker 3: to avoid any unintended harm. So I don't know. To
Speaker 3: stick with the capsaosm theme, maybe you like you smear
Speaker 3: all pills with ghost pepper juice to make sure they
Speaker 3: burn a little bit going down.
Speaker 2: Yeah, yeah, I mean I was thinking along these lines
Speaker 2: as well, but I guess, yeah, it raises a number
Speaker 2: of questions, like what if by doing this or something
Speaker 2: like this, this actually made the individual a little less
Speaker 2: likely to take the medicine or a little more likely
Speaker 2: to reject the medicine. Yeah, you know that could be
Speaker 2: a factor. Also, It's like anytime you add any substance
Speaker 2: to a medication, that open potentially opens up the space
Speaker 2: for various other health scenarios to come into play, allergies
Speaker 2: and so forth, right, exactly.
Speaker 3: Yeah, So the authors acknowledge that is a very controversial suggestion,
Speaker 3: and it would be it would face strong ethical considerations.
Speaker 3: You'd really have to think about what are the costs
Speaker 3: and benefits of doing something like that, And of course
Speaker 3: they acknowledge, like you couldn't do that secretly, Like you'd
Speaker 3: have to find a way of being transparent about the
Speaker 3: fact that like there, yeah, there's some spicy juice on
Speaker 3: this pill or something without it destroying the placebo effect
Speaker 3: benefit that you would get from it. Yeah, it's kind
Speaker 3: of hard to work out how you would balance that.
Speaker 2: Yeah.
Speaker 3: The authors also point out that there are probably limits
Speaker 3: as to how severe the side effects could be to
Speaker 3: trigger this effect, Like we don't know because it hasn't
Speaker 3: been tested yet, but like extreme pain and discomfort would
Speaker 3: likely not produce the same outcomes. In addition to being
Speaker 3: undesirable in the first place, there's probably like a sweet
Speaker 3: spot of some kind of I don't know, mildly irritating
Speaker 3: side effect that really makes it feel like the drug
Speaker 3: is more powerful, makes you feel subjectively better overall, but
Speaker 3: is not annoying or painful enough on its own to
Speaker 3: counteract that. Maybe something in the mild tingling zone.
Speaker 2: Now I don't think they got into this, but it
Speaker 2: does make me wonder about like just sort of like
Speaker 2: the bitter taste of a pill, you know, yeah, like
Speaker 2: like something that simple as sort of reminding you, oh, yeah,
Speaker 2: this is medicine I'm taking.
Speaker 3: Yeah. However, they offer so you know, the author, the
Speaker 3: original authors, and the people in the commentary piece, they're
Speaker 3: all saying, like, Okay, that idea is a little bit wild.
Speaker 3: That's kind of controversial to say you would intentionally increase
Speaker 3: mild negative side effects to make the placebo aspects of
Speaker 3: a treatment better. So they offer a different idea, which
Speaker 3: is you could potentially capitalize on this discovery by saying,
Speaker 3: when side effects are already present in a drug, doctors
Speaker 3: could try to increase the positive salience of known side effects,
Speaker 3: unavoidable known side effects instead of trying to decrease the
Speaker 3: salience of those side effects. So, you know, we talked
Speaker 3: at the beginning about how a lot of doctors know
Speaker 3: about no cebo effects, and so they will often try
Speaker 3: to frame the possibility of negative side effects in a
Speaker 3: delicate way to try to prevent them from you know,
Speaker 3: prevent them from over manifesting due to no sebo expectations.
Speaker 3: The authors here are saying, well, what if you kind
Speaker 3: of do the opposite, maybe kind of elevate the salience
Speaker 3: of mild, known unavoidable side effects of drugs, but you
Speaker 3: frame them in a positive way instead of a negative way.
Speaker 3: So you frame unavoidable pre existing side effects of drugs
Speaker 3: as a sign that it's working.
Speaker 2: All right, all right, I can I can see. This
Speaker 2: is just more about the messaging and turning the potential
Speaker 2: negative into.
Speaker 3: A positive exactly. Yeah, So being honest about what the
Speaker 3: side effects are, but framing it in a way that
Speaker 3: emphasizes these positive placebo effects, you would get from those
Speaker 3: side effects. Yeah, However, all the authors involved here clearly
Speaker 3: acknowledge that this is a delicate, tricky subject area because,
Speaker 3: as the authors of the commentary piece right quote, the
Speaker 3: framing of side effects must respect ethical standards and should
Speaker 3: not jeopardize patient autonomy and the patient practitioner relationship. It's
Speaker 3: therefore crucial for patients and practitioners to engage in joint
Speaker 3: decision making about the use of positive framing as part
Speaker 3: of the treatment. So, you know, they're saying there, like,
Speaker 3: you want to be as transparent as possible while doing
Speaker 3: this because if the patient, I mean, for one thing,
Speaker 3: that's just like baseline what a doctor should do. But
Speaker 3: also if the patient gets the feeling that they're being
Speaker 3: manipulated or the doctor is not being honest with them,
Speaker 3: then also this could lead to more negative treatment outcomes
Speaker 3: and everything. So, like, I don't know, it's a difficult
Speaker 3: thing to work out here because there the placebo effect,
Speaker 3: no cebo effect. It all necessarily relies on some amount
Speaker 3: of illusion. But you can't let that manifest as dishonesty
Speaker 3: in the clinical setting or any kind of lack of
Speaker 3: trust between the doctor and the patient.
Speaker 2: Yeah, that's a great point because you're you're you're in
Speaker 2: this realm where on one hand, you have you know,
Speaker 2: pretty hard lines concerning you know, ethical medicine and doing
Speaker 2: no harm and being transparent. But then also you were
Speaker 2: you were in that space of bedside manner, which can
Speaker 2: be kind of subjective, and it's going to may vary
Speaker 2: from patient to patient. You know, one patient may be like,
Speaker 2: you know, tell it to me straight, doc, don't sugarcoat it.
Speaker 2: Other you know, I like a little sugarcoating. Sugarcoat it
Speaker 2: for me a little bit, doc. You know, I want
Speaker 2: to feel okay when I leave. You know, in.
Speaker 3: Research shows sometimes sugarcoating can literally help.
Speaker 2: Yeah. Yeah, So I mean it's you can you can
Speaker 2: imagine it's going to differ from persons. And then on
Speaker 2: top of all this, as you've been pointing out, like
Speaker 2: there's an illusion that is taking place, But to what extent,
Speaker 2: sorry for this, can doctors use that illusion to their benefit?
Speaker 3: Yeah? I don't know exactly what the answer is there.
Speaker 3: I mean it kind of makes me think of like
Speaker 3: the contract you enter into with some stage magicians. You know,
Speaker 3: like a stage magician is going to show you a
Speaker 3: bunch of tricks that appear to be magic, but you know,
Speaker 3: a lot of I don't know. Some might insist that
Speaker 3: it's really magic, but mostly stage magicians are going to overall,
Speaker 3: they will be transparent and say, no, I don't actually
Speaker 3: have magic powers. These are all illusions, These are all tricks,
Speaker 3: and yet you get the audience to buy into them
Speaker 3: for the purpose of the entertainment, for the purpose of
Speaker 3: the show. And I guess there's a similar thing that
Speaker 3: has to go on in this doctor patient relationship. It's like,
Speaker 3: there must be transparency and honesty overall, but you have
Speaker 3: to get the patient into the mind space of being
Speaker 3: accepting of the illusion and the benefits it provides.
Speaker 2: Yeah. Absolutely.
Speaker 3: Now there's another consideration the authors bring up, which is
Speaker 3: clinical trials. They make the point that placebo controls are
Speaker 3: a very important part of the scientific process of testing medicine.
Speaker 3: If you want to test whether a drug is actually working,
Speaker 3: whether it's actually having a biological effect, you need to
Speaker 3: compare it not just to doing nothing, but they need
Speaker 3: to compare it to a placebo so that you can
Speaker 3: ignore the extent to which the effect you're seeing in
Speaker 3: the trials is due to placebo effects alone. So, for example,
Speaker 3: if this may be numerically crude analogy, but just to
Speaker 3: roughly illustrate the idea. If people getting the actual drug
Speaker 3: being tested see a thirty percent improvement in symptoms, but
Speaker 3: people getting a placebo see a twenty percent improvement, then
Speaker 3: you can guess that the biological effect of the drug
Speaker 3: only contributes the difference. Maybe it's only contributing about ten
Speaker 3: percent of an improvement, because if it's a well designed
Speaker 3: trial with randomized groups, you should expect the amount of
Speaker 3: placebo effect in the test group and the control group
Speaker 3: to be about the same. Does that make sense? Both
Speaker 3: groups should be benefiting from about the same amount of
Speaker 3: placebo effect, but the test group should be additionally seeing
Speaker 3: any benefit that's actually provided by the therapeutic effects of
Speaker 3: the treatment the actual biological mechanism.
Speaker 2: Yeah. Yeah, that would be measurable.
Speaker 3: Yeah yeah. So the authors here are emphasizing the point
Speaker 3: that if side effects such as like a burning sensation,
Speaker 3: you know, these small negative side effects increase the power
Speaker 3: of the placebo effect, as this study shows, they probably do.
Speaker 3: You know, of course, we'd want to see this backed
Speaker 3: up by other studies, but this is an indication that
Speaker 3: may be going on. This could be throwing off the
Speaker 3: results of clinical trials a little bit, because if the
Speaker 3: actual treatment under testing causes side effects and the placebo
Speaker 3: control does not cause side effects, the test group will
Speaker 3: benefit from more placebo effect than the control group and
Speaker 3: thus overestimate slightly the biological effect of the treatment. Now,
Speaker 3: to be clear, the authors here are not and are
Speaker 3: not claiming to be the first people ever to notice
Speaker 3: this kind of confound to RCTs. The format in which
Speaker 3: I've seen it discussed more often in the past is
Speaker 3: the idea of de blinding the placebo group in double
Speaker 3: blind RCTs. So, in order to eliminate expectation effects, test
Speaker 3: subjects in clinical trials are not supposed to know if
Speaker 3: they're in the test group or the control group. Right,
Speaker 3: You're not supposed to know if you're getting the real
Speaker 3: medicine being tested or the placebo. But if the treatment
Speaker 3: being tested takes some form that is obvious or comes
Speaker 3: with known side effects which you are obviously not experiencing
Speaker 3: in the control group, then you are effectively de blinded.
Speaker 3: You know which group you're in, and thus the result
Speaker 3: are corrupted and less reliable. And so this is a
Speaker 3: slightly different but related issue similar to that if you
Speaker 3: don't get the side effects, your placebo effect could be
Speaker 3: comparatively lower on average than the placebo effect in the
Speaker 3: test group that is getting the side effects. So are
Speaker 3: there ways around this? Well, yeah, this comes back to
Speaker 3: something that has already been implemented in clinical trials before,
Speaker 3: such as the use of active placebos. So the placebo
Speaker 3: group should be getting something that tries as closely as
Speaker 3: possible to mimic the mimic the effects of the actual
Speaker 3: treatment to heighten the illusion make it feel as similar
Speaker 3: as possible. They say, you could also, maybe I don't know, specially,
Speaker 3: design some kind of methods to avoid these complications and
Speaker 3: get the cleanest state of possible. But anyway, I thought
Speaker 3: the study was really interesting because of of course, it
Speaker 3: is pretty funny, like the idea that you're like intentionally
Speaker 3: shooting chili pepper juice up somebody's nose to make it
Speaker 3: burn in order to help them feel better overall, and
Speaker 3: the fact that this does seem to be a real
Speaker 3: significant effect that happens in our brains. I just think
Speaker 3: it's so interesting that our minds work that way, and
Speaker 3: it raises all of these difficult, really meaningful questions about
Speaker 3: treatment and about medicine, about how we do medical science
Speaker 3: and how we test new treatments and raises all these
Speaker 3: questions about how to handle the relationship between a doctor
Speaker 3: or a caregiver and their patient.
Speaker 2: Absolutely, and I think it also reminds me that there
Speaker 2: is often a mad magazine kind of sensibility I think
Speaker 2: to the Ignobel Prize selection process, in which they do
Speaker 2: like a study that, no matter how serious it is,
Speaker 2: on some level the experimentation feels like a prank. Yeah,
Speaker 2: you know, it's like, here, take these pills and then snicker.
Speaker 2: Those are spicy pills.
Speaker 3: Yeah, there is an alfredy Newman quality to this that
Speaker 3: the the capsay is in nasal spray. However, I did
Speaker 3: not in the text of the paper itself, I did
Speaker 3: not detect a lot of I don't know, perverse or
Speaker 3: sadistic snickering from the from the author is. It just
Speaker 3: seemed like, yeah, we got an idea, I got to
Speaker 3: find a way to test it.
Speaker 2: Well. I see similar elements in the next prize you're
Speaker 2: going to discuss here, that's the Botany Prize. Though in
Speaker 2: this case, if there is, if there is any interpretation
Speaker 2: of a prank here and likewise, it's not This is
Speaker 2: not something that is acknowledged in the paper itself, but
Speaker 2: if you were to interpret it as such, the prank
Speaker 2: is being pulled off on a plant by you. Jokes
Speaker 2: on you, Yeah, jokes on you plant. So the Botany
Speaker 2: Prize this year went to a twenty twenty two paper
Speaker 2: published in the Gym Plant Signaling and Behavior with the
Speaker 2: title Boquilla Trifoliolata Mimics Leaves of an Artificial plastic host
Speaker 2: plant by Jacob White and Felipe Yamashita. The humor here,
Speaker 2: it would seem, is found in the idea that a
Speaker 2: living plant is mimicking a fake plant, which of course
Speaker 2: is itself a feat of mimicry carried out by humans
Speaker 2: through their plastic technology. Wow, but this is one where okay, yeah,
Speaker 2: it makes you laugh, but then definitely makes you think,
Speaker 2: because I really have to stress that the underlying science
Speaker 2: here is really phenomenal, even just the overview of everything
Speaker 2: prior to this twenty twenty two paper, like the more
Speaker 2: generally widely accepted material, really raises so many questions about
Speaker 2: not only be trifoliolata but also plants in general. You know,
Speaker 2: it forces you and there are a lot of subjects
Speaker 2: like this in the realm of botany that really makes
Speaker 2: you view them with new eyes because because the thing
Speaker 2: about plants is, if you're lucky, plants are all around you.
Speaker 2: You know, if you live in an environment that has
Speaker 2: a lot of flora, it's there. It's enriching your life.
Speaker 2: But it's easy to take for granted. It's easy to
Speaker 2: not notice unless it's actually getting in your way or
Speaker 2: you know, hitting you in a weak moment where you're
Speaker 2: open to its beauty. But for the most part, yeah,
Speaker 2: it's like trees are there. We know they're alive, but
Speaker 2: we don't think of them as really active parts of
Speaker 2: the environment. We think of them as these passive things.
Speaker 3: We underappreciate them, I think because the time scale of
Speaker 3: their activities and the physical changes triggered by their activities
Speaker 3: is longer than we're you used to with animals. So
Speaker 3: we're like really much more impressed by things that move
Speaker 3: and react quickly, and because plants don't tend to move
Speaker 3: and react quickly, like on the timescale of seconds, though
Speaker 3: in a few cases they do, you know, venus fly
Speaker 3: traps and shrinking flowers and all that, but in most cases,
Speaker 3: they don't react on the timescale of seconds. We just
Speaker 3: tend to think of them as inanimate objects therefore, but
Speaker 3: like when you actually see how they react to things
Speaker 3: and what they do over time, they can start to
Speaker 3: feel a lot more alive. And even this could be
Speaker 3: misleading in some ways, but even in some ways intelligent.
Speaker 2: Yeah, and that definitely plays into interpretations of this particular
Speaker 2: plant species. Now, to be clear, the plant in question
Speaker 2: here be trifoliolata, has been around for a very long time,
Speaker 2: known locally in its native regions of South America is
Speaker 2: vokey blanco or pill pill. Indigenous medicine has made use
Speaker 2: of its leaf juice, and the vines have long been
Speaker 2: used in basketry, so this is not something that is
Speaker 2: just entirely new now. In essence, this species is a
Speaker 2: non parasitic vine that coils around other plants for structure
Speaker 2: and protection. It bears little white flowers, edible little fruits,
Speaker 2: and overall nothing is really astounding about that, right. I mean,
Speaker 2: you can look up pictures of this plant and it
Speaker 2: does not look exciting if you do not know what
Speaker 2: to look for, or you don't have things about what
Speaker 2: it's doing pointed out to you. I included a picture
Speaker 2: of it here for you, Joe. I mean, what can
Speaker 2: you say green plants? Right?
Speaker 3: I mean I see a nice elegant, deep green, waxy
Speaker 3: leaf arranged in a three leaf shape coming off of
Speaker 3: the stalk. Yeah, it's a pretty little plant. But it's
Speaker 3: I don't know if it would really catch my attention.
Speaker 3: It's just a little little vine with green leaves.
Speaker 2: Yeah. Yeah, Like would you stop and look at it
Speaker 2: in a walk? Maybe not unless you really were paying
Speaker 2: close attention and you figured out what was going on here.
Speaker 2: So European descriptions of this plant date back to the
Speaker 2: late eighteenth century, but some of the most astounding discoveries
Speaker 2: are rather recent, centered around the work of plants scientists
Speaker 2: or Nesto Again and Fernando carrasco Ura and the discovery
Speaker 2: and key to all this their discovery that the plants
Speaker 2: leaves actually mimic the leaves of nearby plants. You know,
Speaker 2: especially in this context that the plant that it is
Speaker 2: coiled around, but also just nearby plants in general. And
Speaker 2: to be clear, this is not a case in which
Speaker 2: a plant has evolved to feature leaves that mimic the
Speaker 2: leaves of a common host plant. Though this is you know,
Speaker 2: in and of itself, this would be a pretty amazing
Speaker 2: feat as well. I mean, plant mimicry of this sort
Speaker 2: of which there are some remarkable examples, is amazing.
Speaker 3: Right, But you're not saying it's just like a static
Speaker 3: form that has evolved over time to resemble plants that
Speaker 3: it is usually around in its environment.
Speaker 2: Right right. What the researchers quickly figured out here is
Speaker 2: that this is an example of botanical mimicry that occurs
Speaker 2: as the plant grows, and it can mimic most different
Speaker 2: plants in its immediate vicinity, and nothing else like this
Speaker 2: is known to exist in the plant world.
Speaker 3: Now, that is really interesting, and I would immediately be
Speaker 3: curious to know how does it do that? How does
Speaker 3: it how does it determine the shape of the leaves
Speaker 3: of plants around it?
Speaker 2: Yeah, because, I mean, another thing the research has discovered
Speaker 2: is that it can mimic the leaf shape, the leafs,
Speaker 2: the leaf size, even the color. And it can do
Speaker 2: this for more than a dozen different plants. In fact,
Speaker 2: different parts of the same plant can mimic different plants.
Speaker 2: So you know, I instantly, you know, thought about horror
Speaker 2: movies and reminded me of how in John Carpenter Is
Speaker 2: the Thing, we get some of those scenes late in
Speaker 2: the film where we catch the titular alien creature mimicking
Speaker 2: several different victims at once. You know, here's this person,
Speaker 2: here's this person, here's the dog, and so forth, and
Speaker 2: you know, but the reality is that this plant really
Speaker 2: is a shape shifter. It is really doing the shape shifting.
Speaker 2: It is just doing it on the timeframe of a plant,
Speaker 2: and just as the thing shape shifts in order to survive.
Speaker 2: That's inevitably the case here, and the exact reason. You know,
Speaker 2: it's always a little ambiguous figuring out exactly why organisms
Speaker 2: have evolved in the things they do. But it's thought
Speaker 2: that this might be to protect itself against certain snails
Speaker 2: and beetles by resembling less tasty plants in its vicinity.
Speaker 2: So essentially a form of Batitian mimicry. But to your question,
Speaker 2: how does this work? Like, what are the possible mechanisms
Speaker 2: in play here? How do they sense the different leaves
Speaker 2: in their vicinity and then.
Speaker 3: Copy them exactly.
Speaker 2: Yeah, and this is where we get into some interesting
Speaker 2: hypotheses and also a pronounced divide in the world of
Speaker 2: interpreting what's going on when plants engage in this kind
Speaker 2: of behavior.
Speaker 3: Okay, so some of the ideas we're about to get
Speaker 3: into are fairly controversial or not settled.
Speaker 2: Right right. I was reading a great commentary on this study.
Speaker 2: This is from twenty twenty three. It appeared in Vox
Speaker 2: by Benji Jones titled the Mystery of the Mimic Plant,
Speaker 2: and Jones here stresses that you can divide the hypothesizers
Speaker 2: up into two distinct groups. Here, on one hand, you
Speaker 2: have mainstream botanist and then on the other hand, you
Speaker 2: have scientists with ideas in plant cognition and related areas
Speaker 2: that really challenge our understanding of what plants are in
Speaker 2: how plants match up to animals. And these two groups
Speaker 2: don't necessarily see eye to eye on everything. The mainstream
Speaker 2: botanists their views are going to be more widely accepted,
Speaker 2: and people in the plant cognition area, and particularly in
Speaker 2: this area of plant neurobiology, some of their ideas are
Speaker 2: going to be perhaps a little more out there. I
Speaker 2: don't want to dismiss what they're doing or anything, but
Speaker 2: just suffice to say there is a starch divide, and
Speaker 2: there is a you know, an area of disagree between
Speaker 2: these two camps, with the mainstream botanists being really the
Speaker 2: more widely accepted view on things as I understand.
Speaker 3: It, So we could say among among experts there's sort
Speaker 3: of a majority position in a minority position.
Speaker 2: Yes, So on that mainstream botany track, we have the
Speaker 2: likes of Ernesto Gianoli and Fernando carrasco Ura, who definitely
Speaker 2: lean more towards the idea that, Okay, what's going on here?
Speaker 2: We can look to a couple of primary possibilities. One
Speaker 2: is that the plant is picking up on chemical volatile
Speaker 2: signals released from the host plant. They also propose the
Speaker 2: possibility that there is horizontal gene transfer going on via microbes,
Speaker 2: and it's also possible. They state that both of these
Speaker 2: are going on at once, and that the planned here
Speaker 2: be Trifoliolata is essentially speaking multiple plant micro languages to
Speaker 2: pull off this mimicry.
Speaker 3: Okay, So if I'm understanding this right, it would be
Speaker 3: that the plant somehow has a it's got a plan
Speaker 3: within it that if it picks up the chemical signature
Speaker 3: of different types of other plants in its vicinity, that
Speaker 3: can trigger it to grow in different patterns that resemble
Speaker 3: those plants, and that would be some kind of evolved response,
Speaker 3: or it could be through this microbial pathway through bacteria
Speaker 3: or some other microbes, be getting genetic material from other
Speaker 3: plants in its vicinity that are somehow contributing to this
Speaker 3: shaping process.
Speaker 2: Right right, So that's those are some of the key
Speaker 2: hypotheses that are used by these researchers. And again, if
Speaker 2: this is indeed the case, this is already amazing. You
Speaker 2: know this, this this vine is able to do this.
Speaker 2: But then there's this additional hypothesis, and this is the
Speaker 2: one that's explored in the Agnobel winning paper, the hypothesis
Speaker 2: that the plant is truly using some form of sight
Speaker 2: or something as close to site as we can really
Speaker 2: discuss in plants versus animals, and they're able to see
Speaker 2: what's around them. And in this we dip into the
Speaker 2: concept of plant ocelli, something that mainstream botanists tend to
Speaker 2: view with a great deal of skepticism. Some in the
Speaker 2: plant cognition world, particularly the plant neurobiologists, however, or more
Speaker 2: open to this idea and even concepts that plants depend
Speaker 2: on something more or less like a brain not in
Speaker 2: the sense that it looks like a brain, but in
Speaker 2: the sense that, for instance, they often point to neuron
Speaker 2: like cells in parts of a plant's roots as a
Speaker 2: possible sort of cognition aticenter.
Speaker 3: Now correct me if I'm wrong, But from what I understand,
Speaker 3: it would not be controversial to suggest that plants have
Speaker 3: some light sensing abilities. What would be more controversial would
Speaker 3: be the idea that their light sensing abilities are anything
Speaker 3: like sight, anything that could create a detailed picture of
Speaker 3: the surrounding environment from which you could actually copy growth patterns.
Speaker 2: Yeah. Yeah, Because obviously plants have a special relationship with
Speaker 2: the sun. They like most organisms that have a relationship
Speaker 2: with the sun, they know they can't react to some light.
Speaker 2: They can detect the light via photoreceptors. That's not in question.
Speaker 2: But it comes down to this idea that they are
Speaker 2: on some level seeing and the plant o cell. The
Speaker 2: idea actually goes back to nineteen oh five and the
Speaker 2: work of Austrian botanist gautlub Haberlant, who some Ludwig, by
Speaker 2: the way, is considered the father of hormonal contraception. But
Speaker 2: he proposed in nineteen oh five that the upper epidermis
Speaker 2: cells of a plant boast a convex shape that acts
Speaker 2: as a lens which focuses light into light sensitive sub
Speaker 2: epidermal cells, and that this would essentially serve as a
Speaker 2: form of sight. Now, this is not accepted really widely
Speaker 2: accepted by mainstream botanists. But this is where we get
Speaker 2: into the Ignobel Award winning study from twenty twenty two
Speaker 2: with Yamashida and White, again published in Plant Signaling and Behavior.
Speaker 2: The researchers here are set out to test all of
Speaker 2: this out via the use of artificial plastic plants with
Speaker 2: characteristic leaf shapes. And the idea here is that any
Speaker 2: mimicry that they could observe in this experiment, which would
Speaker 2: involve putting plants real and fake in a window exposed
Speaker 2: to sunlight and seeing how they responded, the idea is, Okay,
Speaker 2: if any mimicry takes place between our real living plant B.
Speaker 2: Trifoiliolata and a plastic plant, well, it can't possibly be
Speaker 2: horizontal gene transfer because plastic plant has no genes, and
Speaker 2: it can't be chemical volatile signals because again plastic plant
Speaker 2: has none of that. It just has leaf shapes and colors.
Speaker 3: Yeah, the only way in which it resembles a plant
Speaker 3: is by looking like one.
Speaker 2: Yeah, And so they conducted this experiment which they lay
Speaker 2: out on the paper, and they say, yes, like, these
Speaker 2: results show that the plant in question was able to
Speaker 2: mimic the leaf shapes around it, even those of those
Speaker 2: leaf shapes were fake plastic plants.
Speaker 3: Now I'm simultaneously thrilled by and skeptical of that. That's like,
Speaker 3: super interesting if it's true, But I feel like I
Speaker 3: would want to see that replicated a number of times.
Speaker 2: Yeah. Yeah. And the Vox article that I referenced earlier,
Speaker 2: it points out and talks to some critics of this
Speaker 2: that points out that a lot of mainstream botanists have
Speaker 2: issues with this study and or its findings. I want
Speaker 2: to read a quick quote from it. Several scientists told
Speaker 2: Vox that there are significant issues with the study design.
Speaker 2: The authors didn't adequately control variables that can influence leaf shapes,
Speaker 2: such as the age of the leafs, for example. They said.
Speaker 2: Mainstream researchers also challenge the underlying theory plant vision. Certain
Speaker 2: plant cells may be able to act like lenses that
Speaker 2: can focus light, but they likely can't create any sort
Speaker 2: of detailed pictures.
Speaker 3: Well, that certainly sounds like a good reason for tempering
Speaker 3: enthusiasm about this result. But I'm interested in the open question.
Speaker 3: I would want to see the studied more.
Speaker 2: Yeah, yeah, I would like to see some more research
Speaker 2: in this area to see exactly how far we can
Speaker 2: really go with this. But and I don't think we're
Speaker 2: there yet. But in general, I thought it was interesting
Speaker 2: that this study does highlight this divide between mainstream botany
Speaker 2: and those closer to the realm of plant neurobiologists, you know,
Speaker 2: and it raises a lot of questions, like, you know,
Speaker 2: plants are amazing, but are they more like animals than
Speaker 2: we give them credit for? On some level? Do we
Speaker 2: need them to be more like animals? Is there a
Speaker 2: strong case to be made for something like plant sentience? Again,
Speaker 2: I don't want to dismiss the ideas of plant neurobiologists,
Speaker 2: but there does seem to be this disconnect. And I
Speaker 2: think if you think about like some of like the
Speaker 2: I guess the extreme versions of criticisms from both sides,
Speaker 2: Like one side might be saying you want plants to
Speaker 2: be too much like animals, and the other side might
Speaker 2: be saying like you were in denial that plants are
Speaker 2: as much like animals as they are. And you know,
Speaker 2: I guess both of these ideas could be equally correct
Speaker 2: and incorrect as generalities about the way that we relate
Speaker 2: to plants.
Speaker 3: Well, yeah, because even as I was saying at the
Speaker 3: beginning of this section, I think, without taking on any
Speaker 3: of the assumptions of plant neurobiologists, or believing that plants
Speaker 3: can see in detailed pictures, or believing that plants have
Speaker 3: a brain like you know, intelligence, organ or anything like that,
Speaker 3: plants are still pretty amazing. And it's like I was saying,
Speaker 3: I think it's amazing to see the ways in which
Speaker 3: their growth patterns and stuff looks more like behavior if
Speaker 3: you manipulate the time factor and understanding what that means
Speaker 3: about how we interpret the concept of activity and intelligence
Speaker 3: in the relationship of that to time.
Speaker 2: And I think this is especially you know, true when
Speaker 2: you get into the subjects like interplant communication, you know,
Speaker 2: which I think we've touched on in the show before,
Speaker 2: you know, sometimes via underground networks of fung guy connecting trees.
Speaker 2: I mean, it's it's amazing, it's very it's equally at
Speaker 2: the same time, it's like it makes them more human
Speaker 2: and more inhuman, because you know, we don't use fungal
Speaker 2: networks to communicate with each other. But the fact that
Speaker 2: they do communicate with each other, like it puts it,
Speaker 2: it's a different way of looking at them. It's like
Speaker 2: realizing there's there's something going on here that is in
Speaker 2: many ways more like what we as humans do, though
Speaker 2: it of course is in a totally different branch of
Speaker 2: the whole tree.
Speaker 3: Whether animal intelligence is an appropriate analogy or not, what's
Speaker 3: objectively happening is really interesting.
Speaker 2: Yeah, absolutely so. Again like true to form, you know,
Speaker 2: made me laugh and then made me think, you know
Speaker 2: quite a bit here about about what plants are up
Speaker 2: to or not up to when they grow their leaves
Speaker 2: in particular ways. All right, we're going to go and
Speaker 2: close this episode. Let's see. We just want to remind
Speaker 2: everybody that Stuff to Blow Your Mind is a science
Speaker 2: and culture podcast with core episodes on Tuesdays and Thursdays.
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Speaker 3: Huge thanks as always to our excellent audio producer JJ Posway.
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