Watch Episode Here
Listen to Episode Here
Show Notes
This is a ~30 minute conversation with Mayli Mertens (Marie Curie Postdoctoral fellow at University of Antwerp, https://philpeople.org/profiles/mayli-mertens) and I on the topic of molecular placebos, bioelectricity, and self-fulfilling prophecies in medicine (the latter being the title of her recent paper: https://link.springer.com/article/10.1007/s11017-024-09677-z )
CHAPTERS:
(00:00) Genetic prediction hypothesis
(03:38) Everything is placebo
(07:51) Prediction, belief, biology
(15:10) Beliefs shaping physiology
(19:26) Bioelectric cancer remissions
(24:13) Perception and future work
PRODUCED BY:
SOCIAL LINKS:
Podcast Website: https://thoughtforms-life.aipodcast.ing
YouTube: https://www.youtube.com/channel/UC3pVafx6EZqXVI2V_Efu2uw
Apple Podcasts: https://podcasts.apple.com/us/podcast/thoughtforms-life/id1805908099
Spotify: https://open.spotify.com/show/7JCmtoeH53neYyZeOZ6ym5
Twitter: https://x.com/drmichaellevin
Blog: https://thoughtforms.life
The Levin Lab: https://drmichaellevin.org
Transcript
This transcript is automatically generated; we strive for accuracy, but errors in wording or speaker identification may occur. Please verify key details when needed.
[00:00] Mayli Mertens: The paper is very conventional. It's trying to talk to people so they can use it practically. It aims to explain a way of analysis that would work in other fields and actually answer some more fundamental questions. Because of the way grant proposals work, I had to pick a very specific example and I chose genetics. The very basic idea is that if you were to receive genetic information about yourself — you had to do a DNA test — based on the risk factors of that DNA, the moment you have some cognition of that information, whether you believe it or deny it, it starts to have an impact because your body is somehow sensitive to that information and it changes gene expression just based on that information. That was the basic hypothesis. I work with people who do empirical work. I don't do the empirical work myself; I'm working on the ethics, epistemology, and metaphysics of it. Basically, I've been obsessed with trying to find out what is the employment sensitivity with cases we don't understand. I think the reason we don't understand them is because we have a framework that isn't correct or is incomplete. What I found really interesting in your work is that I think it works for genetics or epigenetic expression, and it may also work for other things like placebo in other physiology that we don't understand. I have this hypothesis, and I really liked your idea of looking forward rather than trying to explain things backwards. My hypothesis is that the part of the system — the body in this case, or the physiology — that is sensitive to prediction (I take prediction broadly) would be the bioelectric system. If that's true — if that's what, for example, could explain placebo — then I would want to know how. One big aspect I want to investigate is the relationship between our centralized cognition — the mind or consciousness or mental states — that would somehow trigger the bioelectric system and therefore create this physiological change. How does that work and what's the directionality? I don't know if it's unidirectional or bidirectional, and how would I investigate or test that? I wanted to know what you think of this hypothesis, whether you see possible explanations of how that would work. I have some ideas about people in your lab and people in the Mind and Body Lab at Stanford and how that could create a collaboration to test these things, unless you already have.
[03:38] Michael Levin: I think a couple of things. I think first of all, I think you've focused on a very important aspect of a bunch of different fields and it's going to be important for biomedicine and everything else. I gave a talk recently where I was answering some questions and talking about this issue of the collective intelligence of the body cells and solving problems in anatomical space and physiological space. I made the claim that pretty much everything is placebo in the sense that what we're dealing with are activities of an information processing system that's going to make decisions on what it does next based on its priors, based on things it believes, based on prior data and all of that. There was a short clip of just me saying "everything is placebo" that went online. I got a whole bunch of people saying, "Oh my God, I'm really sick. That isn't what I was talking about." I think what we can bring to this, and there are some amazing people studying placebo and nocebo — Fabrizio Benedetti and others — is what you were talking about, which is this idea that our brainy consciousness and those mental activities are not the only intelligence in the body, and that we need to understand the interaction between the information that that intelligence uses to form its worldview and its self-model and its model of the outside world, and how that links to the models that are being made by your cells and your tissues and your organs. I think it's a very pervasive topic that's very important in biomedicine and our attempts to control cells. The one thing we know for sure, so we know very little, but the one thing we know for sure is the problem you pointed out, which is what's the connection between our centralized integrated verbal intelligence and the rest of the body? The one thing we know for sure is that bioelectrics is the bridge to that. The reason we know this for sure is that we already know this is how voluntary motion works. When you wake up in the morning and you have very large-scale executive goals — you've got goals in financial spaces, social spaces, abstract things — your cognition is able to use them as goals and you're going to meet those goals with certain activities. In order to get up out of bed and do that, those very high-level abstract concepts eventually have to make your muscles contract so that you can get up and execute on those goals. We know the system that does that: it's neurophysiology. This has been studied for a couple of hundred years now, the idea that large-scale mental constructs eventually make the calcium and potassium ions dance across your muscle cell membranes. The interface between those mental events and the chemistry that drives your muscle motion is amazing. These ineffable mental concepts are actually making chemistry change in your muscle cells every day. People when I talk about this — I say you can, with the power of your mind alone, depolarize maybe 30% of your body cells. People think this is some kind of crazy yoga or biofeedback or some weird anomalous thing. It's just voluntary motion. It happens 24/7 in your body. So I think we know that bioelectricity is critical there. The two ends of this are the neurophysiology that connects the mental states of the human to physiological actions, and the other side is the cognitive states of the rest of the body, which are also going to make decisions in how they navigate the space of physiological states based on beliefs in those two things. We've done some work on how those two things interact.
[07:51] Mayli Mertens: Okay, maybe two questions. One would be very specific. It's just about the genetics, to explain, because I get we have to chalk this up into small parts to sell it to the scientific community. Right now, I finished a paper with a geneticist that basically maps all the different kinds of self-fulfilling and self-defeating mechanisms in genetics. A lot of them we understand; we use them to create therapeutic interventions. We mapped most of the conventional things and touched upon some that were missed in typical practice, but it's all very conventional. Now I'm trying to write a new paper that would explain a more unconventional understanding of what's really happening when it comes to genetic expression, for example, or even those sidetracks, that maybe it appears to be a change in epigenetic expression or that it appears as a genetic change, but actually what's really happening is something completely different, which is the kind of stuff that you guys are doing. That's the small version. The bigger version is important to mention because all of this stuff is very small. All of these questions I ask myself are different examples of a more fundamental concern, especially in philosophy; that's probably what keeps me up at night. I want to know what you think about that in relation to your work. For me, based on the fact you said one thing we know for sure, I feel I know nothing for sure. What it gets me thinking is whatever we know, and that's why I said I take prediction to be very, very broad in the sense that every time we say anything about anything, it still has a degree of uncertainty, which almost everything has. Everything we say about everything, if we express it with assertion or some kind of assertoric force, then we're basically making a prediction because we are inviting more credibility than maybe it deserves. I ended up specializing in ethics of prediction, even though prediction is very problematic, and I don't think we should do it as often as we do; we should at least be aware that we're predicting. My big existential concern is that given the fact that we probably have faulty assumptions, everything we know builds on the bottom ones that we cannot prove or that we don't understand. Given the fact that we have these faulty or incomplete assumptions, how come the world presents itself to our experience or presents itself to us in a way that we would expect it to? There are probably more, but I see two possibilities that I'm really torn between. Either the world presents itself to us the way we would expect it to despite our faulty assumptions, or it presents itself to us the way we expect because of our faulty assumptions. That's where it really comes down to. Can our centralized cognition or our experience of the physical world change the physical world? This whole mind over matter idea is too simplistic. That's the gist of it.
[11:49] Michael Levin: A couple of things. First, the stuff about genetics. There are two things I recommend to think about. One is if you want to stay conventional, which is not a bad idea, because in my experience, when you're writing something or giving a talk or whatever, typically people can handle one new idea. If you're saying all these different things, which I'm totally guilty of because I say all kinds of crazy stuff, typically you want one battle that you want to fight in any particular paper. So if you want it to be conventional in that way, you could say, fine, genetics is what most people are interested in. The mechanisms by which bioelectric states influence gene expression are well known. We have characterized them over the last 20 years. So you can make a pretty solid chain where, if, as neuroscientists believe, our thought, memories, beliefs, and so on are in some way encoded in the bioelectrics of neural and other networks, we now have the molecular mechanisms to say, this is how it's going to change your gene expression. There's no mystery. There's no magic step there. They're all known.
[13:20] Mayli Mertens: You're even skipping a step of how the beliefs, the mental states, the changes in our identity or our perception of identity influence the bioelectricity. You say, no, it's already in there.
[13:37] Michael Levin: I'm not trying to say that neuroscience is solved by any means. I don't think it is. But it is not a controversial claim that whatever beliefs you have about what's going to happen are in some way encoded in the electrical properties of your brain cells. This is what almost every working neuroscientist thinks, that the electrical networks, what I am doing that's a little different here is I'm purposely fuzzing over the difference between neural electricity in the brain and non-neural electricity in the rest of the body. And there's good reasons to do that. But the first part of it is completely conventional neuroscience. If you went to the neuroscience meeting and you said that you didn't believe that people's thoughts and beliefs were encoded in an electrical state, everybody would turn and stare. This is completely conventional neuroscience at this point. No one's going to argue with you over that part, even though there are many questions about neuroscience and how that works. What you could lean on then is to say we already know that the inputs, meaning things you hear and things you read and the results of tests and all of that, are altering the electrical information in your brain. That's completely conventional. From there, there are known mechanisms by which that is also going to filter down to gene expression and tissues. You could stick to entirely known published work to make that link.
[15:10] Mayli Mertens: That's really good news. I tend to have audiences who are "I don't want it to just be philosophy." I want it to be usable for clinicians. And then the question becomes, how can I give practical examples of that? Unless they've already been done — practical examples of where a change in belief would result in a physiological change without getting my head shut off.
[15:47] Michael Levin: There are more flashy examples: there are papers on gene expression being changed by music, by meditation. But the far more conventional version is that if you sit there and deliberately focus your attention on things that stress you out, the world situation, whatever it is. You sit there, I'm going to take half an hour and I'm going to think of all the things that are freaking me out right now. If you do that, your cortisol is going to go up, your adrenaline is going to spike, all these physiological things are going to happen. That's either totally mysterious or completely non-mysterious, depending on how you understand neuroscience. This is not an exceptional human experience. This is an everyday thing. You get yourself all worked up. When you manage to activate your nervous system in a way that's causing stress and turning on cortisol, it is not controversial that at that point many cells are changing gene expression. They're being bathed in cortisol, your heart rate is going up, so cells are going to change their gene expression.
[17:01] Mayli Mertens: Enough to create a lasting, permanent physiological change.
[17:07] Michael Levin: Now, that's a slightly different thing. I'm not a clinician, but from my reading of neuroscience, and I think here you would have to talk to some clinical neuroscience people, there are thoughts that are persistent, meaning that, and obsessive, meaning that once you start thinking them, they sort of are hard to get rid of, and this we are writing something about a little bit of niche construction, where they're actually changing your brain slowly over time to make it easier for those thoughts to keep recurring. So if you talk to people who study depressed brains and how they got there, there are multiple. There's the version where you have some mutation that gives you a serotonin imbalance. We're not talking about that. We're talking about people who have acquired the various pathological states because of modes of thinking, because of things they've experienced in the environment, abuse and stress, and it doesn't have to be physical abuse. There's a huge literature on this. So all of that exists, and all of that certainly has long-term implications that, of course, include gene expression. You said something else before that, which is much harder, which is how do I give people a practical, "now with this knowledge, here's what you can do" therapeutically. That's hard. I don't think you should expect to be able to do that by yourself. I think there are many people working on this in labs, but together with them, the philosophical perspective that you bring could actually be incredibly useful. The standard version is just to lean into neuroscience and say that, yes, we know these things are all electrical in nature. Of course, it changes gene expression as every physiologist knows. There's a less conventional version of this, where you can actually point out that gene expression is fine, but there are many things that are driven by other layers of biological regulation that have nothing to do with genetics. That's a whole other huge battle. I don't know that you want to fight both of those at once, but certainly...
[19:26] Mayli Mertens: I do. I think I'm already done with the genetics part. One of my concrete questions would be the stuff that you're doing with bioelectric interventions that cause the planaria to have two heads or cancer to stop behaving like cancer. For example, if we talk about natural remissions in cancer, would there be a possible relationship between your beliefs, your cognition, and the bioelectric "cognitive glue," such that changing those beliefs can have physiological effects that create the kind of interventions that you're doing in your life. That's much more what I'm interested in.
[20:33] Michael Levin: I want to be really careful here. What I am not claiming is that right now, today, we have actionable protocols where somebody can, with the power of positive thinking, get rid of their cancer. I want to be very clear that we do not have this today. I'm not saying there haven't been examples of this, but by and large, you cannot count on something like that working. You need to get proper treatment. Looking into the future, I do think that the biomedicine of the future is basically going to be this. It's basically going to be taking what we already know happens, that various kinds of thinking change the way ions move across your muscle membranes. There has got to be a way to capitalize on that system, which is already in the body, to make the same thing happen in other cells that are not muscles. Once you can do that, the path to recapitulating what we do externally, which is to use drugs and other things that will hyperpolarize, for example, nascent cancer cells and cause them to normalize, seems perfectly plausible to me as a future research goal. And in fact, that's exactly what we're working on. I don't think it exists yet.
[21:52] Mayli Mertens: No, but I do think it exists naturally in a sense. If this hypothesis is true, if you can prove it, that could explain natural remission right now. I'm not saying positive thinking. There are people who make extreme big identity shifts. Just because they've been given shorter time to live, they make different choices. They change their entire behavior, and their behavior has been changed by something fundamentally shifting in their brain.
[22:22] Michael Levin: But what I don't know is whether the number of people that have experienced remission because of that is less or greater than the number of people who forego traditional therapies to go to some sort of alternative thing. They really believe that it's going to work. They end up dying of it, not because the conventional approach is much more effective; at least in cancer, it's not. The point is that aspect of it is probably real, but entirely unreliable at this point. You don't know when it's going to happen or how to make it happen. I'm not saying it's not real. I'm just pointing out that you can't really trust it yet. We are working to understand it so that we can make it work like Tylenol. When you take a Tylenol, mostly your headache goes away and you can count on it every single time. That is how we want it to work. We don't want this to be some mysterious thing. I'm not saying we are mechanical machines when everything's going to work like a calculator. That isn't it. But it has to be reliable. It has to be that people can count on it because we understand how it works. The other thing I want to come back to is your point about whether we see the world despite or because of our beliefs. There's a lot of work on this in terms of active inference around people like Karl Friston and Don Hoffman, and lots of neuroscience going back many decades to understand how we organize our world. I think the one thing we can say is that what we perceive is an extremely narrow slice of reality.
[24:13] Mayli Mertens: I don't think it's a slice. I think it's more like an interpretation of a slice.
[24:19] Michael Levin: We are perceiving a small slice and we are turning it into a model of the world that facilitates our doing certain things good enough to survive, which is mostly what evolution cares about, and keeps us from doing and seeing lots of other things.
[24:40] Mayli Mertens: It's not completely dependent on the senses we have. We have a spectrum that we see, we have a spectrum we hear, but it's so small.
[24:49] Michael Levin: There's the actual receptors that we have and what can we actually detect of the outside world. But then there's the cognitive architecture that we have. How do we put those stimuli together into some picture of what the heck's going on? We have lots of very strong assumptions about space, about time, about what makes for agency and things like that. And all of that gives us a very particular picture of the world.
[25:19] Mayli Mertens: I think that's why I run into so many problems because I don't share those. I want to ask you three more practical things. One, you said I don't have to do this alone. I've been very lucky with the sciences I've been working on, but a lot of geneticists and epigeneticists were like, we can't help you here because we have no explanation for this. I think the work of your lab and Ellie Crum from Stanford, who works on placebos and is a student of Ellen ******, would be great to work with. I told myself I wasn't going to apply for another grant, but if I can chase this idea and work with people in your lab or people doing empirical work in the mind and body lab who are used to testing placebo effects, that would be great. They did a study where they were studying the placebo and epigenetics. If I could write up this first, more conventional paper, it would be great if I could send it to you or someone in your team to either review it or co-author. There's another thing I'm working on with a gynecologist who works in reproductive clinics; she's in Japan. We've been working on a paper where we see self-fulfilling and self-defeating prophecies in implantations of abnormal embryos. I think your work explains it perfectly in the sense that we don't see how all these abnormal things in vivo are being solved by themselves. I'd really like to talk to you. Finally, I have a personal question. So what's the craziest idea you've had in the last six months? I'm not talking about conventional crazy, but where you have a thought and your next thought is, "Am I really thinking this?" and then you have no way of denying or dismissing it for being false because you don't have proof.
[28:01] Michael Levin: I apologize. I've got a minute before I'm going to get pulled off of this to the next meeting. On the first stuff, at this point, I don't make a very good co-author because I'm sitting on about 150 open manuscripts that I'm trying to write. We will both be old and gray by the time I write anything. I encourage you to find other people. You might reach out to Fabrizio, Benedetti, and there are many other people, but I'm happy to look at things and talk to you and provide advice if I can. I'm just not a great co-author right now. So that's the first thing. With respect to the crazy ideas. For me, I have a lot of crazy ideas; most of them I never talk about. The reason I have a simple criterion, all I want to know is, is this idea—crazy or not crazy is a bad classification. I think what's a good classification is, can this idea be baked to the point where it can actually help do something new? People send me all this stuff about God and the universe. My question is always the same. That's all great. What are you going to do with this to move forward? Okay, what is the next step that this lets you do that you otherwise couldn't do? Some of my wildest ideas, what I spend all my day thinking about is how do I turn this into something practical. If it can be turned into—I don't mean a widget that we're going to sell; I mean a way to move knowledge forward. If we can turn it into something useful, then I don't care how divergent it is from anything that's been done before. If I can't, then I'm probably not going to pursue it no matter how pleasing it might be to me because it's not going to do anybody any good.
