#179 Classic episode – Randy Nesse on why evolution left us so vulnerable to depression and anxiety

Summary

80,000 Hours Podcast - Episode #179 Summary

Classic episode: Randy Nesse on why evolution left us so vulnerable to depression and anxiety
Originally aired: February 3, 2026
Host(s): Rob Wiblin, Luisa Rodriguez
Guest: Dr. Randolph (Randy) Nesse

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Episode Overview

This episode revisits a classic conversation with Dr. Randolph Nesse, a pioneer in evolutionary psychiatry, about why our evolutionary history left humans so susceptible to depression, anxiety, and other forms of mental suffering. The hosts and Nesse break down evolutionary approaches to psychiatry and mental health, discussing how understanding natural selection's trade-offs can illuminate the origins, functions, and dysfunctions of our psychological responses.

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Key Themes and Takeaways

1. The Evolutionary Lens on Mental Health (00:55–06:11)

• Core insight: Before asking, “Why do we get depression or anxiety?” we must ask why evolution gave us the capacity for sadness, stress, and worry.
• Nesse argues that many psychiatric symptoms are not diseases, but evolved systems (e.g., pain, anxiety, sadness) that serve useful—albeit sometimes misfiring—functions.
• The traditional medical model’s limitations are illustrated, and Nesse calls for closer integration of evolutionary biology into psychiatry.

Quote:

“Why is it that so many people suffer so much uselessly?... We've got to understand how the whole system was shaped.”
— Randolph Nesse (09:02)

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2. Emotions as Adaptive Control Systems (13:54–18:31)

• Emotions are not just arbitrary syndromes but are suites of responses to recurring evolutionarily significant situations.
• Anxiety is adaptive in circumstances where you might lose something but could prevent the loss with timely action. However, there are many types of anxieties because losses come in many forms.

Quote:

“Anxiety is basically pursuing the goal of not losing something. After you lose something, there's another emotion that kicks up—that's called sadness.”
— Randolph Nesse (18:31)

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3. The "Smoke Alarm Principle" and Overactive Anxiety (24:06–29:22)

• Our anxiety systems are set up to err heavily on the side of false positives due to the immense evolutionary cost of false negatives (e.g., not fleeing from real danger).
• Most people’s anxiety feels disproportionate to actual threats, but from a gene’s perspective, this is the optimal trade-off (the smoke alarm that goes off for burnt toast, not just for real fires).

Quote:

“These systems are shaped to give off many, many false alarms... it's like a smoke detector going off; it's just like burning the toast.”
— Randolph Nesse (27:08)

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4. Sensitization, Vicious Cycles, and Therapy (33:28–41:22)

• Anxiety thresholds are regulated by experience—repeated traumas or panic can lower thresholds, causing spirals into panic disorder or agoraphobia.
• Exposure therapy helps reset thresholds by breaking the feedback loop of anxiety about anxiety.
• Medications should be understood as helping recalibrate alarm thresholds, not just “covering up” symptoms.

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5. Depression and Low Mood: Adaptive Pullback or Malfunction? (49:46–67:02)

• Distinction is drawn between sadness (response to loss) and depression (response to perceived unattainable goals).
• Low mood, Nesse argues, evolved as an effort regulation system—when efforts at a goal repeatedly fail, low mood pushes us to conserve resources and reassess.
• Modern environments may amplify this system, enabling us to become stuck in depression when we can isolate ourselves and ruminate.

Quote:

“People who keep pursuing unreachable goals spiral into worse and worse depression... once they give up, their depression goes away.”
— Randolph Nesse (60:18)

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6. Multiple Pathways to Depression

• Depression can arise from pursuing unattainable goals, from infections (sickness behavior), from heritable "brain diseases," or from positive feedback cycles similar to anxiety disorders.
• There likely isn't a single cause or type of depression.

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7. The Case Against Cynical "Selfish Gene" Interpretations (113:13–122:42)

• Nesse challenges the view that evolutionary psychology only explains cynical self-serving motives. Morality, guilt, and even guilt about tiny social slights are themselves adaptive traits selected for their benefits to social cohesion and genuine relationships.
• "Partner choice" in social and mating relationships selects for morality and loyalty—not just Machiavellian cunning.

Quote:

“Isn't it wonderful that we're not like chimpanzees? We really have capacities for genuine morality and love and friendship. It's astounding. And nothing about selfish gene theory makes that untrue.”
— Randolph Nesse (116:28)

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8. The Problem of Big Goals and Modern Striving (145:12–155:06)

• Discussion of why so many modern people—especially in Western countries—experience low mood from striving for large, often unattainable goals.
• While meaning is often derived from pursuing grand ambitions, the same tendencies can set many people up for disappointment and chronic dissatisfaction.

Quote:

“I love the motto carved in stone on a prep school... ‘Aim high, but not too high.’”
— Randolph Nesse (147:46)

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9. The Evolution of Aging (165:16–170:05)

• Traditional reasoning that organisms age because "machines break down" is challenged: many species can replace body parts indefinitely.
• Aging persists partly due to antagonistic pleiotropy—genes that are beneficial early in life but harmful later persist because they boost reproduction.
• Selection maximizes gene transmission early, even if it means later breakdown.

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Notable Quotes & Timestamps

• Why do we have so much social anxiety and guilt?

  “Because having that moral sense really is very important... taking a step back and looking at how natural selection shapes our capacities for morality and loving relationships, I think is the antidote.”
  — Randolph Nesse (00:00)

• On the fallibility of evolutionary psychiatry:

  “You can't be for or against evolutionary psychiatry. It's just using a basic science, however we possibly can, to better understand why we're vulnerable to mental disorders.”
  — Randolph Nesse (139:52)

• On striving and meaning:

  “People strive for meaning...meaning comes from having some goal that's larger than ourselves...even if you never accomplish it.”
  — Randolph Nesse (157:45)

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Essential Timestamps

| Timestamp | Topic | |-----------|-------| | 00:00–06:11 | Why evolutionary psychiatry offers a different approach to mental health | | 13:54–18:31 | Adaptive role of emotions and why we have anxiety | | 24:06–29:22 | Smoke alarm principle and the “false alarm” nature of anxiety | | 33:28–41:22 | Feedback cycles in anxiety disorders and effective therapy approaches | | 49:46–67:02 | Adaptive and maladaptive depression; effort regulation hypothesis | | 113:13–122:42 | Evolutionary lens on morality, guilt, and love | | 145:12–155:06 | The dangers and meaning of striving for ambitious goals | | 165:16–170:05 | Why do we age? Evolutionary theory of aging |

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Memorable Moments

• The Professional Daredevil (22:00): A motorcycle racer asks for medication to suppress life-saving anxiety before extremely dangerous races; Nesse refuses, emphasizing anxiety’s evolutionary protective value.
• The Smoke Alarm Analogy (27:08): Explaining why anxiety overreacts—better to have “999 false alarms than one missed real fire.”
• Case Study – Loss and Depression (60:18): Women pursuing childbirth via IVF experience spiraling depression; symptoms resolve when they relinquish an unreachable goal.

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Episode Tone & Style

The conversation is in-depth, engaging, and witty, featuring thoughtful clinical anecdotes and a balance between clear scientific reasoning and personal reflection. Both host and guest are unafraid to question standard dogma or highlight lingering mysteries and unanswered questions.

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Overall Summary

This episode offers an intellectual deep-dive into evolutionary psychiatry: why our emotions function the way they do, why mental suffering is so common, and how a more nuanced, evolution-informed understanding can improve both science and self-knowledge. It challenges both oversimplified medical and evolutionary models, suggests new ways of thinking about anxiety and depression, and even brings fresh perspective to classic Freudian psychoanalysis and the origins of human morality.

For those interested in applying these ideas to their lives or to public health, Nesse’s core message is that suffering—from anxiety, depression, even the pain of striving—often isn’t a malfunction, but the result of evolutionary trade-offs. Seeing mental health this way can reduce stigma, open new paths to therapy, and foster more empathy for oneself and others.

Transcript

[Randolph Nesse]

Why do people have so much social anxiety? Because being very sensitive is generally a good thing for your genes, if not necessarily for you. And why do people have so much guilt and worry so much they might have accidentally offended somebody? Because having that moral sense really is very important. People who don't have that moral sense don't have very many friends, or at least their friends are just friends who want to get something and trade favors instead of friends who will actually care for them when they really need help. I think a big reason why evolutionary psychology hasn't caught on more is because a lot of people have a simplistic version of selfish gene theory, and they think it implies cynicism and it implies everybody's just out to have as much sex as they can. But taking a step back and looking at how natural selection shapes our capacities for morality and loving relationships, I think is the antidote that can make all of this grow in a healthy way.

[Rob Wiblin]

Hey, everyone. Welcome back to our next holiday classic episode. This one with evolutionary psychiatrist Randy Nesse is among the episodes that listeners most often tell me really either blew their minds or helped them somehow in their in their personal life. The core insight that Randy has is a relatively simple one. Before asking why we get depression or anxiety, we first have to ask why we have the capacity for feeling sad or stressing and worrying about things at all. What did evolution actually give us these systems for in the first place? And once you start thinking that way, a lot of other ideas naturally begin to click into place. For instance, Randi's smoke alarm principle explains why anxiety so often feels very disproportionate to the actual threat that we're dealing with. It's because the cost of a false positive is, in most of these cases, a lot lower than the cost of a false negative. He also explains low mood as a system for regulating effort. When things are going well, when we're getting a lot of reward, our positive mood pushes us to invest more into our pursuits, to get up early in the morning and go to bed late at night and really burn the candle at both ends trying to get that reward. Conversely, when things aren't paying off and it's not obvious how we're going to succeed, low mood gives us a nudge towards backing off and not potentially wasting or expending effort on stuff that isn't going to work out. And that approach isn't just armchair theorising, as you might worry, because it does generate testable predictions about when people should get depressed or feel particularly anxious and what potentially should be able to help snap them out of it. Randi, in this episode separately provides a partial defence of Freudian psychoanalysis, which is not something I'm generally that partial to myself. And he also gives us, I think, the standard correct but remarkable evolutionary explanation for why it is that we age and die at the time in our life that we do. So I think it's a fantastic episode that I'm very happy to be re releasing now. So without further ado, I bring you Randy Nesse on why evolution has left us so damn vulnerable to mental illness. Today I'm speaking with Dr. Randolph Nesse. Randy is a leader in the field of evolutionary psychiatry, that is the application of evolutionary thinking to understanding how it is that we can be as vulnerable as we are to mental health problems and thereby to improve their treatment. He came to that after helping to put evolutionary medicine, the use of evolutionary theory to understand health and disease more broadly on the map. Nesse had a 40 year career as a professor of psychiatry at the University of Michigan before moving to Arizona State University to found the center for Evolution and Medicine and the International Society for Evolution, Medicine and public health. In 2019 he published the very popular book Good Reasons for Bad Insights from the Frontier of Evolutionary Psychology, which I very much enjoyed and I know a number of other people did as well. In addition to being a clinician who has treated many hundreds of patients through his career, he's also the author of hundreds of published papers, book chapters and talks on psychiatry and evolution which have clocked up a ridiculous number of citations. Thanks so much for coming on the podcast, Randy.

[Randolph Nesse]

I really appreciate the opportunity, Rob. I look forward to the conversation.

[Rob Wiblin]

I hope to talk about how to collect evidence for and against evolutionary hypotheses and how people might be able to make the world a better place using evolutionary medicine. But first it was your exasperation with the intellectual foundations of psychiatry that caused you to help get the entire discipline of evolutionary medic and off the ground. Can you explain what is missing in the way that we approach psychiatry in the 70s and I guess to a great extent how we still approach psychiatry today.

[Randolph Nesse]

So I started my career in 1974 when the DSM was just getting going and psychiatry was in the midst of its giant transition from mostly psychoanalytical to mostly biological. And it was so interesting at the time. Everybody was fighting at every grand rounds trying to have this global picture of how do we think about these kinds of problems. And most of my friends were going into either psychoanalysis or drug treatment or neuroscience or behavioral work And I really wanted to find some broader way of using everything we know. To use every possible treatment for patients. And I was very frustrated. I mean, you could call yourself an eclectic psychiatrist, but that's kind of insipid. And you can't possibly stay in an academic department doing eclectic psychiatry. So I found my way over to the Museum of Natural History. Where there were these biologists who study behavior full time. And they were appalled that psychiatry wasn't already based on evolutionary biology.

[Rob Wiblin]

Yeah. So I guess what approach were people taking then? And kind of in what sense was it quite a mess?

[Randolph Nesse]

I mean, everybody was just fighting. I mean, the psychoanalysts were quite confident that early life experiences and unconscious defenses. Were responsible for most mental disorders. And the biological types at that time. Were quite convinced that they would be able to find specific genes, specific brain loci and abnormalities. To make psychiatry like the rest of medicine. Ever since then, my theme has been to show that an evolutionary approach. Can make psychiatry really much more like the rest of medicine. And that currently, what's called the medical model in psychiatry. Really isn't very medical at all.

[Rob Wiblin]

Yeah. How would an evolutionary lens on mental health. Will change how you would approach psychiatry. And how you would conceptualize and structure. Your understanding of mental health problems?

[Randolph Nesse]

So that's the topic of our whole conversation. So there's lots to say about that. But just to summarize where we're going, going, possibly Rob. I mean, the first thing is a really medical approach to psychiatry. Carefully separates symptoms from diseases. And right now, there's all kinds of arguments about how much depression is abnormal. And there's a vague idea that some might be normal. But without thinking about how the capacity for depression evolved and how it can be helpful. All those questions are just arguments instead of actually science. Another issue is trying to understand what causes disorders. And we kept hoping that there would be a whole bunch of very separate disorders. That we could define with the dsm. For those who don't know, that's the Diagnostic and Statistical Manual, Kind of the bible for diagnosis for psychiatry. We hoped that we could define specific disorders. And each one would have a specific brain cause. And if we could find the cause, then we could find better treatments. And I was on board with that. I mean, we all were. In fact, we thought the DSM was a temporary document. Until we could learn better about what the specific disorders were defined by brain problems. Just like Alzheimer's disease or cystic fibrosis or breast cancer. You define those things based on specific pathological and biochemical findings. And we hoped that we could find those in psychiatry, but we've been doing that for 30 years now, and it just hasn't worked. I still hope it works. I want to be very clear. I really, really hope we can find specific genes, specific brain pathways, specific neurotransmitter, abnormal maladies responsible for some of these terrible disorders. But so far it hasn't worked. And that means to me that we need to also step back and take a larger picture, to consider whether some of these disorders are more like other things in medicine, like heart disease, like congestive heart failure. Congestive heart failure is failure of a whole system which can have a dozen causes, and all those causes can interact. So if some mental disorders are more like these kinds of medical disorders, we need to be trying to understand how the systems all work and work together in order to understand. Understand why there are such problems.

[Rob Wiblin]

Yeah, I think that's one thing that wasn't so obvious to me before reading the book is how peculiar it is, how we define and kind of cluster mental health problems. So basically, you say that someone has depression if they have a set of symptoms that correspond with this kind of cluster that you call depression. But that's not how we think about respiratory illnesses. We don't say, someone comes in with cough, and you're like, okay, yes, you have cough, yes, you have fever. And then we say, okay, you have respiratory disease syndrome, and then leave it at that. But because we don't have a deep understanding of the mechanisms that are generating the symptoms, everything is just a syndrome. Or it seems like basically we just approach everything as just a cluster of symptoms, and then we imagine that that is a disease. But that's not really. That's not what we do in the rest of medicine.

[Randolph Nesse]

I don't think it's really such a dramatic difference, isn't it? Why is it that? The other thing is, I mean, depression is a symptom, not a disease. Except that usually it's useless. And this is what's so confusing, I think, is that if natural selection is so good, how come almost all low mood isn't useful? And for that matter, why do we all have, or at least all nice people have more anxiety than they need? There are a few people who don't have enough anxiety and they're kind of obnoxious. But it's fascinating. And these are evolutionary questions. I mean, this is the whole core of evolutionary medicine. Just to put this all in. I wrote my first article about evolutionary psychiatry in 1984, and it led me to ask this different Question. I saw all around me so many people suffering with so many different things. And I had to ask myself, who the hell designed this thing? Why is it, why is it that so many people suffer so much uselessly? I mean, is it, are we in a sick society? Is there some toxin in the water? Is it, you know, we just have bad genesis? And that led to thinking about evolution and realizing that we've got to understand how the whole system was shaped. And that led to me realizing that there's no way I'm going to make progress about trying to understand mental disorders from this point of view until we first understand why natural selection didn't better protect us from all kinds of medical disorders. That led to work with the great biologist George Williams and created the field of evolutionary medicine that's now going very strong.

[Rob Wiblin]

Yeah, we'll come back to that in just a moment. But in the book, you have this crazy anecdote about going to a psychiatry conference and asking everyone there what they thought moods were for and just getting back completely bananas responses. I mean, just to give some quotes from the book on this. So you asked a bunch of psychiatrists at lunch why the capacity for low mood existed. And some of the answers you got back were, depression is what makes us human. Depression is essential for relationships to be meaningful. I never even thought of that. Does there have to be a reason why we have a capability for low mood? Depression is a brain disorder. There's nothing useful about it. I think it's as people come to see, that's a very different, very different perspective on things than what we're about to do.

[Randolph Nesse]

If you ask the same doctors. So what's cough for? They say, oh, well, cough is to clear bad stuff from your respiratory tract if you go. Or vomiting. Vomiting is to clear poisons out of your GI tract. If you ask them what's fever for, it gets more on the edge. I mean, most doctors realize that fever is a useful response to help combat.

[Rob Wiblin]

Infection or sometimes useful response.

[Randolph Nesse]

Yeah, but not everybody gets that. Always. That's kind of on the edge. If you ask about pain. I think where I really started getting going on this, Rob is in neurology studying pain. And we saw a patient who had no capacity for pain and he was a wreck, he was a smoker and his fingers were burned right down to the bone because he didn't know. And that reminded me of a kid that I had known in junior high school and he too had the same syndrome. It's extremely rare, one out of several hundred thousand people. And why Is it rare? Because most people with that syndrome are dead by the time the age of 30 or 40. Pain itself is useful. When you're experiencing pain, it means something's wrong, you better change things. But this made me start thinking differently about all these responses that natural selection has shaped for us. And it made me think, gosh, if physical pain is so useful, what about mental pain? And that's really the foundation for a lot of evolutionary psychiatry.

[Rob Wiblin]

Okay, let's push on to the meat of the conversation, which is your book, Good Reasons for Bad Feelings, which might be my favorite book that I've read this year.

[Randolph Nesse]

Oh, I'm reading to hear that. How thrilling to hear that you read lots of books.

[Rob Wiblin]

Yes, yeah, I do. I read like one or two a week. So I guess that is pretty strong praise. Yeah. And rereading it recently, I realized just how much there is in this one. There's kind of a lot of stuff, subtle interlocking ideas. And I realise that we're not going to be able to impart the full picture, the full way of thinking that comes through in the book, in this conversation, because even if it's a very long conversation, it just won't be quite enough. And some topics I don't think we're going to get to at all, including eating disorders and drug addiction.

[Randolph Nesse]

Let's talk about eating disorders. That's important.

[Rob Wiblin]

Okay.

[Randolph Nesse]

Yeah.

[Rob Wiblin]

All right. Okay, we'll do that one quickly. There's also grief at the death of a loved one. Bad sex, bipolar disorder we might get to quickly, but there's a lot more on it. So if someone enjoys this conversation, they really should go and enjoy the full book. But, yeah, a key part of the book is setting out to apply evolutionary thinking to each of the key mental health symptoms or syndromes that people are most familiar with. And I guess I'd like to start by handling one of the relatively more straightforward cases so people can get a better sense of what an evolutionary explanation for a psychological trait can look like. So what is the evolutionary origin of our capacity for anxiety?

[Randolph Nesse]

You know, I experienced plenty of anxiety myself, and I had the privilege of helping to develop one of the world's first research clinics on anxiety at the University of Michigan. My first research was with George Curtis, and we were looking at how neuroendocrine changes happened when you bring a snake into the room with someone with a snake phobia to treat them. It's very effective, safe treatment and a remarkable opportunity to look at how the body changes in response to anxiety. And during those years Treating people with anxiety disorders. After a few years, I realized, gosh, I'm treating emotions full time. What are emotions for? So I'm gonna back us up just one stage. Rob, instead of talking about anxiety overall, we should talk a little bit about emotions. I asked myself, so, gosh, anxiety is one emotion. There's a bunch of emotions. Why do they exist at all? And I went reading in my psychiatry textbook, and the entire chapter on emotions was one and a half pages. That's interesting. I mean, if you study heart disease and you look up in a medical textbook about heart disease, you know, there's 100 pages about how the heart works and how the different parts are for. So then I went looking at emotions research, and I spent a full year just reading about emotions. And I pretty much gave up at the end of that. And I thought, you know, everybody's arguing about how many emotions there are and what each emotion is for, and there's no agreement. And I really was very frustrated. And then I went back and found what William James had to say about it. You know, William James is a great psychologist. He essentially said, I'd as rather read the literature on emotions again as catalog rocks on a New Hampshire farm. There was no order. There's no categories. There's no way of making sense of it. And I thought, well, if he can be frustrated, I can be frustrated too. So I looked at evolutionary approaches, and most of them were saying, what's the function of anger? What's the function of anxiety? What's the function of depression? And I asked myself, well, how do these emotions come to be? And the answer is that they're suites of coordinated responses that change lots of things, physiologically and cognitively and behaviorally to cope with a particular kind of situation that's recurred over evolutionary time. So people who felt the hot breath of a tiger on their shoulder, and the a lion is salivating in front of them, who experience the emotion of awe, those genes didn't stick around at all. They became lion lunch. While people who had this coordinated response that we call a panic attack or a fight flight reaction, where they start sweating and they run really fast and they breathe really fast, and their heart pounds and their muscles get tight, those people were more likely to survive. And so natural selection shaped a very specialized emergency response we call a panic attack. And all of a sudden, with that insight, which I'd never quite had before, I realized, gosh, every emotion needs to be understood not in terms of its function, which was the prevailing evolutionary view. And the still continuing evolutionary view by many people. But instead, in what situation is this emotion useful? Or was it useful for our ancestors? And this also solved one of the biggest conundrums about emotion research. Are the emotions separate little entities or are they all overlapping on dimensions? No, you think about this from an evolutionary viewpoint, and they're like overlapping boughs on a tree because they all evolve from each other. So this made sense of emotions. Now we can go into anxiety. But that's what made it possible for me to think about it, Rob, and I'll try to answer my own question, then we can go on. So the question is, in what situation is anxiety useful? And the answer to that is fairly. In situations where you're in danger of losing something, it's good to have a special mode of operation that alerts you to the possible loss, where you can take preventive action and avoid that situation in the future. And the next thing that happens is, hey, is there only one kind of loss? No. You can lose your finger, you can lose your friend, you can lose your mate's fidelity, you can lose your money, you can lose your health, you can fall off a building. And this helps to explain why there's so many different kinds of anxiety. Natural selection is gradually and only partially differentiated kinds of anxiety to cope with those different kinds of possible losses.

[Rob Wiblin]

So an alternative way that we could frame the question is just in what circumstance is anxiety useful? And basically, it's in a circumstance where you might lose something, but if you take a response, then you might be able to avoid losing something. Is that how you would summarize it in one sentence?

[Randolph Nesse]

That's exactly right. And while we're at it, a lot of my work is trying to understand human behavior in terms of the goals we pursue. And anxiety is basically pursuing the goal of not losing something. After you lose something, there's another emotion that kicks up that's called sadness. A lot of people confuse sadness with depression. I think they're very different from an evolutionary viewpoint. Sadness is when you lose something, and if you just have lost it and there's no getting it back, then you feel bad for a while and it all goes away. On the other hand, if you continue to pursue some unreachable goal, that's not sadness, that's low mood, and that can escalate into depression. But let's say that. Let's do lots more about anxiety first.

[Rob Wiblin]

Yeah, yeah, we'll come back to depression, because I think it's a somewhat more complicated case, Sarah.

[Randolph Nesse]

Much more. Much more.

[Rob Wiblin]

Yeah, yeah. Okay. So We've got a situation in which anxiety is useful. And you pointed out in the book that obviously people come into the psychiatrist office saying, I have high anxiety, I feel anxious all the time. This is ruining my life. Not many people come into the psychiatrist's office saying, I never get anxious, I never feel anxiety about anything at all. But those people have a lot of problems, too. They don't come into the psychiatrist's office, but they end up in the emergency room because they've been in a car crash or they end up getting fired because they just said what was on their mind when really they should have had prudence might have been the better part of valor in that workplace meeting. So there's kind of hypo anxiety. Thinking about it this way allows you to have this structure in your mind where you can see missing mental health problems that should be there and indeed actually are there, but aren't necessarily being recognized because people don't dislike them in the immediate sense.

[Randolph Nesse]

And it's so useful to talk to patients about that. Rob, if you talk to people say, gosh, you have way too much anxiety and it's wrecking your life. But there's something that would be worse, having no anxiety. And all of the patients say, no, what? There's something good about me. There's something good about my reactions. They say, yeah, you're protected against a lot of kinds of dangers and problems that people who have no anxiety don't have to deal with. So this came to me from a medical approach. Again, what about people who don't have enough cough? And there are a lot of people like that. Older people very often do not cough very easily. And what happens to them? They get pneumonia and die. Because if you have surgery, very often the nurses and doctors will say, you've got to blow into this tube and make yourself cough a lot. And that's because you've got to clear all that gunk out of your lungs. Otherwise it's going to be a fertile breeding ground for bacteria to cause pneumonia. Likewise, vomiting at every university, sadly and especially at University of Michigan, every year some poor undergraduate comes into the emergency room dead on their 21st birthday. Why? It's because some fraternity or something said, ah, you get to drink a whole quart of vodka tonight because it's your 21st birthday. And for most people, they just vomit and they get very sick. But if someone's vomiting reflex isn't working right, they die. And now we go back to anxiety. If you don't have enough anxiety, that can be fatal. We coined the term hypophobia. I had the great privilege of working with the psychiatrist Isaac Marks in London. We wrote an article called Fear and Fitness in 1990 that people still read a lot. And in that article, we coined the term hypophobia to describe this serious mental disorder that never comes to psychiatrists tension. And we even joked about giving people drugs that would increase their anxiety to save their lives. Except it's very hard to get people to take medications like that.

[Rob Wiblin]

It's not a great business plan. You have this amazing story in the book of a professional daredevil who came into your office saying, I have to compete in this daredevil competition. And every time I do, I just throw up from fear the night before. And you're saying, well, how many people die each year in these things? I'm like, oh, it's about 10% of the people who participate die every year. Can you give me something, doctor, just so I don't feel this high level of anxiety? And I think you sent him home saying that that would be inappropriate under the circumstances.

[Randolph Nesse]

Well, you know, and this is a great example, Rob, of how clinical judgment is difficult and there are often no simple, easy answers. That person was actually a professional motorcycle racer. And. And he had one friend who got killed and another friend who became paralyzed from the neck down. And he had had an accident where he was thrown off his bike. And he said, I'm not scared, but I do vomit, and I can't drink enough. And going into races, I'm dehydrated, and it's dangerous for me. You've got to give me something to make me less anxious. It'll be good for my health. And I sympathized with him because he was doing big promotions and his whole income depended on, you know, being the winner in these motorcycle race competitions. So we had long conversations, and I said, I'm sorry, I don't want to give you medication for this. I think, you know, this is a case where anxiety is trying to save your life. He left quite angry, and maybe he was right, and he might well have gone to someone else. But these are difficult decisions.

[Rob Wiblin]

Yeah. Yeah. Okay. So we've got a sense of when maybe a typical level of anxiety is helpful, and I think people could probably appreciate that. But maybe the weird thing about anxiety is that so many people do just feel anxious all the time. It's really a remarkable fraction of people for whom the majority of their mental life is thinking up things that could go wrong, like pretty unlikely things that could go wrong. And then feeling bad about it. Why might we expect that people would have such a seemingly overactive and over eager sense of anxiety from an evolutionary point of view?

[Randolph Nesse]

Again, if you just think about this in terms of brain mechanisms, you can talk about the locus coeruleus, a little blue spot in the brain that influences how much your anxiety goes off. But when you think about how natural selection shaped those mechanisms in that little blue spot in the brain, you have to ask, what are the costs and benefits of the anxiety threshold? The sensitivity of that system being cranked up so it goes off for anything, or cranked down so it hardly ever goes off. And that took me to thinking about what's called signal detection theory. Signal detection theory is the same thing that electrical engineers use when they try to decide whether a click coming across a wire is an actual signal or just noise getting us to the signal noise ratio that we talked about a minute ago as we were figuring out the microphone setups. Likewise, if you're running a radar setup and looking to see if those blips on your radar are Soviet missiles coming across the North Pole or a flock of geese, you had better be really, really sure that it's a flock of missiles, not geese. So you set the threshold for that to be a really, really, really high threshold for saying it's rockets. Because making the wrong decision could end the entire world as we know it. On the other hand, what about if you're in a situation walking down a dark street? The chances you're actually going to get mugged might be 1%. The cost of doing things to avoid that might be spending about 20 or 30 calories to go out of your way. The cost of not protecting yourself might be really time in the hospital and sickness and loss. And put it more into an ancestral setting and you might remember for the book, I actually put some numbers on this. Imagine you're getting water for your family at the watering hole on the savanna and it's evening and you hear a noise behind a rock. Noise is about like this. Grr. It's not. If it was grr, then you're going to run like hell because it's a lion. If it's gr, that's not a lion, you're pretty sure. But if it's just grr, you can't tell. So how loud does the noise need to be for you to run? Well, pretend that the cost of running is 100 calories and pretend that the cost of not. And you always get away free. And pretend that if you don't run you are eaten by the lion. And that's about 100,000 calories. The ratio is about 1,000 to 1. Whoa. So that means that anytime the loudest noise is loud enough to indicate the probability of a lion is there greater than one in a thousand, you should run. And that means. And when I first did this calculation, Rob, I couldn't believe my paper. That means that 999 times a normal reaction will be a false alarm. This helped me help my patients. I was seeing patients. I'd take them to the grocery store, and I'd say, we've been here four times now to the grocery store. Nothing bad has happened. You felt anxious, but there's nothing dangerous here. And I felt like saying to them, why are you still so anxious? You know, there's nothing dangerous here. And they say, I don't know, Doctor. I just feel the anxiety. But after I realized how the system was shaped by natural selection, I started instead saying, you know what? These systems are shaped to give off many, many false alarms. And you're also reacting to your own anxiety. It was a positive feedback process where thinking that something might be coming, thinking that you're afraid of your own anxiety symptoms, like shortness of breath is spiraling it all up. And that helped my patients just enormously. Instead of feeling like I'm a defective person with a brain disease, they started saying, gosh, it's like a smoke detector going off. It's just like burning the toast. And I want my smoke detector to have false alarms because I want to make really sure that if there's ever a real fire, it goes off for sure.

[Rob Wiblin]

Yeah. So the smoke alarm principle is a really good name for this because it's just so relatable. I would say our smoke alarm in our house goes off every couple of days, basically, and has since we moved in, almost. Well, every single time so far, just because we've been cooking. But have we gone and said we're going to get a new smoke alarm because we don't want a smoke alarm that will go off at that level of smoke? No, because while it is kind of irritating to have the smoke alarm go off, I just push it and it stops running. Whereas if it didn't go off sufficiently quickly and there was a fire, that would be an absolute catastrophe for the entire apartment building.

[Randolph Nesse]

So I'm going to pause here for a second. You should get a new smoke alarm, because the key for a really good system is that it detects on something. I'll call the curve. Exactly what optimum threshold is to give you minimum false alarms and maximum responses when you need them. Newer smoker alarms are better at detecting the real fires and not detecting false alarms. Likewise. That's our goal with our patients. We're not just trying to down regulate anxiety. We're trying to rewire the brain with a combination of medications and behavior therapy and cognitive therapy and even other kinds of psychotherapy. Rewire the brain basically so that they appropriately detect real dangers and respond to them, but down regulate responses to things that aren't really that dangerous?

[Rob Wiblin]

Yeah. Okay, well, I didn't expect us to get fire safety advice, but maybe I will go get a new smoke alarm. Given that the technology evidently has advanced, maybe future generations won't be able to relate to the smoke alarm principle name anymore. But yeah, the underlying structure here is that from an evolutionary point of view, from the perspective of your genes, it's possible to lose everything in a moment. You can be killed, you can be killed by a lion, you can be killed by a fire, and then your evolutionary fitness just goes to zero right away. It's not easy to double your fitness. It's not easy to double the expected reproduction in your life in any way, in any given moment, in any given day. That basically almost never happens. So there's much bigger downsides than there are upsides to almost every decision that you make.

[Randolph Nesse]

Did you ever think that people really, really don't want to die? None of us really want to. We really, really, really don't want to die. Why is that? Gosh, there's a pretty straightforward answer that you've just given.

[Rob Wiblin]

Yeah, that one's not. I'm not sure whether to go down the rabbit hole, but there was this beautiful case of one of the funniest book reviews I've ever seen of a philosopher who tried to explain disgust, who tried to explain why it is that humans beings have a disgust reaction. And they went through this extraordinary philosophical thing that it's about ambiguity between death and life without any reference to evolution or without any reference to what function disgust might seem.

[Randolph Nesse]

Earth.

[Rob Wiblin]

And this person wrote this absolutely scathing, hilarious book review where they said, obviously it's to prevent disease. Obviously it's to prevent you from dying. Likewise, I can imagine a philosopher saying, like, why is it that we fear death? They're like, if you're a biologist, this is a very, very straightforward question.

[Randolph Nesse]

Right.

[Rob Wiblin]

Anyway, you're bringing it back to anxiety. So this argument seems extremely powerful. It's almost, I think, too powerful. I'm always worried that this would suggest that all of us should have an extreme level of anxiety. Right. And personally, I feel like the smoke alarm principle doesn't really describe my relationship with fear. I feel like I'm more like, I've never really had a panic attack. Sometimes I'm in situations that are a little bit dangerous, and I usually don't feel that concerned. Shouldn't I be some bizarre aberration that's highly dysfunctional? But it seems like there's at least a meaningful number of people who are like me. So how is it that we can explain normal levels of anxiety, given the smoker lamp in the.

[Randolph Nesse]

That's a good question, Rob. I mean, how come everybody doesn't have bad anxiety all the time? And I think it's because anxiety has costs as well as benefits. You know, I've talked with people who do podcasts who are so nervous that they might make a mistake on their podcast that they can't do it, or they're worried in the middle of their conversation that they'll just stop. In fact, I've treated hundreds of people with social anxiety. Let's go down that hole for just a second. Most people are nervous about speaking up in public, and they plan what they're going to say, and they sometimes don't listen to other people as they're thinking about what they're going to say, and then they say it and see what other people do. I think this is a very useful response because what other people think about us is so vastly important. And if you accidentally express some anger or hostility or criticism of somebody without really wanting to, that can be really bad for your social relationships. So I think social anxiety is very, very important, and most of us have a good dose of it. People that don't have much social anxiety at all are the people who just say stuff, you know, and they get in all kinds of social trouble, and their friends wonder, how come he doesn't like me today? And then they have to realize, no, this is just a person who doesn't get it, and they don't have social anxiety.

[Rob Wiblin]

Yeah. So the limiting factor is just that, spending much of your mental life worrying about things that could go wrong, it has big benef, because you might avoid getting killed. On the other hand, it's maybe absorbing resources that could be allocated to some other function more usefully and avoiding you from getting distracted from the things that.

[Randolph Nesse]

You'Re doing, stopping you from doing things that are useful and interesting. Yep, absolutely. But this brings up another thing, though, that natural selection has also shaped mechanisms that regulate the threshold, how easily anxiety goes off as a function of experience. And this can be good and it can be bad if three times in a row. I had one woman who, I mean, she was working in a grocery store in downtown Detroit and she'd been on her job for about two weeks and somebody came in and pointed a gun in her face and said, give me all the money in the cash register or I'll blow you away. And she fell apart, gave him the money, and decided she's never going back to work there. But that's what she knew how to do. And so she got a job in a suburb where she thought, she thought she'd be safer. Three weeks later, she's sitting there at her cash register on the night shift, because you get to start the night shift if you're a new employee and somebody comes in and points a gun at her and says, give me your money or you're dead. And that was it for her. We were supposed to treat her in the anxiety clinic and relieve her of her fear of working as a grocery store cashier. But her anxiety system had adjusted to the point where, you know, even being in a grocery store felt dangerous to her because in her experience, it was life threatening. Conversely, the way we work with people who are just going to the grocery store to buy their groceries and having fear, which is the classic symptom of agoraphobia, by the way, how do we help those people? Well, you have them go to the grocery store and stay there while they have their panic attack. And wait for the panic attack to go away, because it always will in half an hour at the most, usually. And doing that repeatedly essentially rewires the brain and makes that threshold go up so the panic doesn't come on as easily. And patients are amazed that it works because you have to get people to do something that seems very abnormal and painful to get over their anxiety. But this is a global general principle for coping with anxiety. If you want to down regulate your anxiety, you need to go and do the things that seem dangerous and let the anxiety happen. And if you do that, there's a built in mechanism that down regulates your anxiety.

[Rob Wiblin]

Yes. So in the book, you talk about this capacity that humans have for kind of sensitization with the moods or with the feelings that they have. And I think the way to understand that is to think. So your brain is trying to balance or it's trying to get an appropriate level of false positives. And the appropriate level of false positives varies depending on how likely a threat is to actually be there. If a Threat is extremely unlikely, then you don't need to panic as frequently, or you don't need to have a very anxious response as frequently. By contrast, if someone coming into the grocery store and pointing a gun at you is actually very common, then there's far more reason to be skittish and to allow a lot of false positives.

[Randolph Nesse]

Basically, well, here's a way of creating panic disorder or taking one panic attack and creating it into panic disorder. All you have to do is take your panic attack into an emergency room at a busy hospital and the doctor says to you, gosh, you're breathing fast and your heart is pounding like mad. There doesn't seem to be any sign of a heart attack or a stroke or a seizure or anything like that. But you should be very careful and watch for these symptoms. If they happen again, come back, whoa. All of a sudden, that well meaning doctor has transformed an ordinary fight flight response into a signal to the person that it could be a heart attack or a stroke or a seizure. And they should start watching for such symptoms. And then they go mow the lawn and their heart starts pounding and think, oh my God, maybe it's happening again. And guess what that does, that causes anxiety. And what does the anxiety do? The anxiety causes higher heart rate and more shortness of breath and more muscle tightness and more sweating and more anxiety. And this is called a vicious cycle. And so many mental disorders are products of vicious cycles, that is control systems that run out of control and escalate just like a snowball running downhill or a truck without brakes. And telling patients that that's what's going on doesn't solve it quickly, but it's really helpful. Previously I told people you have panic disorder. It's a product of your brain and your experiences, and we're gonna give you medications and have behavior therapy to help you out of it. And the patient said, but doctor, I know it's my heart. I can feel my heart pounding. It's not mental, it's my heart. And once I was able to tell them, no, your heart pounding fast as a part of a normal useful response to get you away out of life threatening danger. And that's a false alarm. I mean, that helps so many patients so much. This should be, I think, a routine part of treatment of people with panic disorders.

[Rob Wiblin]

Yes. So you talk about how this sensitization process, which is evolutionarily adaptive, we think, because the brain is kind of learning how threat filled the environment is based on how frequently you've had anxiety in the past. But Then that can create this runaway spiral where past anxiety causes more anxiety attacks, which then causes you to learn that the environment is more full of threats and on and on and on.

[Randolph Nesse]

A lot of anxiety is caused by anxiety, right? And people who have a public speaking fear sometimes get so frightened in the midst of their public speaking that they lose their train of thought or something like that, making them again fear the anxiety itself. So a lot of the worst anxiety is a vicious cycle caused by fear of anxiety.

[Rob Wiblin]

But that made me wonder, given that these systems are, at least with that design, very unstable and at risk of spiraling off in a very bad direction, shouldn't you also need to evolve some stabilization mechanism basically to short circuit that from ever happening? Because otherwise you do end up with someone who's just a person who's just hiding in the cave, unable to go out because they've ended up on the wrong end of one of the sensitization spirals.

[Randolph Nesse]

And in ancestral times, if you're hiding in that cave, you'll eventually get hungry and therefore you'll have to go out. There's no alternative. And then the normal systems will reallocate your effort and your anxiety threshold appropriately for your environment. In modern times, however, you can go in your room and shut the door and get someone to deliver your food and have agoraphobia so bad you never go out at all. We've seen patients, we had to go visit people at their homes because they had not left home in two years and they had medical problems that they had to go to the hospital, but they couldn't because every time they left their home, they'd have a panic attack. So one of the very best ways of dealing with these things is to use medications. And previously I told patients, you know, we're going to use these medications to calm down your panic attacks. It'll be very helpful. And they always said, I don't want to cover over my symptoms, doctor, I want to get to the root of it. But once we started saying, you know what, you're having false alarms on a useful system, and this system is going to turn those off and help your inner mind to realize that the environment is not so dangerous as you think, and stopping this runaway positive feedback cycle, then patients said, oh, that makes sense. And that would help them take their medications, would also help them realize if they had mild breakthrough symptoms, it wasn't anything to worry about. And it also helped them realize that they were likely to be able to stop their medication after a few months without everything coming back, because it wasn't just covering over the symptoms. It was essentially resetting the anxiety threshold to be more appropriate.

[Rob Wiblin]

Yeah. I'll just quickly note that in the book you talk about for extreme phobias that people have of specific things, exposure therapy is an extremely effective technique for treating those. So if there's someone in the audience who has an extreme phobia of dogs or whatever it might be, do go and pursue exposure therapy. Because it seems like that's one of the cases where you have a surprisingly high, almost complete cure rate of many of those things with the right treatment.

[Randolph Nesse]

But it's not that easy. I mean, you can tell people, oh, just go expose yourself.

[Rob Wiblin]

Just go do something incredibly scary.

[Randolph Nesse]

Yeah, yeah. I mean, most people need help and guidance in doing that.

[Rob Wiblin]

In the book, you make this great point that mood regulation is a more tricky business than it might first appear. Because for any access, like anxiety or anger or fear or sadness, it can fail in any one of. At least these were the ways that you mentioned. So you can have the baseline level being too low, baseline level being too high, the response to a stimulus being insufficient, the response to a stimulus being too much, the response being generated to things that are inappropriate, like being very anxious around puppy dogs or something like that. The response could go up and down just independently of any particular cues, or the response could be appropriate, but then last for an excessive amount of time. Or the response could be appropriate but fade too quickly.

[Randolph Nesse]

Do you think I'm going to pause just for a second? Those categories you just listed are appropriate for almost every response. Those are the ways in which a control system can go wrong. And what you just said is more sophisticated than any psychiatry textbook, because what we should be doing for every patient who has control systems out of control, whether it's anxiety or depression or something else, we should be asking, in what way is this control system failing? Using what we know about control systems. And we're not doing that because we're not thinking about these as normal responses where the control system is wrong. We're just thinking about them as bad systems.

[Rob Wiblin]

Do you think it's the sheer complexity of getting all of those things right that might be a key driver of why all of us feel that sometimes we have psychological reactions to things that we're not finding help helpful. Even people who are not suffering severe mental health problems, we often feel like a lot of conflict for those. I wish I were different. I wish that my fear lasted less long. I wish that I had more of this response to this cue. But it's so hard to get right. Right.

[Randolph Nesse]

Well, Anne, all of those categories overlap with each other. So usually a bunch of them are all together and it's just too damn much anxiety. And it comes too easily and it lasts too long and it takes over mind too much. So it all tends to go together.

[Rob Wiblin]

In the book, you warn that in doing evolutionary medicine, there's maybe two big mistakes that people need to keep in mind in order to steer clear of them, and those are viewing symptoms as diseases and viewing diseases as adaptations. First off, what's an example of viewing symptoms as diseases?

[Randolph Nesse]

Viewing your ordinary fight flight response as if it's an abnormal response. It's not an abnormal response. It's a normal useful response in the right situation. And you were starting to go towards depression just a minute ago. It's much more difficult to figure out for low mood whether it's useful or not, because to do that you really have to understand the person's entire life situation. On the other side of it, though, you're about to ask me about tendencies to view diseases as if they're adaptations. There are a lot of pretty wacko ideas that have circulated in evolutionary psychiatry. I mean, how about this one? A lot of people who have schizophrenia, genetic disease, take special roles as shamans in their tribe, and therefore they get to stay home and have sex secretly with individuals when other people don't. And therefore they get a selective advantage. Well, I mean, most. I mean, that's just not right, you know, on about three or four counts. And actually I've really caricatured something. I mean, the person who proposed that is being quite thoughtful, actually, and trying to offer a real contribution. So I shouldn't make fun of it, but it's a good example of something just isn't. Or how about this one? Back to medicine. Some people have suggested that colorblindness might be useful because colorblind people can detect motion better. And having a few colorblind people in your group can help you detect motion in the trees, and therefore the group can shoot down the monkeys more easily. I'm sorry, that makes the mistake of saying that something that's good for bad for an individual might be selected for because it's good for the group. So I don't know about that.

[Rob Wiblin]

In the book, it sounded like you think that some personality disorders like narcissism or psychopathy or borderline might in fact be regarded as adaptations of a sort. That they might be be a sort of social strategy that just happens to work well for the individual's genes and maybe is very Unpleasant for the person themselves in some cases, although not others. But it's like we view it as a disease because it's bad for society, not because it's malfunctioning from a biological point of view. Is that right? Are there any other diseases that might be best understood as adaptations?

[Randolph Nesse]

So Linda Mealy, back in, I think, the 1970s or 80s, wrote a behavior and Brain Science article about psychopathy, you know, sociopaths, and suggested that this was a frequency dependent strategy. That if you were in an environment where there's a lot of suckers who are trusting individuals, you can get away with a lot and get a lot of resources and mates and have a lot of sex and have a lot of offspring. And this would explain the persistence of genes for that kind of sociopathic traits. But when those kind of genes and traits become more common, everybody becomes more suspicious and those things don't work so well anymore. It's a clever and interesting idea. And the evidence there's still. There's not agreement on this yet. I think it's very unlikely. I mean, part of the evidence that makes me skeptical is that sociopaths in small groups don't do very well. Richard Wrangham would point out how they get killed. And even in modern groups, you're liable to get put in prison or if you get caught lying too much. Although recent events have shown that you can lie a whole lot and get away with a whole lot if you have enough power and create a political force behind you. And the neurological aspects associated with sociopathy, in some cases, although the data on that is mixed, suggesting that. And then third possibility is that this whole ability and the careful things that make it, the things that make social life and relationships in groups possible, they're so damn subtle, a lot of people can't do them very well. And maybe another half a million years will make us all better at it. But in the meanwhile, it wouldn't be surprising if this is a capacity that's still evolving and some people get those mechanisms just don't work. Right. So I would not say that's an adaptation. But it's a very interesting idea about how there could be a genetic subset of individuals who pursue specialized strategies.

[Rob Wiblin]

Wouldn't it be a little bit hard to maintain these separate strategies because the genes get scrambled and mixed together. They're not like different subspecies that only breed among themselves. Right, Right.

[Randolph Nesse]

So that's another argument against this. This would be what's called a genetic morph. So in fish, for instance, you can have genetic morphs, some of which have different mating strategies. And they can be genetically different and they're maintained because as they get more rare, they get more successful. And so that's perfectly viable. But the key to those examples are that each different morph has to have the exact average fitness over the long run. And you have to have frequency dependent selection that makes the rare morph have more success when they get more rare. And in most cases, those mechanisms have to be changed just by one or two genes or a gene network because you've got to flip it to an entirely different strategy. Now that might be possible. And there are these different niches in social life. Dominant and submissive and cooperative and competitive. There are different niches in social groups that conceivably could do something like this. But I would say the evidence is out and I'm skeptical.

[Rob Wiblin]

Okay, so there's a lot of different mental health problem categories. The ones that personally I find most mysterious from an evolutionary point of view are depression and anxiety. Because of their very high prevalence, I think it's easy enough to imagine how a complex organ in the brain could break in 1% of people. Maybe seems to be the case in schizophrenia. But. But what's more baffling is that you could have 10% or more of people at any point in time who are taking a huge hit to their reproductive fitness because they're so worried that they can't leave the house, or so sad that they're struggling just to perform basic tasks. It feels like embarrassingly poor engineering. From an evolutionary point of view, that really begs for explanation. So we covered anxiety, which I feel is the easier of the two. But sadness and depression are a little bit slipperier and maybe resist a simple explanation. But let's start at the beginning. Why do you think humans and other animals have the capacity to feel sad at all? What's the point?

[Randolph Nesse]

So this takes us back to this distinction between sadness and depression. I'm so glad you're going this direction. Anxiety is protecting us against losses as possible and keeping us from going back in situations that cause losses. If you have a loss that causes sadness, and sadness doesn't seem like it's useful because, hey, the loss has already happened, what are you going to do about it? But in fact, there's a lot you can do about something if you've lost something. If your child has just been washed out into the surf, you can swim out after your child, you can tell other kids to get off the beach, you can prevent any of your children from ever going in the ocean again. You can get sympathy and help from other relatives. I mean, there are all these things you can do to prevent further losses immediately and further losses in the future. And if you lose your driver's license, you can get a different kind of wallet, so you're not as likely to lose it in the future. It's really good. Worse, I mean, if you say the wrong thing to your spouse and she won't talk to you for a week, you can learn to stop saying things like that. It's very good to feel sad and upset about making mistakes that cause losses. Where this really becomes awful, though, is losses of a loved one. And I spent three years of my life delving into a very detailed database where we looked at people who had experienced loss of a spouse. And they were asked 6 months, 18 months and 48 months later about all of the details. And we had a lot of information about them before they ever had the loss. And one of the questions was, gosh, is it true what we were all taught in psychiatry, that people who have ambivalent relationships need to get in touch with that ambivalence to get over their long term grief. And one of the profound findings from our research was that people who have ambivalent relationships before the loss don't have as much grief as other people. It's exactly the opposite of what we were all taught. Whoa. Plus, the theory in psychiatry was always that delayed, absent grief, people who don't grieve really have a problem and you need to get them in touch with their grief. More specifically based on Freudian theory, I spent many hours upon the direction of my well meaning supervisors trying to help people who are having bad long term grief get in touch with their anger towards the bereaved. Because Freud's idea was that suppressed anger was causing depression. And everybody has anger towards everybody at some time. So you can always find something like that. But in our data, we found no hint that people who didn't grieve immediately had more grief later. It was quite the opposite. What we really did discover that was profound in our study is that a lot of people who experienced a lot of grief at 6 months didn't remember anything about it at 48 months. They said no, grief never bothered me much. Conversely, a lot of people who didn't experience any grief initially later remembered themselves as having experienced it. It just refocused for me. It taught me once again that we humans are subjective beings. And the idea that we can remember things accurately about our emotional lives, not really. That's just not how we're designed. But now you're going to ask me, so why the hell is there grief which causes so much awfulness? This is an unsolved problem, Rob. Some people say it's an accident of our system for attachment. And other people say, and actually it's good to grieve the loss of a loved one, to help find them if, in fact, they're not dead, they're just lost in the savanna someplace, and to prevent other losses. This is a very profound question at the center of bereavement research.

[Rob Wiblin]

Yeah. So grief seems like a tricky one with zone issues. But I guess coming back to more mundane sadness, you mentioned there's a couple of different functions that it might serve. So one is kind of motivating us to try to undo the thing that's making us sad right now. Another is motivating us to kind of ruminate and learn from a negative experience in order to figure out how to not have it happen again in future. And another one is just learning or, like, motivating us to move away from whatever thing is making us sad right now. So kind of like a whip on.

[Randolph Nesse]

Our backs and stay away in the future. Which is a connection between anxiety and sadness.

[Rob Wiblin]

Yeah. How confident are we that those explanations for why sadness exists are correct? How do we figure out what the balance is between the different possible functions that we can imagine?

[Randolph Nesse]

That's a wonderful question. It's such an understudied problem. I mean, I wrote a chapter in this book on bereavement about the origins of sadness, but its utility is just vastly underappreciated.

[Rob Wiblin]

Yeah.

[Randolph Nesse]

And again, like anxiety, it's usually excessive. Usually we just feel more bad than we need to, and it doesn't do us any good.

[Rob Wiblin]

One thing that maybe we should have elaborated on earlier is the distinction between something being good for a person in terms of enjoying their life and something being good for someone's genes in terms of reproducing themselves. Do you want to highlight the difference between those two things?

[Randolph Nesse]

Yeah. I find this a shocking thing, Robin, and a disturbing idea. I mean, I always thought that natural selection would shape us for health and happiness and cooperation and long, happy lives. And anything different from that meant there's something wrong with the system. But once you start studying how evolution shapes behavior regulation mechanisms, you realize that it doesn't give a damn about us. It doesn't give a damn about anything. It's a mindless process that any genes that make individuals do things that benefit. Transmitting more genes, which basically means having more children and taking good care of them and getting resources to do that. Any genes that make make that happen will become more frequent. Any tendencies genetically to do things that make your life end sooner or have fewer offspring or have fewer resources, those are going to go away. And the whole system doesn't care at all. A lot of our bad feelings are about things that have to do with reproduction. And we should pause just a moment and note that Freud was right about one thing for sure. He said, ultimately it all comes down to sex. And, you know, it's not sex, it's reproduction. Sex is just one small part of having offspring and taking good care of them and raising them to a point where they can reproduce. But, you know, fundamentally, all of these systems are designed to maximize numbers of offspring and the benefits to relatives. And a lot of times that makes us miserable. I mean, bad things happen to our kids. Hey, that's not us, but we're wired appropriately. So to feel really, really bad if something bad is not if something's, you know, our kids are not doing well and we try to help them. So these are things that are built in. You don't want to change them because that would be awful to lose that kind of feeling for sex. It's more of a different matter. When people can't have sex, they really, really hate it. And that's pre wired. I think it'd be nice to just tell yourself, oh, I shouldn't care about that because that's about my genes and not me. But actually that doesn't help a bit knowing that a lot of things that we're doing, striving for status. However, a lot of your work with 80,000 hours, I think, has to do with people pursuing careers. And it's always a challenge to figure out how grand a goal to set and what to do when you're not making progress towards a relatively grand goal. And this is another area that I'd like to talk about at some point.

[Rob Wiblin]

Yeah, yeah, we'll come back to that one. Believe it or not, there's a whole other cluster of reasons for low mood that you describe in the book, which is around modulating effort and energy expenditure. That there's reasons why sometimes we want to feel excited and enthusiastic, and other times we want to feel down and unmotivated. Can you explain why it is that sometimes we should feel unmotivated?

[Randolph Nesse]

Right. So again, this whole line of thinking, first making sense out of anxiety and then recognizing that sadness and low mood are different, led me to ask this new question about low mood and depression. That is in what situation, is it best to be kind of pessimistic and low energy and not even eat much and all the rest? And there are a lot of different answers to that that are out there in the literature. Maybe it's like hibernation. Maybe low mood and depression are the right thing to do when you're in a cave in northern latitudes and it's the wintertime. Okay, well, maybe. Maybe it's good to not keep fighting and competing and striving if, in fact, somebody who is your superior has just beaten you in the status competition. And some of the most wonderful work early in evolutionary psychiatry was done by a psychiatrist named John Price, who studied chickens. And he looked at what happened after the chickens had a pecking order dispute. What happened to the one who lost? Well, it quit fighting at all and kind of went off by itself. And he said to himself, you know what? That's a good thing, because the chickens that keep fighting against another chicken that's stronger than they are just gets pecked more and more and more. And he came up with the wonderful idea called involuntary yielding. And he then studied monkeys. And the monkeys he studied had this amazing signal of their status. They had regular bright testicles, blue testicles, when they were in a dominant position. And when they lost the status competition, their testicles turned a dusky blue, and they huddled away in their cage and didn't fight with anybody and acted for all the world like they were depressed. And he pointed out that if they had kept fighting, if they kept fighting, they would have just got beat up more. And he then applied this to humans, and I think, quite profoundly pointed out that a lot of depressions result from involuntary yielding. That is, after we lose a competition, though, the system makes us giving up and thinking ill of ourselves and thinking hopeless thoughts that are unrealistic, often in order to keep us from getting beat up more.

[Rob Wiblin]

So those are some reasons why you might have low mood, normal low mood and sadness. How is it then that severe depression can be really common? This helps explain why there's a direction to move in. But why do so many people get stuck so far off in one direction where they can't even see, obviously, great opportunities that are in front of them, or they just keep trying to learn from the same bad experience for years at a time.

[Randolph Nesse]

Yeah, so this is, I think, the most important unanswered question in mood research. We need to try to understand severe depression in terms of how ordinary low mood is dysregulated. There is something called kindling at the foundation of A lot of depression research, kindling means, you know, when you start a fire. It comes from epilepsy research, really. If you induce seizures in an animal by putting electrical probes in the brain, it makes it more easy for them to have seizures in the future with lower stimulus of a drug or electrodes. And there's an analogy here with depression. People who have episodes of depression go into depression more likely the next time with fewer losses and lower stimuli. And that's usually been interpreted as something in the depression harming the brain. And in fact, there are some brain changes that are associated with depression. But another evolutionary interpretation is that there's a system that adjusts how easily depression goes off depending on what experiences you've had. And if you've had repeated experiences of failure, then going into the mode that's appropriate for failure more easily becomes easier. And now we're back into the same argument as we had for panic disorder. That is, it's a positive feedback process where the more depressed you are, the more you get depressed. And guess what? In modern life, this is such a huge problem for people because you can go to your room and you can shut the door and turn off your cell phone and then lie in your bed crying saying, how come nobody ever calls me because your cell phone's turned off? Or instead of calling somebody and going out and doing something, you could sit or eating junk food and watching television. And that's just like a recipe for becoming more and more and more depressed. And on top of that, you can not get any exercise, which is another recipe for being more depressed. This is not an adequate explanation, I want to emphasize, Rob. I mean, the real explanation for why low mood escalates into depression needs a lot more work. But there's a lot of work that's been done that nobody pays attention to. A fellow named Eric Klinger, a psychologist in Minnesota, has been writing back in the 1970s about the normal sequence of events when you're not making progress towards a goal. And it's quite profound work. He points out that the first thing you do is wait for a while, and the next thing you do is try a different strategy. And the next thing you do is give up completely for a while. Next thing you do is try another strategy, and the next thing you do is completely change your goal and recognize that you're never going to reach that goal. There's also other good research on this Jotter Heckhausen. And again, I'm going to really simplify subtle social science research. Carson Roche is another researcher who's Worked on this, showing that people who keep pursuing unreachable goals spiral into worse and worse depression. She was studying people, women who were approaching menopause, who wanted to have a child. That's a bad situation because you're doing more kinds of IVF and other kinds of things to try to have a child. It's not working. And this spending a lot of effort and time and worry trying to make something happen that it might not work. And then when many of these women reach menopause and give up on that, their depression goes away. And this whole line of research has made me change how I see patients. And it used to be that I would always encourage patients, keep trying, never give up. Your difficulty trying to do this is because of your depression. Don't let the depression get the better of you. And as I got older and I saw that not everybody can succeed in everything they're doing in life, I started just listening more and being more sympathetic and saying, gosh, can we talk more about why you feel you really have to apply to medical school for a fifth time or to somebody else? Can we talk more about why this is the only woman for you in the world and you feel like you shouldn't go on living unless this person will love you and can you? I mean, so often people are pursuing something that's very, very important, and you sympathize with them. And I think the key to good therapy in these situations is not just to tell them, don't pay attention to your depression. And it's not to just tell them, oh, you're never going to succeed at that. Give up. The thing is to talk with them about, gosh, do you think that's working? How much effort do you want to keep putting into this? Are there other things that would be better for you and your family than continuing to put in this effort towards getting that particular promotion or making that particular person respect you. On the other hand, it's not simple job because we all spend our lives pursuing unreachable goals. And the people who succeed grandly very often are the people who do pursue giant goals and fail over and over again and keep trying. So nothing simple here.

[Rob Wiblin]

Yeah. So think. That answer demonstrates how complex a question this is. And it suggests that depression, as a cluster of syndromes. Sorry, as a cluster of symptoms, is probably multiple different underlying maladies or there's multiple different independent ways that someone can end up stuck, extremely unhappy one that you elaborate on in the book, I guess, because maybe we have a better understanding of it and it might Also be really underrated is this issue of one reason that we need to get sad and one reason that it's maybe beneficial for our genes if we become like. If we have extended low mood is when we need to reassess a fundamental goal that we have in life, something that we've been working towards that's important to us, that we've been at for years, maybe that is part of our identity. It's not easy to get rid of those, to give up those goals, and it shouldn't be, because sometimes they're really important and you shouldn't be abandoning them. So you go through this kind of extended rumination, thinking, reevaluation process where at the end, if you ultimately decide that the thing that you're trying to pursue just ultimately isn't going to happen, it's not likely enough, then you can give up on that and replace it with something else and reconstruct your goals and your identity and so on. But it's possible to get stuck in that basically to be stuck in that status. If the thing that you describe is people who are. That they're stuck between the unacceptable and the impossible, where the goal that they're striving for is something that they can't give up. Like, I need to take care of my child, or I need to save my child's life because they have cancer, they can't abandon that goal. And yet they also maybe cannot succeed at it because there may just be no treatment that's available. And in that situation, we tend to just get stuck in this intermediate state of depression forever. Yeah. Is there anything you want to. For a long time. Is there anything you want to add to that?

[Randolph Nesse]

A lot to add to that. There's a wonderful book by a woman named Emmy Gutt, a Swedish psychoanalyst, called Productive and Unproductive Depression, where she goes through cases of public figures who basically are pursuing unreachable goals. And when depression is productive and when it's unproductive, I mean, for me, there's a bit of a paradox. I've gradually recognized that at the root of a lot of depression is hope. Wait, that seems crazy. I thought lack of hope was the essence, but. But there's a hope that you can eventually succeed at something that keeps people going, pursuing some goal that they're really not making any progress towards. Or as you say, that they just can't give up trying to get your kid off drugs. You can't and shouldn't give up on that. But on the other hand, dedicating your Life to it, when nothing you do is working, is a real good recipe for depression. I also talk about social traps. Social traps are when you're pursuing some kind of a goal but getting out of it. I remember one woman who was a very accomplished artist, and they had a house in an artistic area, except the fact that her husband spent about an hour on the phone downstairs every evening talking to his girlfriend, who he would occasionally go visit and have sex with. And she didn't want to stay with this guy, but leaving him would mean that she'd have to get a job and give up her art and her circle of friends and everything else. And. And we never found a good solution for that. I mean, I think a lot of people are in situations like that in their relationships. And Peter Kramer has written a book. You know Peter Kramer of listening to Prozac fame, wonderful, thoughtful psychiatrist, and he's written a book called should you'd leave? Because this dilemma is so central to so many lives. And again, it's not easy. None of these things are easy. But for me, I think I became a much better therapist once I started trying to understand really, what I call the motivational structure of each individual's life. That is, what's this person value? What are they trying to do? What do they have? What do they want? How are they trying to get it? How is it going? And most importantly, what's their expectation of the future? Because it's those future expectations that are more important for mood and all emotions than the current circumstances. Because our emotions are not based on events. They're based on our interpretation of what those events mean for our ability to make our goals. My colleague Phoebe Ellsworth and I wrote an article for American Psychologists about emotions and especially depression, pointing out that it's really how people assess. It's assessment theory and appraisal theory, but how we appraise the meaning of events for our personal goals to influence. One person loses a job, and so what? I never cared much about it. That's not the center of my life. I'll get another one and another person. It's been their whole goal, and they can't get another one. Fundamentally, you can't have a checklist that says lost job. How much importance is that for your mood? You really need to understand people one by one. You notice I'm saying that over and over again, Rob. And I think a lot of psychiatry these days has gone towards make a diagnosis, give the standardized drug treatment for that diagnosis. And it's important to make a diagnosis. It's important to give appropriate drugs and to be scientific about it that way. But I think we're missing the kind of information that other doctors take into account when they're treating pneumonia or seizures or anything else. We need to try to understand how this individual person came to this particular difficulty and at least try to use that information in helping them.

[Rob Wiblin]

Yeah, you have a great chapter on this challenge that psychiatry faces as a discipline where it needs to balance between making statistical generalizations and learning from large data sets of people and what things go well for them and what things go wrong and what treatments work. Balance that against the need to understand individual people and what has caused them to become depressed in this particular case, and both perspectives have value, I think. And in a very low resource environment, doing a very broad brush approach where you say, okay, this person has depression, we're going to give them antidepressants because we've only got an hour that we can spend with them, and this is the best that we can do. That might make sense. But in a high resource environment, you really want to be diving down into understanding what type of depression is this? What is driving it? Let's understand the narrative of this person. I thought it was a really good chapter of the book.

[Randolph Nesse]

In fact, I want to use a jargon that I gave rise to in that particular one. There are two kinds of explanation that we humans use for events. Some are ideographic narrative explanations where we talk about all of the sequences that led to this particular thing happening. The other are nomothetic generalizations about a general law. And this isn't just in psychology. This is in physics as well. If you want to explain the Moon, one kind of explanation is what's its bulk? And how does gravitation keep it in orbit around the Earth? A different kind of explanation gives the history of the Moon and tries to ask questions of was it captured from a circulating asteroid? Was it a piece of Earth that was knocked off by a passing meteor? Was it just an accumulation of dust? In the history of even celestial bodies can be interpreted in different ways. It's really an important part of science to try to understand events both in terms of the individual sequences for this particular example and the general ones. And I was really bothered by this because I would spend the morning at the Institute for Social Research doing statistics on databases with thousands of people trying to see what factors caused depression. Was it their sex, their age, their marital status, their income, how many traumatic events they had, and all the rest making generalizations about people with depression. Then in the afternoon I'd go down to the clinic and teach residents and see patients and we'd make a diagnosis. But then we'd talk for 15 or 20 minutes about, oh, yeah, this person got a divorce, but he really wants to get back with his wife and she won't speak with him. And he keeps trying and trying and trying to get her to speak with him. And he has another possibility. We make individualized assessments of people when we try to understand people. I think an evolutionary framework, Rob, gives us the hope of taking this ideographic data that's really the key to causation of emotions and putting it in a nomothetic framework. These are the only two jargony things in the book, I think, but I really like those two words and that they were first proposed by the provost at the University of Strasbourg in 1894 and gave rise to a whole field of social psychology.

[Rob Wiblin]

We just talked about one cluster of ways that someone can end up with depression when they're kind of getting a signal that they need to give up on a goal, but they're finding it extremely hard to give up on that goal. I think another cluster relates to, I think, sickness behaviour, where I think this is a term that possibly you or one of your colleagues came up with. So for all of my life until I heard this, I was like, obviously when you're sick, when you have a cold or when you have the flu, you have to conserve energy because I guess the disease is harming you and it's not possible to go out and do things very actively. But it turns out that it actually would be. It is physically possible for you to go out and do things very actively. And yet we feel driven to have. We feel driven to have low mood, we feel unmotivated when we're sick and we tend to just lie around in bed. That, according to evolutionary medicine, is an adaptive response, because when you're ill, you should be conserving energy. You're not likely to accomplish very much at other things in the meantime. Possibly you could make family members sick, could be in the mix as well.

[Randolph Nesse]

And not just because of conserving energy, but if you go out and try to run around and catching an impala, you're just gonna. Or if you try to fight with somebody, you're not gonna be in good shape to accomplish those things. You're in danger. If you overexert at a time when your body is not in good shape, it's better to wait. The person who first came up with the sickness behavior idea is Benjamin Hart and Doing work at University of California, Irvine. Marvelous work on animals and cows especially, and how behavior, the response to infection and all the rest. But this brings up a whole line of work on depression. There's been marvelous work on depression and inflammation and infection. And a lot of people, when they get infected, get depressed. And if people who take interferon, which is a drug that has been used for hepatitis C, it's our body's main defense against viruses, in a lot of people that just causes raging depression. And it's such a hard decision for patients who have a proneness to depression. They have hepatitis C and this drug is the only thing that can help. And if they take it, they're going to get possibly suicidally depressed. That is a problem. Fortunately, we don't have to deal with that anymore because there are better drugs for hepatitis C. Finally. But those studies really made the point that the body's response to viral infections especially sets off a whole syndrome of sickness behavior. And again, this is unknown. Is it just that the whole system is so crude that we start feeling bad about ourselves and suicidal? Is it just that the system is not very subtle and it can't get. Why can't the system just say stay at home and read a book and be happy doing that? But that's not how the system seems to work. I tend to think it's just a crude system that the same system that regulates competitions and social status also gets kicked off. Another way of looking at it is that the original mechanism that tones down our effort and makes us hopeless and less enthusiastic about things, it evolved from the appropriate response to sickness and infection and then it was co opted later to cope with these social kinds of situations. And I think that's testable by the way, if you start looking at allelic genetic variations at increased risk of depression and tracing to see how many of them are also related to abilities to defend against infection. Lots of good work being done about this currently, by the way. This leads to the hope that you can just take anti inflammatories to cure depression. Sadly, it doesn't work.

[Rob Wiblin]

Yeah, why doesn't it work? Do we have a theory for that?

[Randolph Nesse]

I still hope it can work and people continue to pursue this. But it appears that it's not just the downstream interleukin and cytokine things that mediate this, or if you block them, a lot of other things in the brain keep working. Now we're coming back to how these mechanisms are actually instantiated in the brain. It's not one particular circuit or One particular neurotransmitter. They're all interacting. And you can do one like you give a serotonin transmitter blocker, which increases the rate of serotonin. And I presume most of your listeners know that. It's way more complicated than that. Your serotonin levels go up within a few hours after taking a dose of Prozac or something like it. And your mood doesn't get better for a long time. It's probably because the way those agents work is by completely changing the sensitivity of all kinds of receptors in that system. And there are 22 different serotonin receptors that all get rebalanced once you flood the system with excess serotonin. So, again, good. And then I wish this research could work better and we could find better ways of getting a drug that just zaps depression quickly. But that's just like trying to find a drug that zaps pain without causing addiction. We haven't found any. We can sometimes block different aspects of the pain system. Like aspirin blocks one particular route, and Tylenol and acetaminophen blocks another particular route. Other agents block other routes. So we block different parts of those things. But this also is a clue to how antidepressants work. People assume that they're replenishing some normal missing substance of sorts. No, I think what they're doing is blocking the actions of a normal system. And I want to say one more thing before I go on one more step. It's sounding in this conversation like I think that most depression is caused by pursuing unreachable goals and that kind of thing. Maybe half, you know, and a good study about this has never been done. This would require going door to door, talking to people for hours and a random sample, and following people up over months to try to figure out what goals are pursuing, how it's going. And it'd be a very difficult project to do. But in my experience, and the second chapter of mine is called when the Moodostat Fails. And that indicates that some depression is at least aroused by kind of normal things, Even if it's overshooting other depression comes from the damn system is broken. And there are a lot of people who come into the clinic and say, I'm depressed, like my mother, like my brother who killed himself, like my grandfather who killed himself. That's a different question. That's the question of why is it that genesis that make some people more prone to depression than others persist in the population? A whole different question. And these people, I think there are a lot of people who really do have a brain disease. And we shouldn't argue about it's all social or it's all caused by events, or it's all genes. It's interactions for most people. And some people are at one extreme or the other.

[Rob Wiblin]

Yeah, I was going to say there's probably a whole lot of different causes. Is there another big cluster of causes of depression? I guess you were describing there that the mood is being broken, which I think is associated with a type of bipolar in particular, or I guess people who where their entire family suffers from depression.

[Randolph Nesse]

Some people have hereditary bipolar illness, but there can be hereditary unipolar illness of depression as well.

[Rob Wiblin]

Is there another cluster that we haven't talked about very much of, kind of an evolutionary explanation for how people can end up depressed?

[Randolph Nesse]

So a number of people. Ed Hagan has written a nice article in the Canadian Journal of Psychiatry about different origins of depression. And Marcus Rantella has written a chapter in the new Handbook of Evolutionary Psychiatry listing. He calls them different subtypes of depression. I would call them depression arising from different kinds of situations. And where I differ with some of my evolutionary colleagues in this area is that instead of assuming that there are different subtypes, it seems to me there's a global situation that ties all low mood and depression together. That is situations in which it's best to pull back not too so much, be pessimistic and inhibit your enthusiasm. And that can range from infection to losing a battle, to being in the winter in a cave in the northern Europe, or being in the savannah in a dry period when there's no game to be chased and killed, or being in a marriage that isn't working. And. And you don't know. And do all of these shape distinct kinds of depression, not distinct, but slightly separate. So I think there are a whole lot of different kinds of. What they all have together. It seems to me though, is being in a situation where pulling bad effort, saving effort, not being enthusiastic is often better. And in modern environments, it's hard to understand that because we're not trapped in a cave, we can go to the grocery store and get food and we can always see somebody. There's always some opportunity. And now you don't even have to go too far. We can get on Zoom or do a podcast with somebody and try to do something that we hope will be productive.

[Rob Wiblin]

In the book, you do some modeling of the hypothetical reproductive success of organisms that experience big mood swings versus other similar organisms that barely have any mood swings at all. You look at the environmental circumstances under which one approach beats the other, in which mood is useful versus mood is not, is not helpful. In what circumstances in that model, is it indeed worth having big mood swings?

[Randolph Nesse]

So, again, let's make a dimension here between individuals who never experience any variation in mood and individuals who have wild swings in mood. Not so much bipolar, but individuals who have a more borderline personality where their emotions swing wildly depending on events. For bipolar individuals, it often gets set off by events, but it becomes autonomous from events much, much more often. I mean, first, let's just note, humans vary a lot. I mean, there are a lot of people who. You talk to them about mood and they say, yeah, I never get very up or down. And then you talk to other people. You know, somebody looks at them wrong and they go to bed for the next three days. Or somebody says, you know, you're really attractive, and they think about that constantly and get wildly excited. Or they dump their whole bank account into a new venture to start a new business, even though there's no real business plan to make it work. Someplace in between, on average, is best. And what you're just suggesting is that that whole system might want to be adjusted depending on the situation. And I think that's optimal, isn't it, to adjust your levels of effort so that you put in more effort in situations. I use the word propitiousness. Propitious just means a situation where small efforts pay off big. And unpropitious means the situation where no matter what you do, it's not going to work. So I think there are some patients, some people who just never experience much mood, other people who experience really wild mood swings. And it's fascinating that natural selection has not narrow that down to a much more narrow distribution. And now I'm going to try to answer your question after that. Sorry for this sideways thing, but there are situations where it's really good to ramp up your effort dramatically. Falling in love, for instance, thinking about that constantly and having the opportunity to have a wonderful partner and not seeing anything wrong with that person, no matter what. I mean, that's a marvelous thing. And it's one of the most wonderful experiences in life. Some people never experience it. About a third of people in some samples never really experience falling in love. And there are other people who fall in love once and the person doesn't want anything to do with them. They spend the rest of their life just stuck on that person. I mean, both of those extremes are not so good. Paradoxically, each of the people who tend towards both of Those extremes have advantages as well as disadvantages. An individual who really gets enthusiastic about things when there's an opportunity has an advantage over a person who's more towards the middle. In some respects. The person who doesn't get too much bothered by things doesn't get into depression the way other people do.

[Rob Wiblin]

So if I recall in the model, you kind of model basically an organism over time where it can experience high mood, in which case it's inclined to put a lot of effort into trying to go and collect food and so on, or it can experience low mood, in which case it kind of stays away and doesn't invest any resources in trying to collect food. And some organisms, they'll fly between high and low mood quite quickly, depending on circumstances. And other ones will just put in the same amount of effort into collecting food every day. And basically, which of these strategies, which of these kind of psychological strategies does best in the long run depends on what kind of the cycle is on food availability basically over time. So if it's the case that food being available yesterday is very predictive of food also being highly available today, then you want to have mood swings because you want to say, like yesterday things went well, now I want to remain motivated and I want to go all out today and put in a lot of energy in order to try to collect a whole lot of food. If, on the other hand, how things were yesterday doesn't really predict how propitious the situation is today, then there's no point having mood, then having big mood swings will just cause you to over invest in effort today, even though you're not likely to get an especially high return. And it was quite fragile in your modeling. It seemed like quite small differences in the parameters could cause a moody or non moody strategy to win out. And that might help to explain how it is that there is such large variation between people, because it's actually not clear which of these strategies is best overall, given that the circumstances are constantly changing.

[Randolph Nesse]

So I think once this is published, I'm going to go back and listen to what you just said again, because you just made me very happy. You've increased my mood. Thank you, Rob.

[Rob Wiblin]

All right.

[Randolph Nesse]

I think very few people have understood that argument, although I've tried to make it in a few talks that came from a simple Excel spreadsheet model that I developed and worked on for several years. And Eric Jackson, who is a graduate student with me at University of Michigan, took that and made a much more fancy mathematical model of it. And the upside is just what you say you put in these parameters and you have a tiny bit of noise into the system about what the payoff is. The plus is plus or minus 10% in each move of the game. And you try to see which strategy works best. Stable mood or slight variations or big variations. And guess what? All you do is push the button and run the whole thing again, and it comes out different. Which one wins. Then you've just summarized a really good reason why natural selection would shape a bunch of widely varying mood regulation mechanisms. And some individuals in that little mathematical model crash into depression and just stay there. And others win the game. And you push the button and run it again. And the strategy that won the game last time crashes and dies. So the little tiny variation. This is a whole feature of complexity theory. Complexity theory teaches us that minor variations you can hardly tell lead to big variations in outcome. The butterfly effect is an example in climate. The idea that a butterfly flaps its wings in a slightly different way in Honduras might change air currents that change a thunderstorm in Oklahoma a week later. Kind of preposterous. But the idea is there, and I think it's real, that little tiny things can change those systems in terms of how they evolve. And little tiny events in our lives can change how we respond to situations in ways that send our moon up or down or sideways.

[Rob Wiblin]

I think many people will have the idea that the reason we get depressed is that we live in a very different environment in the modern world, that one that we're really not evolutionarily adapted to. And it's the mismatch between the situations that we're evolved for and the situations, the bizarre situation that we actually find ourselves in that explains intense sadness being triggered inappropriately. To what extent do you think that mismatch can explain severe depression in the modern world?

[Randolph Nesse]

I wish I knew. And I think that's one of the most important areas of research we could possibly be doing now. Depression rates in the United States are eight or 10 times higher than those in Japan and Korea. If we could get our depression rates here down to those in those countries. You do more for public health and mental health than all of the research and treatment we're doing. And yet nobody's looking very hard at what's different. And there are a lot of things that are different. I mean, social structures in particular are different with family structures. I went to Japan and did a study one time asking people, how are you different from other people? Because that was my favorite personality question for people in the United States. And, boy, did that teach me a lesson. Rob, to a person, they said, oh, I'm not different from other people. I am the same as other people. You ask that same question in the usa. The person says, well, I am kind of aggressive and I'm a sports person, or I'm very artistic. But if you go to a different culture that's more inclusive, with an Eastern kind of mentality, there's a much tighter social structure. I think my colleague Shinomura Kitayama and my friend and colleague Richard Nisbett are kind of the pioneers in cross cultural psychology. And these point out these profound social structural differences in different cultures, which may be responsible for differences in depression. But then people eat differently and exercise differently and have different access to drugs in different neighborhoods and different social services. In Japan and Korea also, it would really be important to discover what those differences are. And now I'm going back and try to answer your question. You were asking more about whether modern life in general does this. And I think that's another even harder to answer question. I kept asking one friend, Kim Hill, year after year, an anthropologist, very famous anthropologist every year I kept asking him, Kim, how much depression is there in your group that he studies? He studies a tribe in South America and he says, no, not really depression. They have people who have wisdom teeth oozing and people who have tuberculosis and people who are. But I don't see much depression. Then he started a medical clinic and what problems came in. I'm nauseated all the time. I wake up too early, I don't have any appetite and I'm pessimistic. Well, guess what? So it's very hard in a small group though, to do proper epidemiology. I mean, if you're only going to have 1 to 10% of individuals having a problem, it's very hard to do statistics with a group of 30 or 50 or 100 people are trying to do that. With the Aceh, there's a good group trying to work on this. But the answer, Rob, is we do not know rates of these disorders and other gatherer groups. We don't even have very good data about ancestral groups where we do have historical records. And the data looking at like the last 30 or 40 years, which is what a lot of people are concerned about, remains uncertain. Again, in a Canadian study, people have gone back and asked the same people the same questions and they don't see much increase. But again, there may be increases. And I'm particularly interested in the role of diet and exercise and people's ability to close themselves in a room and Escalate ordinary low mood into depression. And I'm also particularly interested in the tendency for everybody to strive for greatness that seems to be advocated in the United States in particular. And many Western cultures and universities are constantly saying, live a balanced life, live a mentally healthy life. And then the next minute they send you something every month saying, how many major awards or grants have you gotten this month?

[Rob Wiblin]

Mixed messages.

[Randolph Nesse]

Yes.

[Rob Wiblin]

I very frequently hear the claim that in countries like the US and the uk, mental health is getting worse and more people have depression and anxiety than have ever had it before. I guess the data behind that has always seemed a little bit hazy to me because it's something that's quite hard to figure out. Do you have a take on whether that is true or not?

[Randolph Nesse]

Yeah, a lot of my work has been with epidemiologists, and I always ask them about that. It's a great example of how information transmission is distorted because everybody wants to hear something new and dramatic and horrible. The evidence is very poor for that. People went back in one study in Canada to visit the same people 30 years later and asked the exact same people the exact same questions. No real evidence of increased anxiety or depression. Furthermore, Ron Kessler, who's probably the world's leading epidemiologist for psychiatry, did a study during COVID I mean, everybody was about the COVID epidemic of mental health disorders. And he did an actual proper study, randomly selected people asking all the right questions. And his conclusion was, gosh, there's not really much evidence for increased rates of severe disorders. Maybe a little bit of mild things. Now, that's not to say this doesn't deserve further study. There's also a study in the UK of young people who use social media a lot. And it looks like maybe they do have increased rates of problems, which is entire. I mean, so we need to keep an eye on this kind of thing. It also looks like during the cocaine epidemic in the 80s and early 90s, there may have been increases because so many people were wrecking their lives with cocaine and methamphetamine. But the whole idea, I mean, people used to think, oh, well, back in the good old days, these things weren't problems. There's so much more attention to them because of television advertisements for antidepressants and outreach programs to identify people with depression, many of them sponsored by drug companies. They can be helpful, but they also get people thinking and more comfortable revealing their symptoms in a way that makes the news media seem to find lots more depression and anxiety when it's very hard to actually do the studies and show that that's actually increasing that much. Which isn't to say it isn't a gigantic problem. I mean, the overall rates of anxiety, anxiety and depression just by themselves cause medical morbidity, that is inability to go to work and early death and things like that. Equal to almost all other disorders, not just mental disorders, but other disorders. These are gigantic world problems. And again, this takes us back to the core problem. I mean, who the hell designed this thing? How come we're all so vulnerable to so much useless suffering?

[Rob Wiblin]

Yeah, it's an interesting social phenomenon that the news and people in general in conversation are extremely excited to talk about anything that's getting worse. If the trend is bad, then people are very excited about it and want to focus on it. And I think mental health is probably more like. More probably something that's like roughly flat but just extremely bad. The total burden of disease is enormous, and it doesn't have to be getting worse in order for it to be a massive problem that deserves a lot of attention.

[Randolph Nesse]

But this takes us to a few of the mind itself, just briefly. I mean, it's so terrible that our minds automatically focus on problems. When you're lying in bed at night thinking about some problem, somebody you're not getting along with, or some bad decision you need to make, and you tell yourself, I can't solve that tonight. Quit thinking about it, and your mind immediately goes back to it. It's just like your tongue going back to the canker sore in your mouth. You know, I've been there. It's just the way the mind is designed. And it makes sense that it should use those calculation powers to solve problems. But boy, is it a problem for us.

[Rob Wiblin]

Yeah, so we'll come back to bad for us, but maybe good for our genes. So, pushing on a bit from depression, I want to put a very simple evolutionary model to you for why we might expect not just our brains, but our bodies to be constantly breaking down. And I'm kind of curious to know, given that, to what degree do we really need particular explanations for particular diseases? So humans reproduce sexually, and a key reason for that, we believe, is that it's in order to keep up with pathogens that have a much faster generation cycle than humans. Because if we didn't have a more clever way of recombining our genes, then they would just out evolve us and crush us, the bacteria and viruses. So that means every generation of genes are recombined in all sorts of crazy ways that haven't been tested before. That could potentially lead to incompatibilities. And every generation you get a normal distribution around the mean of the traits of both parents. So two parents who are both 6ft tall could potentially have a kid who's 6, 5, just by random chance because of the genes that that kid happened to inherit from them and the various interactions between them. Now, if this is true for most important traits, then maybe we should be pretty unsurprised to find that two parents who have a normal mood level could by chance give birth to someone who is really morose or who is really enthusiastic all the time, that they could have just inherited a lot of genes promoting sadness because of bad luck, or maybe they got an unlucky combination of genes, genes that shared on the same gene and clash with one another and somehow produce a bad outcome. So our biology, another factor apart from the combinatorial thing, is just that our biology can only do so much to stop random mutations creeping into the genome with every generation as our DNA gets copied. So there's kind of constant mutations, constant variations being generated, which creates further potential. It's easy to break things than it is to improve them. So that creates a lot of potential ways for important mechanisms in the body to break down. So the resulting increasing dispersion of traits, the kind of spreading out, I'm putting my hands in the middle and pulling them apart here. That dispersion of traits with each generation is then offset by a stabilizing selection where kind of the unfortunate people who end up too far on the extremes in either direction on any super important characteristic get weeded out by natural selection because they disproportionately fail to reproduce themselves because they're either supermanic and they end up falling off the edge of a cliff, or they're incredibly morose and they don't get anything done. So some people end up way too anxious or depressed as a new evolutionary experiment, and they kind of drop out of the gene pool. How much ill health and mental health problems can we explain with that evolutionary, very general evolutionary model?

[Randolph Nesse]

So I think you're spot on in pointing out the way natural selection maintains variation is crucial for understanding this. But there's several levels of variation. You've emphasized sex and it does recombine genes, but of course it doesn't create any new genes or add or subtract any genes from the gene pool. Mutation is another way that new variation comes in. Developmental variation I think is underappreciated as a possible source of variation. And in a project I'm working on right now, With a biochemist and geneticist at Duke, Fred Nightout, we're looking at what's called epistasis, and that really is the interaction of genes. So just as you say, the child of those two individuals who are both stable in their mood is going to get a mixture of genes. But the reason that child is different is because those genes interact differently with each other. And we're thinking that this may well help to explain why so many disorders, including even things like schizophrenia and autism, are highly heritable. That means that whether you get them or not depends on what genes you have. But we can't find any specific genes of big effects. It's. It's thousands and thousands of genes of miniscule effects. And our idea is that it's this epistatic interactions of genes that might account for both the heritability and phenotypic or disease differences between individuals. But that's turning out to be a very tricky project, both mathematically in terms of our modeling and in terms of trying to catch up with a very difficult literature. Evolutionary biologists have been thinking about 100 years now about why variation persists. R.A. fisher was very deep into this, and Haldane was deep into this. Could it possibly be because mutations are good for the species? That doesn't work. That one doesn't work. But could it be because maintaining some level of very. I'm not going to go more into the deep theory here, but you put your finger on a very profound question or problem and possible answer. And now let's go to connect this, what we talked about before. Natural selection is going to create a range of individuals that maximize gene transmission on average, no matter what happens to the individuals. I mean, it doesn't really care if some individual gets sicker or not. It ends up shaping systems that maximize gene transmission. And my other research on this is what's called cliff edge effect. And the idea there is that natural selection shapes some traits to a level where the person has maximum benefits. Right at the edge of a cliff edge, at a peaky, peaky peak. That's really great. Maximizes fitness. Unless you go one step further and fall off the edge and the whole system collapses. This is like a race car. You can make your race car lighter and lighter, and the lighter you make it, the more races you win, the faster it goes. But of course, if you make it lighter and lighter, it's also more likely to collapse and break. And it's entirely plausible to me that very, very strong selection for capacities for cognition and social thinking and emotional management in the last hundred thousand years because we're in a new environment now, not just our hamburgers and our comfort, but we've been in a new social environment for the past few hundred thousand years where your reproductive success depends mostly, mostly on your social relationships. And man, is it hard for us. This is what we think about lying in our beds at night is our social relationships and did we blow it? And what should we do and all. And it may be that the process is still ongoing and it's gradually making us better and better at those kinds of things. It's partly because those situations are intrinsically difficult, because different people have different desires and they can conflict with each other. And it could be because of what I call a wrenching transition. Because when natural selection shapes some trait to maximize its performance, if it's rapid selection for something like ability to think about logically and have consciousness, it might well wreck a lot of other things. The little mutation that makes one thing work better is almost certainly going to screw up a few other things because of the system being complex the way it is. And there's some evidence for this. Even this kind of stuff is so thrilling, Rob, because it starts off as speculation. And now that we have so much genomic data, it looks like we can test some of these things. If you look at the genetic variations that increase the risk of schizophrenia, most of them are ancestral, they're very old. But if you look at genetic variations that decrease the risk of schizophrenia, most of those are new in the last few hundred thousand years, suggesting that this strong selection for cognitive abilities and social abilities recently, recently being a few hundred thousand years might well have screwed up a lot of things that natural selection is gradually fixing with other mutations.

[Rob Wiblin]

Yeah, let's just pause and talk about that cliff edge fitness function thing again because that is a, that's a really interesting idea that you present in the book. That is quite challenging. I think it takes a minute to fully appreciate. I think the example of this that made it clearest to me was imagining humans are evolving over time to become more intelligent and to have bigger brains and bigger heads. And you can imagine that there might be very big fitness returns, very big reproduction returns to being born with a larger head and a more developed brain. But as the head of an infant gets bigger and bigger, every so often, this is going to cause the death of both the baby and the mother because the baby is no longer able to like they have to come out at some point. In fact, humans come out of the womb are extremely undeveloped relative to other animals. They can almost barely survive when they're out, relative to many other species. But at the point it comes out, if it's too big, then both the mother and the baby can die. Now how will our genes deal with this situation where there's big returns to having a bigger head and a bigger brain, but at some point it risks being a bit too big and everything is destroyed. It's going to find the kind of optimal level and then go a little bit short of that because it's so catastrophic when both the baby and the mother die. But it's going to accept a pretty high maternal mortality rate because there's just such large returns to having a very big head. And our genes and evolution do not give a flying damn about our well being. If 10% of mothers and babies dying maximizes the expected reproduction because the other 90% are doing really well, that's just collateral damage that our genes and evolution will accept. So this is something you elaborate on in the book a whole bunch. And you apply it to the case of schizophrenia, where it might be that having a modest amount of the genes that cause schizophrenia is good for us, but then if you tip over too far, then you could end up with an extreme case where reproductive fitness is massively damaged. But I got the impression from the book that this was a kind of cutting edge idea, that maybe this wasn't so broadly accepted and this was one that you were hoping to develop.

[Randolph Nesse]

How's it not accepted at all? And I. I'm delighted to see that other people are picking it up. In particular, your idea about obstetric dilemma has been picked up by Mitteracker and Mihaila Peblicev, who published an article in the Proceedings of National Sciences a few years ago explicitly using the cliff edge idea for what they call the obstetric dilemma and showing that it would do exactly what you said. I think there are multiple explanations for difficulty in childbirth. However, it's not just the size of the head. Apparently in modern environments, people eat a lot more sugar and they're larger and they're more diabetes, which makes babies bigger in general. And also standing upright changes the anatomy of the pelvis in ways that may make it more difficult to have passage through the birth canal. And we should pause here for a minute to say just how limited natural selection is. I mean, isn't it stupid that that baby has to pass through a narrow ring of bone? I mean, why not just have it come out through the belly button? It's just ridiculous. But that can't be fixed. That's a great example of what we call path dependence. You can't reroute the baby's exit from.

[Rob Wiblin]

The womb, it's fixed because there's no intermediate states that function. Basically.

[Randolph Nesse]

That's right. And cesarean section works pretty well these days. So another factor.

[Rob Wiblin]

Before we move on from the book, I want to grab, to point to one remaining gem in the book. You offer a very partial defence of Freudian psychoanalysis, which you say is totally stigmatized these days. And it's almost slightly gut wrenching and fear inducing to go out and say something positive about it, at least among the people that you know. But you say, nonetheless, it does have one core important idea in it that we shouldn't throw out with the bathwater. Which idea is that?

[Randolph Nesse]

Before we get to the idea, can I just say that my book has wonderfully received hardly any criticism. Everybody says, this is interesting. This sounds right. Except for that chapter about psychoanalysis. Several of my friends said, why did you put that in? Don't you know that that's just a bunch of hokum? And I said, well, I understand you're a biologist, but no, it's not all hokum. We really do have an unconscious. There really are defenses. Some. Some symptoms really do come from the way those defenses work. Relationships often are wrecked by unconscious processes that we're only partly aware of. And psychotherapy that gradually brings some of these unconscious ideas and emotions to consciousness can be very, very helpful. I mean, I found knowledge about the unconscious and trying to understand my potential unconscious motives extremely helpful in my own life. I've never been psychoanalyzed, but the core idea, I think is very valuable. But I can also kind of see why people just dump on it, because there's a lot of ridiculous stuff.

[Rob Wiblin]

Freud himself in particular, is not a paragon of epistemic or other virtue. And I guess psychoanalysis is a discipline. It seems like the treatments that it's developed in many cases were not very helpful. So I think that's turned people off.

[Randolph Nesse]

They can be very. I mean, I've conducted long term psychoanalytic treatments, not psychoanalysis, for a number of patients. And some of them had quite miraculous results. I think it's in general true of psychotherapy that the benefit comes much more from the nature of the relationship with the therapist than from the nature of the theory that the patient and the therapist use to understand the person's situation. But I'm impressed by the power of psychoanalytic understanding and free association to understand things about a person's life that Otherwise aren't there. On the other hand, and the one thing I'm now going to finally answer your question that I find especially valuable is trying to understand how natural selection, we very often believe we don't have motives that we really have. And this is so useful to help us to really and truly give up on goals we can't reach. I never wanted to have children. I never wanted to get rich. Yeah, she dumped on me, but she was really a not good person anyhow. And it's just as well that we didn't get together that kind of sour grape stinking. All those are very useful ways of coping with these kinds of problems We've just been talking about, about pursuing unreachable goals. Much better to really and truly give up on those. And if you don't do that. I had one friend who spent a lot of time trying to pick what car to buy and bought a BMW and immediately had regrets and said, oh, I don't know if it's the right car, there's something wrong with this person. And what's wrong is that most of us, after we make a decision, immediately get convinced that we made the best decision. This is dissonance theory in social psychology terms. We immediately are pretty sure we may. And you can do lots of experiments on this. You give people a choice between a pen and a cup and they choose the cup and ask them later, did you make the right choice? How much would you pay to take it back? And they'd pay more to take the cup back. Just great social psychological research. But this is a good example of distortions in our cognition that are useful because once you make a decision, it's really best to just stick by it instead of continually ruminating about whether you made the right decision. And there are people whose mental disorder consists of being unable to have confidence in their decisions. It has to do with obsessiveness and obsessive compulsive disorder. It's not exactly obsessive compulsive disorder. My point here is that distortions that make us believe we made the right decision and that distort reality can be very useful, especially in adjusting our goals so that we put our effort towards things that are useful instead of wasting effort and making ourselves miserable about other things.

[Rob Wiblin]

Yeah, I think the idea that has come up on the show before is that there are self serving motives that from an evolutionary point of view it would be good if we could act on. But from a social point of view it would be best if that were not very salient. If it were not very salient to us, what was driving our behavior. Because the more conscious that it is, the more likely we are to leak the fact that that is our true motive to other people. And that plays into, I think, the unconscious Freudian idea to some extent.

[Randolph Nesse]

Okay, you just extended our interview by 20 minutes at least. We need to talk about the origins of morality and genuine love and the problem of simplistic selfish gene thinking. So the reason I wrote those articles about psychoanalysis was because of talking with one of the wonderful biologists at University of Michigan, Dick Alexander, and one of the wonderful biologists of our time, Robert Trivers, and they had both written articles suggesting that the reason we have an unconscious is so that we can pursue our own selfish motives without knowing it and better deceive other people and accomplish our goals. So you can tell somebody you love them passionately with a full heart and then just have sex with them and leave the next day. I mean, that was kind of the simplistic version of the argument. And I thought, well, that sounds awfully cynical. Not only that, it doesn't match what I'm seeing in my practice. I'm seeing people who lie awake nights wondering if they accidentally didn't smile at somebody, you know, or if they accidentally took a person's parking spot, that they didn't. You know, people are very sensitive. How is it possible that we have these feelings of moral obligation and shame and guilt, even towards people we're not related to? I mean, the great discovery by Bill Hamilton and George Williams of, you know, if you do things for your kin who share your genes, you can sacrifice a lot for them because they have the same genes. That's called kin selection. But I've become fascinated by the origins of morality and very distressed by the possibility that selfish gene thinking can make people cynical. And I've seen it make people cynical. They say, well, natural selection can only preserve genes that make us have more offspring, and therefore everything we do is basically selfish. Well, everything we do is basically in the interests of our genes in the long run, on the average. But that doesn't mean that we're all being selfish. And in fact, selfish people don't do very well at all. The people who do best, we can tell from an evolutionary viewpoint, on average, are those who have a moral sense and those who are loyal to their friends. We know this because most people are like that, and people who aren't like that, that don't do very well except in large, great places where they can get away with stuff and move on to a different town, another time. So this led me to literally decades of trying to understand this. I first did what's called commitment theory and did a whole book on evolution and commitment. But then gradually, I followed the work of Mary Jane West Eberhard, an insect biologist who talks about what she calls social selection. And her point is so simple and so profound. She says that just as individuals pick out the best potential sexual partner, creating extreme traits like a peacock's tail, and that's why the peacock's tail really drags the peacocks down, right? But it's beneficial to the peacock's genes, even though not to the peacock. And she says, just as that happens for sexual selection, we also pick our social partners. And we're trying to find some social partner who has things to offer, like resources and integrity and caring about us and the like. And I took that idea and ran with it and wrote several articles about partner choice as the way that natural selection shapes our capacities for morality and genuine relationships that are not just exchanging favors, because that real good relationships are not just exchanging favors. Or you care about somebody and you don't want a relationship with somebody who says, oh, you invited me over to dinner, so I'm going to invite you. No, that's not how it works. The way it works for most people is, gosh, I really like you. Let's have some time together. Isn't it wonderful that we're not like chimpanzees? We really have capacities for genuine morality and love and friendship. It's astounding. And nothing about selfish gene theory makes that untrue. We need an explanation. I think the explanation is that we are constantly trying to be the kind of person other people want to be a partner with, and there's big competition for that. And there's a lot of good psychological work about competitive altruism where people compete to be more altruistic than others. And I think there's a good reason for that. So this explains. I'm going to wrap this up by going back to social anxiety and guilt. Because why do people have so much social anxiety? Because being very sensitive is generally a good thing for your genes, if not necessarily for you. And why do people have so much guilt and worry so much that they might have accidentally offended somebody? Because having that moral sense really is very important. People who don't have that moral sense don't have very many friends, or at least their friends are just friends who want to get something and trade favors instead of friends who will actually care for them when they really need help. End of little lecture. But I think a big reason why evolutionary psychology hasn't caught on more is because a lot of people have a simplistic version of selfish gene theory and they think it implies cynicism and it implies everybody's just out to have as much sex as they can. But taking a step back and looking at how natural selection shapes our capacities for morality and loving relationships, I think is the antidote that can make all of this grow in a healthy way.

[Rob Wiblin]

Yes. I think that the kind of cynicism in the thing that I was just saying, I think it does explain some things. I think it is true that we do hide some self serving motivations.

[Randolph Nesse]

I should say. I also conclude Travers and Alexander are right. We do hide our motives from ourselves to get advantages also. Yes.

[Rob Wiblin]

But it's a bit of a. It's a slightly dangerous idea I think because I've seen some people latch onto this and it just becomes a hammer. Then they just like want to hit every nail basically with this explanation. Anytime someone does something, they just claim that it's self serving and it's very hard to disprove because of these kind of cynical explanations.

[Randolph Nesse]

You ran into a building to rescue your child. That wasn't altruistic. You were just doing it for your genes. Right?

[Rob Wiblin]

Yeah. One thing I see on Twitter because of my association with effective altruism, people saying this is such a common line. There is no true altruism because people only do things for self serving reasons in order to promote their genes. No one says there's no true anger because people only express anger or appearance to act angry in order to promote their genes. It's clear that people do have sincere anger or they certainly experience an actor.

[Randolph Nesse]

That's wonderful. So I think in the long run this might be my most important contribution and I need to get back to writing. But I'll emphasize it. Peter Hammerstein has written about this with Ronald Noyes. He. Noyes is an economist and they've written a lot about partner choice which is essentially the same thing. They don't quite emphasize as much as I do the, the capacity of this to create human morality and guilt and the emotional aspects of it. But I think this isn't just my idea, but it hasn't been appreciated nearly as much as I think it could be appreciated as a place for generating extreme traits that are bad for the individual but good for that individual's genes and for that individual's relationships.

[Rob Wiblin]

Yeah. I've been hoping to get Richard Wrangham on the show at some point to talk about the domestication hypothesis. There's actually quite a dark side to this whole thing of how we behave.

[Randolph Nesse]

He has very different view of these origins. And he points out that people who don't do the right things are liable to get killed.

[Rob Wiblin]

Right. I was going to say that's the dark side is that you don't think that that's. This is a real rabbit hole.

[Randolph Nesse]

Well, it happens. And I think that is the dark side, which is the opposite selection force. But I think he minimizes the importance of. Of who you get to be partners with. And it's really. Let's go one step further on this. This creates unfairness because those people who have the most resources and can afford to offer the most to other people and they can afford to be honest and they can afford to be loyal. And not only that, because they have resources and are loyal and are honest and are empathic, they get the best partners. So all these people who have the most to offer pair up with each other, and people at the middle pair up with each other. And this ends up with a lot of people not having many opportunities for good relationships where they're going to get mutual benefits. And this is kind of like the structure of society. And it's not so easy for people who either are not blessed with a lot of empathy or don't have a lot of other resources or not very attractive. And I think those of us who have advantages shouldn't just say how great we're doing. This whole process of shaping things by partner choice can be pretty brutal for other people.

[Rob Wiblin]

Okay. I want to move on from good reasons for bad feelings in particular, and think about how evolutionary reasoning might be able to improve medicine more generally, not just in mental health. So you started out really frustrated by psychiatry that you helped get evolutionary medicine going. Then you came back to work on evolutionary psychiatry. It's been kind of a long career of trying to get these different perspectives off the ground and actually into some sort of practice. Yeah. What has been accomplished by evolutionary or Darwinian medicine so far? I guess maybe other than the improvements to cancer treatment, which I think is a pretty clear case that we've actually talked about in a previous episode 144 with Athena Actippus. Maybe we could quickly talk about that. But are there interesting other cases?

[Randolph Nesse]

Yeah, there sure are. It turns out that the ideas that George Williams and I just promoted about trying to ask why natural selection didn't do a better job remains profound. And we can come to other examples of that in a way. But practical factors have much more to do with things that evolve fast, that are small, like cancer cells and bacteria and viruses. And I think the second area where there's been the greatest advance is in using evolutionary theory to understand the evolution of bacteria and viruses and how competition with them shapes defenses that are very dangerous. I mean, the two biggest problems we have these days, other than the mental disorders we're talking about and cancer, are infectious diseases. And our defenses against infectious diseases, autoimmune diseases, the whole immune system is poised on this cliff edge. It's not even a cliff edge. It's a pinnacle where too much and you start attacking your own cells. Too little and you get killed by a virus or bacteria. So is there a perfect place in between where you never get autoimmune disease and you completely get protection against bacteria and viruses? No. At whatever point you are on that continuum, you're going to have some risk of autoimmune disease and some risk of getting bad infections. So this is called a trade off. And this is one of the core principles George Williams and I propose for revolutionary medicine is, is every trait in the body is not perfect. It's a trade off between advantages and disadvantages. And people have been looking at this and finding new ways to use antibiotics more effectively. They've found ways, for instance, of essentially making it more expensive for the antibiotic resistant bacteria to replicate than the ones that are not antibiotic resistant. And so getting rid of the antibiotic resistant ones and letting the other ones grow and then smearing them again with a new antibiotic, also in cancer treatment. And this is a poignant thing. When I was a medical student, I treated many. You know, it was my job to give the infusions to kids with Hodgkin's disease. And in those days, they had some chance of surviving if they got the right chemotherapy. Repeatedly, we made them very sick. It was awful business to do, and a lot of them died. It was wrong. What we were doing was we were assuming that we gave one drug at a time because the doctors in charge said we've got to save other drugs in case this one doesn't work. Now, triple drug therapy is the routine, because what you do if you give one drug first is create a selection of cells in the body that are resistant to that drug, and then you give the second one and make them resistant to a second drug and a third drug. I mean, much better to use three drugs all at once if you want to get rid of everything. So it's just I strayed from antibiotics to cancer. But it's all basically the same principle. And I mean, Andrew Reed is doing this really creative work trying to use mathematical modeling to better understand when we should take antibiotics. Here's something where there's been a huge change in basic medicine which hasn't been attributed to evolutionary medicine, but probably should be. Doctors for years have told their patients, you've got to take all the antibiotics in the bottle to prevent resistance and do it for the good of the community, if not just for yourself. People would take all the pills in the bottle. And Andrew Reed for many years had pointed out, actually, that makes no sense. What you need to do is take enough antibiotics so your immune system can clean up the rest of the. Any additional antibiotics you take is just creating antibiotic resistant organisms that are going to spread in the community. And there were a number of other very sophisticated, mathematical, evolutionarily sophisticated models. Finally, about six years ago and Major Lancet published an article called the Antibiotic Course has run its course. You no longer need to tell people to keep taking pills after their fever is gone. It's not necessary. We've done studies to prove it. That article, Rob, it made no mention of evolutionary biology, no mention of natural selection, and no mention of the 10 people who'd spent their life working to show that that wasn't really necessary. So there's this complete disconnect between antibiotic use and evolutionary biology. But it's now coming together. And now more and more people studying infectious disease are recognizing that we need mathematically sophisticated, evolutionary sophisticated strategies for dealing with the gigantic problem of antibiotic resistance.

[Rob Wiblin]

It sounds like you think that practical, like clinicians who are treating patients maybe are not so friendly in some way, or they don't understand or they don't appreciate, or maybe they have a distaste for evolutionary medicine or evolutionary biology.

[Randolph Nesse]

I've hardly ever found. I mean, occasionally you find someone who just thinks evolution is a bad idea because of religious stuff and the like. But no, almost everybody, if you explain it in a sensible way, say, oh, wow, that's very interesting. Now, it doesn't and shouldn't in general change how you practice medicine quickly. I tell people, if you find a doctor who says, I'm an evolutionary doctor, I practice a special kind of medicine, I tell them, run, you should always practice medicine based on the best double blind controls, you know, and not pursue theory, but they're cool things. One project George Williams and I worked on is asking why there is bilirubin in the body. Bilirubin, you know, is the yellow stuff that makes your eyes go yellow when your liver isn't working right. But it's very weird because it's toxic, it's hard to excrete, and the body spends energy to make it from biliverdin, which is a hemoglobin breakdown production. Why does the body do that? It turns out it's a pretty good antioxidant. For a long lived species, this can be quite useful. And in fact, there's a psychiatry researcher on the east coast who did knockout studies genetically showing if you knock out the system that generates the bilirubin cells die much more quickly because of oxidative damage. And more recently, people have shown that people who have a syndrome that makes their bilirubin levels about twice normal just throughout life. They're kind of nauseated and slightly yellow, and they don't do as well as other people overall in life, but their rate of heart attacks is cut in half. Very interesting. Now, people are suggesting that you might in fact want to increase people's bilirubin levels in certain circumstances as a therapy. So there are all kinds of things like this that are just ready and waiting for evolutionary thinking to guide us in possibly understanding the origins of the disease better. How about nearsightedness? I mean, 80% of young people in Korea are now nearsighted. And in China, they've mandated that every child has to spend at least an hour outside in the sunshine every day to prevent nearsightedness. But do we really know what causes nearsightedness? No, it's astounding. We don't know that. Is it lack of sunshine? Is it being indoors in closed spaces? Is it eating too much sugar?

[Rob Wiblin]

Well, we know it's something about the modern environment, right? Because rates have gone from very low to extremely high. So something about.

[Randolph Nesse]

So I made a nuisance of myself in my ophthalmology class and in front of 200 students as a medical student, the guy was talking whether or not you get nearsightedness, 80%, 90% of that has to do with your genesis. And the professor was saying, it's a genetic disease. Natural selection is just screwed up in some people. And so I raised my hand and said, that's not possible. Natural selection would eliminate that because guys like me would be tiger food. And they said, Dr. Ness, you just have to get used to the fact that natural selection just makes mistakes. So that's one thing that stuck with me. It's not just that natural selection makes mistakes. It turns out that there's a mechanism in the eye for it to grow very, very fast when the image is unclear. And that allows children to keep a constant accurate image on their retina, even as their eye grows. And if that system overshoots because it's getting a constant blur image, the eye grows too far. And that's nearsightedness. So there's a system in there that's very sophisticated, but it's not working right in modern environments. And we still don't know what's doing it. And we really should.

[Rob Wiblin]

Autoimmune disorders are a huge cluster that do an enormous amount of damage. And as you were saying, they arise because we need to have a very powerful vigilant immune system in order to fight off pathogens. But then if it's slightly too overactive or responds to the wrong things, then it can just start destroying our own tissues. And that can be incredibly destructive. Does evolutionary medicine give us any ideas about how we might treat that better?

[Randolph Nesse]

So before we go into treatment, let's go into causes. This is an area where there really is good evidence of things getting much worse. In the last 50 years, during the course of my career, I've seen the rates of irritable, of bowel disease, inflammatory bowel disease, and diabetes and multiple sclerosis. They're skyrocketing. And asthma too. Why is that? It's just something is different in our environment and we don't know what it is. We do know that kids who get multiple antibiotic doses in their first year of life are several times more likely to get asthma and other kinds of allergic diseases later. Will antibiotics also explain increased rate of autoimmune diseases? I haven't looked into that literature. People are working on this. I haven't looked into it in recent years. But there's something that's doing that dramatically. Could it be something in our food, some additive? Could it be just that we live in a clean environment? Graham Rook in the UK is the architect of what's called a hygiene hypothesis. And he's pointed out that we're just not as exposed to as many pathogens that we used to before. We don't get as many infections and we get a lot of vaccinations that protect us. And this makes the immune system not generate the same kinds of, of factors that decrease immune responses. Furthermore, in ancestral times, everybody had worms in their gut and worms in their body. And that stimulates certain substances in the immune system that down regulate the whole system. And people in ancestral environments basically don't get very many immune diseases at all. But Most of the research that the National Institutes of Allergy and Infectious Disease are sponsoring on these things is looking at just at the mechanisms. What's the mechanism that goes wrong in somebody who has multiple sclerosis? What's the mechanism that goes wrong in somebody who has some kind of skin abnormality? That's autoimmune. Those are important research projects, and they're leading to new treatments. But we really should be taking the evolutionary view and trying to ask ourselves, why is it that natural selections left us vulnerable, and what is it about the modern environment that makes it a problem for all of us? Now, all of these are heritable disorders. A big mistake a lot of people make is to say, oh, what do you get? Multiple sclerosis depends a lot on your genes, therefore it's a genetic disorder. But those genes didn't cause any harm back when George Williams and I called those genetic quirks instead of abnormalities because they were neutral back then. They only cause problems in modern environments.

[Rob Wiblin]

What do you think are the biggest opportunities for evolutionary medicine to make a difference in the next few decades?

[Randolph Nesse]

Gosh, there's a marvelous series of commentaries on this that you can find on YouTube. I gave a little kickoff talk, and then five other experts weighed in on what's the future of evolutionary medicine? And I think I'll refer people that instead of trying to recall, call it all right now, I'll just mention referring back. And I think we're coming to the end of our time together. One of the greatest opportunities is in psychiatry. And it's been very gratifying for me to realize that a lot of people are sharing this view, that we really can use an evolutionary perspective to make sense out of mental disorders, instead of this simplistic view that each are separate disorders caused by specific genes or specific brain loci, and instead try to start understanding mental disorders the same way we understand other medical disorders in terms of how the systems work, how they were shaped, why naftular system left them vulnerable, and how we can use that knowledge to better help our patients. Again, this is not a new method of therapy, but it's a fundamentally new way of. I even dare call it the P word. It's a new paradigm for understanding why we're vulnerable to these disorders. Disorders. And it's working. And I think that's a huge opportunity. Very satisfying.

[Rob Wiblin]

Pushing onto a new theme, there's a sophisticated objection that I've heard to evolutionary psychology from someone who really is super informed about it. This is that evolutionary psychology, and I guess by extension kind of all of the reasoning that we've been doing today about, at least about mental life, it'll often reason that it would have been evolutionary beneficial if people had had a strong proclivity to do or believe acts. For example, if someone tells you that something and they're a competitor in a status competition, then wouldn't it be good if we were skeptical of that claim? Because in the ancestral environment, it might have been bad for your reproductive fitness to believe them because they might be scheming against you, some story like that. The reasoning runs that because it would have been beneficial to have a given instinct programmed into us, we will necessarily evolve to have that instinct. But obviously there's a lot of sense to that. It's a good starting point. But there are many ways that kind of psychological tendencies, which would have been good for us and might be good for us now, even just from our genes point of view, might just fail to arise. So one key reason would be that there might just be no practical way for it to evolve. So we only have, astonishingly, about 20,000 genes in the human genome coding for about 100,000 proteins. The entire human genome, including all junk DNA, is only about about 700 megabytes long. And if you focus just on the clearly functional gene parts of it, the protein coding parts, it would be 25 megabytes of data. And of course, most of those genes are dealing with internal organs other than the brain or the nervous system. They're just making the gut work or the heart function. And so there's just not a lot of material, there's not a lot of data going into the production of actually producing a brain. And obviously the brain has to be kind of like networked from nothing, but basically just based on some pretty sort of science.

[Randolph Nesse]

So you've gone on from a generalized critique of evolutionary psychology to the possibility that the genes don't have enough power to do what needs to be done. So let me take part one first, and I'm going to take it up to the next level. Rob, I think there is a general tendency that we do have that's dramatically illustrated by the controversies about evolutionary psychology. And that tendency is for people to take simplistic views that are all positive or all negative about any group and then stick with those and either attack it constantly or support it constantly. It's one of the deepest tendencies in human nature, it seems to me, and it's exemplified by these debates about evolutionary psychology. I encourage people not to participate in them because it doesn't get you anyplace. You Might as well talk about the Irish or, you know, or about matter, about any group.

[Rob Wiblin]

You know, this person actually isn't against evolutionary psychology. This critique, I think, is not about matter.

[Randolph Nesse]

Any generalizations about a field. I mean, don't do that. Astrology, okay? If you want to criticize astrology, it's not grounded in science, okay? But we know natural selection acts. We know evolution is responsible for why organisms are the way they are. What we should be doing for each of these things is taking the very specific hypothesis and seeing what we can say exactly what it is, and then getting people together to say what evidence would weigh for or against it. These generalized things about evolutionary psychology, I think, are just a waste of time. Let's do it one at a time. Even then, it's really hard. I think you mentioned at one point something about the preference for mates in mid cycle. Women in mid cycle.

[Rob Wiblin]

Well, that's a very famous hypothesis. Yeah.

[Randolph Nesse]

I convened a group in London when I was in Sabbatical in 2010. Specifically, I wanted this group to come up with standards of evidence for evolutionary psychology. And the first thing we were going to do is all agree on whether or not that hypothesis was true. After four meetings, half the people said, well, it's obviously true, it has to be. And the other four people said, it's ridiculous. Obviously it's ridiculous. That's a really gross simplification for some very smart people making good arguments. But it was a real lesson for me that people take sides and then they defend whatever side they're on. As for evolutionary psychiatry, you can't be for or against evolutionary psychiatry. It's just using a basic science, however we possibly can, to better understand why we're vulnerable to mental disorders. It's not a method of treatment that works or doesn't work. It's just adding in a basic science. And by the way, we're just getting started on it and it's going to take a lot of time and a lot of people's effort to actually figure out how to make the best use. We're going to make a lot of mistakes along the way because that always happens and it's a process.

[Rob Wiblin]

So I think the bottom line that comes out of this thinking about mechanistically how would different mental capacities, different proclivities evolve isn't that evolution hasn't shaped our minds or evolution hasn't shaped our character or what things were or how we react, react to things. Obviously it has. Obviously we want food and we find it delicious because that helped us to survive. I Think the thing that comes out of it is that the more specific a hypothesis is, the more it's saying that in this very narrow circumstance, or in this very particular case, that only describes 2% of experience in the ancestral environment. If there's a particular behavior that would have been good in that maybe evolution just doesn't have the selection power or it doesn't have enough genes or just doesn't have enough selection power to program for something that would not be beneficial, like. Like a sufficient fraction of the time.

[Randolph Nesse]

So I don't think the argument that there are not enough genes works because we know that 90% of the alleles that influence mental disorders are not protein coding. They're sitting in what we used to call junk DNA. And I've done a number of projects recently just looking at how we can use all the information in the genome to better understand why some people are vulnerable and why people aren't. So I don't think that argument works. And how and our minds work. I mean, we can do calculus, for God's sake. Natural selection never shaped that. It's just astounding. The things that we can do, and these are basically epiphenomena, they're not shaped by natural selection, but they're pretty neat things that we can do, even aside from direct actions of natural selection. But the argument that there's variation that leaves some people vulnerable, however, is a very good one. And that's because I think on the average, fitness functions are fairly flat and a lot of wide variation is not going to influence fitness all that much. You could talk about that as weakness of natural selection, but it really is that selection forces are going different directions for different people in different environments. And therefore we maintain a lot of variation, both genetically and phenotypically. And then there are all these genetic interactions with each other that I mentioned before. So there's a lot of things going on here. Again, we're going way beyond what's known. But it's so exciting that we're now getting this genomic data that makes it possible to actually assess some of these ideas.

[Rob Wiblin]

Yeah. What have you learned over the years about how to best weed out evolutionary explanations for why we are the way we are that are actually correct versus ones that are plausible and have some reasonable theoretical basis, but as it turns out, just red herrings.

[Randolph Nesse]

So I refer people to my article about 10 Questions to Ask about evolutionary explanations for disease. Where I lay it out, it's not as simple as I would like it to be, and I'm not even going to try to summarize it here, except to say even framing exactly what the hypothesis is is usually very difficult. And there's a huge distinction that needs to be made between hypotheses about why we all have traits. Why do we all like sexual partners of a certain appearance? Or why do we find foul, why do we find feces disgusting? There are things we all have in common that are simple like that. But most of the more interesting ideas are about what we call facultative adaptations. Basically responses that go off in a certain circumstance. And if you're in a cold environment, you shiver. If you're in a hot environment, you sweat. Those are facultative adaptations. Natural selection is shaped mechanisms that detect the situation and set off an appropriate response. And much of our behavior is also a product of those kinds of facultative adaptations. But the situations are not as specific as being cold or being hot. They're situations like somebody looks at you and you're trying to tell if they want to have sex with you or they want you to pass them the butter. And so this idea that there are simple, discrete mechanisms for each situation, I don't think that's right. But a lot of people disagree with me about that. And I think this is going to be a continuing issue that people will work on over coming years.

[Rob Wiblin]

Okay, let's talk about this topic that you've been kind of itching to raise, which is about striving and careers and the unhappiness that can result in not so. This is in part a show about how working hard to figure out how we can make the world a better place is maybe something that people ought to be doing. And I don't actually think that listeners to this show have worse mental health than the background rate, but I think they are more likely to have a very particular kind of archetypal mental health problem, which is sort of a sadness that results from striving, where people who are doing very well and impressive stuff by any objective measure nonetheless feel like they're falling short of their own very high standards. Standards. This is something that we've talked about on the show before. In episode 149, Tim Le Bon on how altruistic perfectionism is self defeating and episode 100, having a successful career with depression, anxiety and imposter syndrome. Do you have any particular evolutionary psychiatry take on what a career or a big altruistic ambition represents for people?

[Randolph Nesse]

So in my really first big article about evolutionary psychiatry, and especially about mood, is actually the. The first article published in The New Millennium. In the best journal in psychiatry, I speculated about so what the heck could explain this general tendency for depression? And it seemed to me possible that a tendency to strive for grand goals even beyond what was accomplishable, might give certain individuals a big advantage, even though it made most people miserable. Because most of us fail. In fact, we all fail constantly. But. But continuing to strive towards large social goals, it seemed to me to might be a tendency that natural selection had shaped. Even though it leads most of us to be miserable and feel inadequate most of the time. That's pure speculation, Rob. I don't know anything about how you would test that kind of thing, but it does seem to be true to me that at least in the cultures I'm familiar with, which may be very different elsewhere in the academic cultures, most everybody is striving for greatness, you know, and in sports world, you know, everybody wants to be messy and you know, it's just all the movies get made about the people, you know, who win. Nobody makes the movies about the other 10,000 people who've dedicated their lives to becoming soccer stars and never quite make it even to a second rate league. On the other hand, a lot of people have fun playing soccer and enjoy their lives and do the best we can. And that I think is. I love the motto carved in stone on a prep school that was near where I grew up. It was aim high but not too high. And I thought, I've always appreciated that.

[Rob Wiblin]

Yeah. Is there a bit of an evolutionary psychology mystery of why it is that human beings, or at least some of us, are inclined to strive for enormous goals that we're probably unlikely to accomplish or to care about such extremely big picture things that we have such a tiny influence over. You could imagine alternative species like Humans prime, where they tend to just focus on their family, or they tend to just focus on quite narrow things that they can control and they're satisfied when they accomplish the basic task of finding food and reproducing. But at least in the modern environment, at least with the current culture that we have in the countries that I'm familiar with, many people seem to stray often a very strange direction. That is a little bit hard to comprehend from an evolutionary point of view.

[Randolph Nesse]

Well, and social media I think could well augment this in a way that's quite toxic for a lot of people. By leading, anybody can become a TikTok star and earn $200,000 a year starting next year and something. And so I think it encourages a lot of people to put a lot of effort into things that on the average never pay off. But for a few people they do. And those are the only people that we see. We don't see everybody else struggling and striving. But I haven't answered your question about. I mean, I think before taking another step though, this is an area where making generalizations about human nature just from modern Western cultures is a mistake. I'm guessing that this super striving and the like is amplified dramatically in Western cultures. Yeah, but I don't know. This would be a good question for Shinobu Kitayama and Richard Nisbett. Maybe you'd like to have them on sometime and talk about cross cultural psychology. It's very relevant to their kinds of work.

[Rob Wiblin]

I feel like I'm really torn on this question of whether having a big ambitious goal is bad for people's mental health or not. Because there's one narrative on which having a very ambitious goal makes you more vulnerable to anxiety and depression. Because you're going to be very worried that you're going to fail at it, because you probably will fail at it. And it makes you more likely to be depressed because when you fail at it, you're going to feel unhappy with that and feel like you've fallen short. On the other hand, there's this other narrative that having a big goal in life, a goal bigger than yourself, is really motivating and people find that exciting and that it's exhilarating. It gives you a reason to get up in the morning. I mean, I guess both of these could be true for different people, depending on their psychology.

[Randolph Nesse]

There's a good research on this, actually. Two psychologists in Florida named Carver and Shire have done a whole lifetime of research showing that mood is not a product of what you get or don't get. Mood is a product of your rate of progress towards your current goals. What a profound insight. And clinically, this means that they've done studies of people pursuing mazes and all kinds of things. And it's true. I mean, I think the happiest lives are people who have goals that they can make steady progress towards and it doesn't matter whether you ever get there. But if you want to be a poet and you're writing poetry and some people appreciate it, and you get some poems published, maybe even you can feel like you're doing something profound and useful and interesting that other people appreciate and you don't have to become the world's best poet and win prizes. You might keep trying for that, but I think you can have a very satisfying Life pursuing that kind of goal. But again, there's other goals where people say, I need to be a billionaire by age 30. Go for it if you want to, but it's not going to bring you happiness, I don't think. And you're probably going to fail. But this comes back to clinical work. Again, Rob, Trying to understand what a person is trying to do and how it's going and where it's likely to go, I think is the absolute center of trying to understand people. It's the motivational structure of people's lives. And trying to treat people with anxiety and depression without doing that, I think is just like trying to do internal medicine without weighing people and taking their temperature. We really need to do an assessment of people's motivational structures in order to figure out where they're at.

[Rob Wiblin]

It seems like some people can remain cheerful or really motivated trying to accomplish some big global goal, even if it's not apparent that they're going to succeed. It's not apparent that they're actually going to become an mp. It's not apparent that the policy change that they're after is going to happen. And I wonder what is happening in their minds in this structure where what matters is making progress towards a goal, not necessarily accomplishing it. I wonder if some people are inclined to think, well, each day I go into work, I try to get this massive policy change at the national level level. And they feel like when they're doing work, when they're kind of getting intermediate outputs, when people are. They're persuaded one person of their point of view. For some people, that is a reward where they say, yes, I'm making progress towards accomplishing my goal. Maybe other people are stuck in the mindset where they're saying, have we achieved the policy outcome yet? Is the legislation passed? And whenever the answer comes back no, then they feel like I'm not making progress towards my goal. And so they feel like very beaten down when after a long period of time, maybe years, working at something, they haven't accomplished the ultimate big outcome that they were seeking. Yeah. Does that seem like. Because I wonder, how can people aim for big goals without becoming miserable?

[Randolph Nesse]

You know, there's a wide variation in this, isn't there? And there are some people who are really quite happy just puddling along and doing what they're doing and not. Not all that ambitious. And they can live very happy lives. And I envy many of them. And there are other people who succeed grandly. As a professor of psychiatry, I saw a number of VIPs who were Vice presidents on their way to becoming president of their firms, or really wealthy lawyers and other kinds of things. And they were miserable because they felt like they were failures because whatever they accomplished, and there's a feedback process here where often the people who accomplish the most are those who are most driven to accomplish things and they sacrifice other things in life. And here's where it gets more interesting. People don't just have one goal and it's not just a career goal. They have multiple goals. And life gets complicated because all of those goals interfere with each other. I had two cases at Michigan of young men, not so young anymore in their 30s, who whole goal in life was to become a famous poet. And you don't get a job becoming a famous poet. So what you do is you drive a taxi and you write poetry in your off hours and when you're waiting for rides. The problem came up for both of these young men is that they wanted to get married. And their potential spouses were very reluctant to marry somebody who wouldn't have enough money for a house or raising kids. And that's a dilemma. This is one of those social traps where you have a big goal and in order to pursue another goal, you have to give up one. And this is again, this is why we lie awake at night. This is why life is not simple. And glib advice of any kind won't cut it. I think we need to try to understand people one by one and try to help them figure out what they want and what's going to work for them.

[Rob Wiblin]

I don't know whether I'm doing my job as a good employee of 80,000 hours in saying this, but I'm going to say it anyway. Over the years I have really come to be more skeptical of the idea that having very big goals in life, very big ambitions in life is good for one's personal well being. I think there are a bunch of advantages, but it seems like it does for many people. It comes at a, at a really large cost to the, to their mentor, to their mental health. Because. Well, actually I think, I think the more common thing is just like feeling a bit down, feeling, having low mood because the thing that you're imagining and like the thing you're trying to accomplish or you're thinking about all this so frequently is something that is 99% out of your hands, it's 99% out of your control. And I guess it is such a big part of Anglo culture and I guess within Anglo culture, American culture specifically, that people are strongly encouraged to have very big, ambitious goals, at least people who go to university, I suppose, or people who go to elite universities. It's absolutely drilled into us that we should be accomplishing great things for the world and that that is the natural order of things and how everyone ought to be thinking about life, that it's almost hard to, like, step outside that and imagine that you could have any other way of living.

[Randolph Nesse]

But if you're making progress towards a goal, and especially if you're with. I mean, what you've created, it seems to me, is a group of people who are all doing this together and who are helping other people to pursue their goals, and that creates a community. And I think when we're in a community trying to pursue a shared goal, that's the best possible circumstance if we feel like we're making progress towards that goal. But the other part of what you're doing with your group, if I understand it right, is you're not just encouraging people to find a job in finance to get rich. You're encouraging people to find a position in life where they can pursue a goal that's going to make the world a better place. And I think those kind of motives often bring people together and give people a sense of meaning and process and importance for their life. And even if you can never accomplish it, I mean, we're never going to make the world the kind of place we want to make it, right? So should we give up? No, I think what you're trying to do is noble and wonderful, and people trying to help other people to find special social roles where they can feel their work is meaningful. I mean, I remember back in high school, our teacher asked, what's the goal of life? And almost everybody else said, happiness and money. And I said, I don't think so. It doesn't seem quite right to me, and I don't think it is quite. I mean, people have to strive for those things. But more importantly, people strive for meaning. And meaning comes from having some goal that's larger than ourselves and trying to pursue it. And I think that's what your group is trying to help people to accomplish and to extent that's possible. It's wonderful. But the flip side of that is it's kind of a luxury, isn't it? Because there's so many.

[Rob Wiblin]

It's absolutely a luxury. It's 100% a luxury.

[Randolph Nesse]

There's so many people I see in clinic and they need a job to support their family and keep their car going. And this idea of devoting their working hours to something that's meaningful and fulfilling. I mean, that's not in the cards. And it's best if they don't try to give up. They need a job on the other hand. And one can also have different attitudes towards any job. I've just come back from a trip in Italy and dining in Italy is such a pleasure because the food is better than any place else, except maybe France. But more than that, the social structure makes it very clear that the people who wait tables are very proud of their skills and they take great pride in doing it well and providing a cup. It's just so wonderful to see people at all levels of society and the like having special skills that they're proud of and often feeling good. I think every night that they've done their job well and been appreciated by other people. That's what we all want, is to be appreciated by other people. And unfortunately there are a lot of jobs these days where people are not appreciated by other people. And that's a whole other problem that causes a lot of problems.

[Rob Wiblin]

Yes, I think the, the problem that I'm worrying about is absolutely something that people can only enjoy. It's a problem that people can only enjoy when they're extremely privileged and they don't have to worry about their own material scarcity so much. And they're focused a lot on me.

[Randolph Nesse]

Not extremely privileged, just okay. I think there are a lot of people who can do things good for the world at all levels of society. And I think there are a lot of people at high levels of society who are trapped, just telling stories about finances to trick people into investing.

[Rob Wiblin]

So there'd be this complete opposite cluster, I imagine, of people who become unhappy or anxious because they feel like they have no goal in life because they are not deeply attached to anything that they're trying to accomplish. And they don't feel like they have a moral framework or a spiritual framework or some framework that gives purpose and structure to their lives. And that's something that I almost never see, I would say, because so many of the people I know are just extremely driven to accomplish something and they know why they're doing it in order to raise the well being of other other people or to make the world a better place. But I imagine that while that carries issues, it shields you from this alternative cluster of meaninglessness.

[Randolph Nesse]

Yeah, so I find that. I see that as well. And I emphasized before, I don't think even half of the people I see with depression are struggling with pursuing an unreachable goal. I think a lot of them are just depressed. And I think the system of brain chemistry turns off motivation for some people. It makes them think everything is possible, makes them think that they are worthless, and makes them think that nothing is worthwhile at all. So that's a whole nother ball of wax.

[Rob Wiblin]

I've managed to make having kind of large goals where I'm trying to improve the world in a big way consistent with also being quite cheerful and having quite resilient mental health. I think that the way that I've made that work in the long term is there is this big goal out there that you're ultimately trying to accomplish, but you don't think about that all that often. That might guide the kind of job that you take or the problem that you're working on. But then day to day you have to kind of forget about that and instead focus on the things that you were describing, which is like the people that you're working with. The sense of camaraderie, the sense of accomplishment, that you've managed to get something done that day. You need to then shrink your ambitions on a day to day basis to something where you do have much more control over what is possible. And also, I mean, I think there's something to be said for aiming high, but then also predicting how much you go. Like saying, realistically, I'm only going to get halfway towards what would be imaginably possible.

[Randolph Nesse]

So can I tell you about my life and career for a moment, Ralph, please, go for it. I've been going for 40 years now trying to bring evolutionary biology to medicine as a basic science that's been missing for medicine. And I mean, just this week I've been extremely enthused because I'm writing the foreword for a book about how evolutionary medicine is transforming cancer understanding and treatment in positive ways. It's made me feel like, hey, maybe this book that I wrote 30 years ago inspired people to do, do things that are actually improving human health, that kind of thing. On the other hand, is my goal going to be achieved? No medical school teaches evolutionary biology really at all. And it's looking very likely that my goal of bringing evolutionary biology to medical schools will never be achieved, or at least certainly not in my lifetime. What about bringing evolutionary biology as a foundation for psychiatry? There's been a great new interest. There's really a wonderful group in the UK called the Evolutionary Psychiatry Special Interest Group, run by Riyadh Abev and Paul Senjan Smith. They've got a wonderful group of thousand psychiatrists, some who share their interests and Are trying to develop evolutionary psychiatry. Published a really good Cambridge university press volume. But how much progress are we making in actually encouraging psychiatrists to learn these basic principles and apply them in their work? Not much at all. Everybody's much more interested in psilocybin and other kinds of drugs and treatments and the like. And when I pull back and I'm realistic and I think, okay, Nesse, do you really have something that's offered that's going to make everybody's treatment better tomorrow? And I don't. What I have to offer is a new framework for thinking about these disorders in a way that I think helps everybody get a more appropriate perspective and do better research and understand their own lives better. But there's no instant cure for something. You can't do a double blind study about evolutionary psychiatry versus it's a whole framework for understanding things that I think provides a more solid, what we call a biopsychosocial model. So why am I not miserable? Sometimes I do get miserable and just kind of angry and hopeless about the slow progress. But what happened to Darwin's ideas, by the way? 1859, he published Origin of Species. Forty years later, at the turn of the millennium, previous millennium, what did people think of Darwin's ideas? Most scientists have said, oh, it was interesting, but it was wrong.

[Rob Wiblin]

Whoa, really?

[Randolph Nesse]

Yeah. They thought his idea of inheritance was wrong. It was wrong. And it wasn't until really the 30s and 40s that people started mixing evolutionary evolution with genetics. That recognition grew that this natural selection stuff was real. It was only in the 80s and 90s that recognition really grew in behavioral ecology that evolutionary explanations for behaviors and emotions were appropriate. Patience is necessary. And if in the process of pursuing these large and grand goals, we can find some comrades who share our interests and who can help us celebrate small bits of progress and people who share our enthusiasm, I think that makes life wonderful.

[Rob Wiblin]

Okay, we're getting close to the end of the conversation, I guess. One final topic I wanted to ask you about. Is aging a topic that gets closer to my heart with every year? I think it's so normal just to think. Well, obviously organisms have to age and die Just because machines break down. Humans just have to break down the same way. There's nothing that we could do. But I think evolutionary biology brings a slightly different perspective from an evolutionary point of view. Why is it that we age in the way that we do?

[Randolph Nesse]

Well, machines break down because there's no way they can replace parts. But organisms can replace parts. A lizard can grow a new tail, and some organisms look like it can live almost forever by replacing parts. There are big differences. And again, this takes us full circle from where I began in evolutionary medicine to where we should, where I am now as an aging person and where we should probably wrap up this conversation. As an undergraduate, I had an aspiring teacher named Patrick Milburn. I don't know if he's still with us, but he encouraged us to take on a really big project that we were very interested in. And I said, well, how about if we try to decide why agenting exists? Because genes influence your rate of aging. I think natural selection should have eliminated them. And bless his heart, he said, go for it, Randy. That's a very interesting question. I mean, most people would have said, you're too young. You don't know anything. But he said, go for it. So I took the bus. This was back before Internet or anything. I took the bus to the University of Minnesota and took my index cards and tried to look up articles about it. I never found the most profound article. I'll get to that in a minute. And I came up with a good idea. My good idea was that it would be good for the species if natural selection made some individuals die each year so that the population could turn over and the species could evolve faster and adapt to changing environments. And my professor said, that's brilliant. A another professor in the same department said, I think there's something wrong with that, but I don't know what it is. And I thought, well, that's interesting to come up with an idea that one person liked, the other person ate. And then it wasn't until I got together with that group of biologists at the University of Michigan when I was in 1980s and I was trying to pour out an evolutionary foundation for my work in psychiatry, I finally got my nerve up and shared my idea about how natural selection shaped aging to benefit the species. And they all just looked at each other and started grimacing and laughing. And they essentially said, you don't know anything about biology, do you? Natural selection can't shape traits that benefit the species. It only shapes traits to maximize gene transmission. I said, what? And they said, go get George Williams, 1957. And on the way home, I stopped by the library, mimeographed, photocopied a copy of that article, and it changed my whole career and my whole life. Because he explained why aging exists, that the same genes that make you age may give you benefits early in life. This is called antagonist pleiotropy. But that's not the only explanation. It's Also possible that if other things kill off all members of the species by a certain age, other mutations can creep in and natural selection can't do anything about it. So I spent that whole summer doing research, trying to look up life tables of animals in the wild and actually found very strong evidence that George Williams was right. I found that there was aging in the wild in certain species, varying a lot depending on what the species was, that could not be accounted for by mutations just creeping in because everybody died. They had to be accounted for by antagonistic selection, antagonistic pleiotropy. And this led me to collaborate with George Williams to write first a paper and then a book about evolutionary medicine. And so that's a good explanation. It's changed my life a little bit, understanding that. Because I think once you understand that aging isn't something, it's not a disease, it's not something you can fight, it's something that you might as well be appreciative that natural selection has given us all so much extra vigor early in life at the price of problems later in life. So I think that means we should appreciate good health when we have it and not fight too much. We should exercise and eat right, so we stay healthy as long as we can. But trying to fight and pretend that we are going to eliminate aging doesn't seem possible to me.

[Rob Wiblin]

Well, I think, I mean, some people draw the opposite conclusion from this because they'd say, look, it's not the case that it would be impossible to design a human species that lived much longer lives or conceivably didn't age at all. It would be possible. It's just that evolution hasn't happened to produce that result because of the circumstances in which we evolved. So maybe we just need to make some various modifications to get more replacement to generate the kinds of things that evolution would have prompted if there'd been less predation in the ancestral environment. And it would have been more beneficial to play long game.

[Randolph Nesse]

So Michael Rose is a wonderful biologist who studies aging at UC Irvine, and I appreciate his expertise on this. He's done fabulous work on flies and their aging, and he thinks that we will be able to expand human lifespan quite a ways. In particular, it seems to me, there may be a central trade off that's involved because our ability to fight infections and our ability to slow aging has a lot to do with the degree to which oxidative radicals are generated in our bodies. And mitochondria are responsible for generating those radicals. And the mitochondria have their own interests different from our interests. And it might be possible to do things that allow us to continue to have substantial vigor and control the actions of those radicals by drug or other means. But now we're way out of my area of expertise, and it's probably too late for my lifespan to hope for that. Doing too much good. And I think we should wrap up around about this point.

[Rob Wiblin]

Absolutely. All right. My guest today has been Randy Ness. Thanks so much for coming on the 80,000 Hours podcast, Randy.

[Randolph Nesse]

I really enjoyed talking with you, Rob. Look forward to hearing more another time.