Randolph Nesse: Many of the cases of depression I see in the clinic there's nothing useful about it and when my patients tell me, 'Oh, but doctor, isn't using drugs to treat my depression just covering over a useful response?' I say, 'No, your depression is not a useful response, we should stop it however we can, it's about as useful as chronic pain, it's about as useful as diarrhoea that causes you to become dehydrated and die—it's useless. On the other hand there are other patients for whom a different kind of conversation is more helpful and we must try to treat people as individuals, using our knowledge about what these emotions are for. And just think for a moment, most mental disorders are emotional disorders. Are psychiatrists carefully trained in the origins, functions and regulations of emotion as a proper physiological and functional foundation for understanding emotional disorders? No, they aren't, and it's not their fault either because basic science has not been there.

I do think from my clinical work, seeing thousands of patients with depression and anxiety that once I started taking a rigorous evolutionary view of this, and asking myself, is this person in a situation where they are pursuing a goal they can't reach and they can't give up—all of a sudden about half of my patients made sense to me.

Natasha Mitchell: All in the Mind on Radio National.Welcome, Natasha Mitchell with you. Now imagine a doctor's kitbag. Yes, there's a stethoscope. I can see a thermometer. A prescription pad. A bandage or two but hang on, what's this, a big book, it's certainly well thumbed, it's got that yellowed old book smell about it, I love that smell. There are notes scribbled down the edges of the pages in small, neat print. It's a copy of Charles Darwin's classic On the Origin of Species. It's 150 years since its publication this year which, of course, also marks the bicentenary of Darwin's birth, but what's it doing in a doctor's practical bag of tricks?

Well, this could be the bag of physician Randolpe Nesse. He's a professor of psychiatry and of psychology at the University of Michigan, and co-author of Why we Get Sick: The New Science of Darwinian Medicine, published in 1996.

He believes GPs ignore Darwin's theories to the peril of their doctoring and, with

acclaimed biologist George Williams, has developed the field of Darwinian medicine. And he joins me today—continuing Radio National's coverage of the Darwin Year.

Well, thanks for joining us on ABC Radio National this week.

Randolph Nesse: Lovely to be here.

Natasha Mitchell: Well, Randolph Nesse, you think modern medicine needs evolution. Do you think there's been a reluctance on behalf of doctors who are pragmatists at heart to adopt evolutionary theories in the thinking of their practice?

Randolph Nesse: You know your statement that doctors are pragmatists at heart is spot on. And I think it's a good thing, actually, we don't want doctors who just think theoretically about things, we want doctors doing whatever they think is going to be best for their patients. And I, too, as a practising physician, when I'm with my patient I want to see what can I do to help this individual now. None the less many doctors are also curious about why disease exists at all. We need not only an explanation about how it works, we also need an explanation about why the body is that way, that is, why did natural selection leave the appendix there given that so many people die of appendicitis? Why do we have wisdom teeth? Why are the coronary arteries so narrow? And why is the birth canal so narrow? And these questions, by many doctors, are dismissed as cocktail party conversation but they're not at all. Trying to understand why natural selection has left us vulnerable to disease turns out to be practically important.

Natasha Mitchell: Well what is the basis of Darwinian medicine, as it's being called, some people call it evolutionary medicine. I mean you really have been a trailblazer for 20 years in promulgating these theories.

Randolph Nesse: I've had the great privilege to work with George Williams, one of the leading evolutionary biologists of the 20th century, to try to find ways of applying evolution to medicine. When we began our work together, we first spent six months or so trying to figure out the evolutionary explanation for heart disease, for cancer, for arthritis. And only after thinking that together for months did we realise that we were asking the wrong question. Natural selection doesn't shape diseases, what natural selection shapes are vulnerabilities that make it so that we are likely to get a disease. That is, why are the wrist bones thinner so that they break when you fall forward; why didn't natural selection make them thicker?

These kinds of questions we realised had not been asked systematically, they hadn't been taken seriously. It's not just asking these questions about why the body is vulnerable, it's applying evolutionary thinking to genetics, it's applying evolutionary thinking to infectious disease, it's using phylogenetic methods to trace our own human origins and the origins of pathogens like E coli and HIV and that kind of thing. It's really bringing evolutionary biology to bear on problems of human health and public health.

Natasha Mitchell: I guess one of the accounts that people often have for why we see the persistence of diseases in human populations is partly that we're ageing, we are staying alive a lot longer than we ever did so our bodies are in a sense not sustaining ourselves.

Randolph Nesse: And of course that's quite right. In ancestral times not that many people lived that long. Although there's a big misconception at the heart of that: people say well the average lifespan is 35—they had the idea that people aged quickly and everyone died by age 40. That's not correct at all. If you lived until age 50 or 60 as a hunter/gatherer you were liable to keep on living, it's just that other things, infection, accidents, and warfare and the like tended to kill people off quite a lot faster.

But the question is, and the one that got me into this field, is why is there ageing at all? And I also realised if natural selection could help explain why ageing exists it might help explain all kinds of other things that seemed mysterious that are relevant to medicine.

Natasha Mitchell: You know the 19th century philosopher Herbert Spencer coined the phrase survival of the fittest and I guess it's been used and abused as a proxy for Darwinian thinking ever since. And I wonder if that's led us, including doctors, to equate the idea of natural selection with natural perfection. That somehow evolution surely crafts us to be the best that we can.

Randolph Nesse: Yes, Spencer's phrase,survival of the fittest, it's terribly unfortunate that that's become associated with Darwinism, because it's incorrect on several counts. The first important thing is that it's not survival that matters and of course what did he mean by fittest, exactly? The most competitive somehow or another. But that's not really the crucial thing for natural selection, the crucial thing is surviving and having offspring.

Now Spencer did give the idea, as many people have, that natural selection somehow has a goal and a direction and it creates things that are the best of all possible worlds. Some people have even misunderstood evolutionary approaches to medicine as suggesting that the body is perfect. But that's absolutely opposite as a real case: it's pretty obvious how you could use natural selection to find out why things do work but you can also use natural selection to figure out why things don't work very well.

Something like the appendix, for example, offers a very interesting example. Why on earth is this little tube of gut sticking off the ends of your intestines persist, given that so many people die of appendicitis? It could be that it's just a left over and it's gradually going away, but it kills a lot of people. Here's an idea, that there's a variation in the appendix, some people have a longer one and a skinnier one. Who's more likely to get appendicitis—the person with the larger, longer skinnier appendix or the person whose appendix is just fat and thick? Well it turns out what appendicitis is a swelling coming around the edge of the appendix and swelling it so it makes it like a balloon that blows up when bacteria grow in there, and if you have a small appendix you're more likely to get appendicitis and die and it's conceivable that natural selection is actually maintaining the appendix because people with a smaller, narrower appendix are more likely to die. And therefore people with a larger one persist more than others.

A very good example in natural selection not doing anything that's sensible at all but creating something and keeping something in the system that harms lots of us.

Natasha Mitchell: There are all sorts of interesting examples in medicine, lots of biological anomalies, it seems, but when you dig deep into possible evolutionary explanations you can come up with some interesting answers. Any others of the physical kind?

Randolph Nesse: There are hundreds of them and in fact it's important to note that Darwin was inspired in his studies in Cambridge by studying natural theology. There was a book by William Paley about understanding the details of the body as evidence for God's hand. And in his book he cited all kinds of observations in things that were really bizarre. For instance the path of the recurrent laryngeal nerve: it comes out of the back of your brain and goes all the way down around an artery in your chest and then it comes back up next to your windpipe, behind your thyroid gland and finally reaches your vocal cords— this is bizarre.

Or likewise the path of the vas deferens, which goes from your testicles and eventually out the penis— why not go direct, it's not that far—but in fact it goes all the way back through the pelvis, it's a very long tube, a silly design in both cases, things that take really senseless paths. Paley looked at things like that and he concluded that these must be evidence that the Creator wanted to put into the body things for scientists to observe, to notice, to be even more admiring of the amazing fact that anything worked at all.

Another really obvious one that everyone realises is the eye. We think of the eye as being perfect. of course. but think for a moment about the blind spot in the eye. What is it? The blind spot in the eye is where nerves and vessels come through the back of the eyeball making a place where you can't see. and then they spread out on the inside of the eyeball, getting between the light and the retina. Anyone who developed a digital camera with the wires going between the light and the film would be fired immediately. but we have an eye that is that bad. There are compensations that natural selection has created. For instance our eyes have a little tiny jiggle built in. If they didn't have that jiggle built in, the cells would not be able to continually respond to light, and shadows from the vessels would keep us from having a complete field of vision. So we have a jiggle built in and a chunk of brain that's designed to take the jiggle out so that it makes it look as if the world is one continuous scene in front of us.

The eye on the one had is incredibly perfect; on the other hand it's really a botched design—if you want to even call it a design. We really shouldn't be calling these things a design at all.

Natasha Mitchell: Well that's the thing; I mean how would you as an evolutionary biologist or a doctor think differently about the botched job of the eye from a creationist?

Randolph Nesse: I'm not sure what a creationist would say about the eye not being perfect at all. From an evolutionist's point of view there are all kinds of things that happen pretty much by accident, and the layer of cells that was initially was light sensitive in our ancestors way, way back, was different from those that became light sensitive in the octopus. And the octopus it turns out has an eye that is properly designed, so there's no blind spot, there can't be any retinal detachment, it's a complete field of vision—and how come they have a proper eye and we don't? Just bad luck, or good luck for them, depending on your perspective.

Natasha Mitchell: Randolph Nesse, you're interested in and have spent many years applying evolutionary thinking to illnesses of the mind, to mood, and I wonder how Darwin viewed emotions?

Randolph Nesse: You know he wrote this very famous book Evolution and the Emotions what was his exact title?

Natasha Mitchell: Expressions of Emotions in Man and Animals.

Randolph Nesse: That's right, which has been a great inspiration to many of us. His purpose in writing that book was to challenge the opinions of a fellow named Bell. Bell wanted to demonstrate that the many additional muscles in the human face demonstrated that we weren't related to other animals at all, that we were a separate creation. And again, this was part of a divine plan for us communicating.

Darwin wanted to prove that in fact we were very closely related to lots of other organisms: compared dogs and humans and monkeys and all the rest, and he showed not only did their faces move in similar ways but in response to somewhat similar circumstances. But his emphasis there was very much, we're the same as these other animals because we derived from common ancestors and therefore the brain and the muscles in the face, and the facial expressions all stayed somewhat the same. What he didn't emphasise was what good did it do to have facial expressions? What many people nowadays are asking is so why do we have emotions at all?

And I think the best way to think about that is that the emotions are really specialised modes of responding very much like your computer programs. If you want to make your computer work very well you load one program and it takes over all kinds of things, the keyboard, the screen, it makes them all work to do one task well because that's the task you're trying to do now. Well likewise the brain gets in to different modes of operation to cope with different kinds of circumstances. If indeed you're standing at your local watering hole, trying to get a drink and you hear a small grrr from behind a rock, that's not the time to be thinking loving thoughts about your partner, that's the time for you to very suddenly have a high heart rate, feel fearful, don't think about anything except where can I escape, where is there a tree.

Now this panic response or flight response is useful in that circumstance. And here is a newer view of emotions, we shouldn't be looking just for basic emotions in different chunks as if they are different cogs in a machine. We should be thinking of them as different patterns of responding that are useful in different circumstances. That is, each different emotion corresponds to some kind of situation that we've recurrently experienced—we. as a whole of species. over the last half million years or so.

So some circumstances are dangerous and those circumstances the emotion of anxiety is very useful. There are subtypes of anxiety, depending on whether the danger is from a wild animal, from another person, or from someone who is going to get mad at us in a social kind of situation. There's a number of different types of social types of anxiety and that's what I spend much of my professional life doing, is treating people who have too much anxiety.

Then there are other emotions. such as being with a loved one in a quiet. safe place. and in that case warm, overwhelming, loving feelings can be much more useful and in that circumstance a person who is flooded with anxiety is in very bad shape. The point is emotions aren't useful or unuseful in themselves, it depends everything on the situation.

Natasha Mitchell: My guest on All in the Mind is a founder of the field of Darwinian medicine, Professor Randolph Nesse. You're interested in the evolutionary function of negative emotions which are so often construed as being pathological or abnormal, too much negative emotion is a bad thing. Why do you think persistent, low states of mood, sadness, even depression might be adaptive, might have somehow been useful to us in terms of natural selection?

Randolph Nesse: Let's be clear, I don't think that persistent severe states of low mood are useful at all. I think they are pathology and I think we should do everything possible to treat them. But now you're going to want to know, so how do we tell when these states of low mood are pathology and when we're normal? And I have a sad answer there, we don't have the scientific foundation for making that decision. You know it's hard to see the benefits of negative emotions because they generally come up in bad times. Are there circumstances we can imagine where the best thing to do is nothing? Are there situations in life where the best thing is to be pessimistic, not optimistic? And I am thinking for instance my ancestors in Norway in the middle of a January winter, what about the ones who got very optimistic and decided to just go tramping off through the snow and the sub-zero cold because they thought they might find something. Now the smart thing to do in the midst of winter in northern Europe is to stay down, not eat too much, not be too enthusiastic about anything until there's a better time for being enthusiastic.

There's an important principle here, though, that applies to defences in general, all the body's responses that go off to protect us against different kinds of bad circumstances. Pain is one, fever is another, nausea, vomiting, diarrhoea, cough, fatigue and anxiety and low mood. Again coming back to pain—do you really want to have a body that never experiences pain? It seems like a good life, doesn't it, but there are people who are born without the capacity for pain and they quickly develop deformities, most of them die early in life and it's really not a good life at all to lack pain entirely. Likewise, what about people who lack anxiety at all; but do you really want to be without anxiety? I think there are people with these mental disorders, hypophobia Isaac Marks and I call them, I don't think they do well in life at all. They are on unemployment lines, they are in jail, they are in divorce court, they don't do well in life. On the other hand no one studies them because they don't come in and complain.

Then there's really abnormal pain, where the regulation mechanism's off and people experience pain even though there's no tissue damage whatsoever. A terrible, terrible medical problem. I think in the mood system it's exactly parallel, in chronic depression the normal useful low mood system, the deregulation is awry and we need to figure out why it is that certain people are especially prone in having that system be so poorly regulated. A bit principle here is what I call the smoke detector principle. This explains why so many of these phenomena occur too much, too often and too long.

So when do you want your smoke detector to go off? You could have a smoke detector that did not go off when you made toast. However that smoke detector also sometimes would not go off when there was a real fire. Because the cost of a false alarm in a smoke detector is very small, and the cost of a smoke detector not going off when there is a real fire could be fatal, we design smoke detectors so that they go off at the least hint of a fire, any little whiff of smoke. Well we should think about how natural selection has shaped the body's anxiety regulation mechanism, or the cough regulation mechanism, it's exactly the same principle. How expensive is it to have a cough, how expensive is one episode of vomiting, how expensive is it to have a bit of anxiety? Not very. How expensive is it not to have a cough, if you might be developing pneumonia? It could be fatal. To not vomit when there might be a toxin in you? It might be fatal. How expensive is it not to have a panic attack if that grrr-ing noise behind a rock might be a lion or a tiger? It could be fatal.

So as a result of this smoke detector principle, many of these negative emotions and negative feelings go off in circumstances where they are not actually needed and this is profoundly important for the general practice of medicine. Obviously you always try to figure out what's causing the problem the person is bringing to you, but a higher proportion of the problems are not diseases themselves, they are symptoms of diseases. That is it's pain, it's nausea, vomiting, a cough, fever, runny nose and a lot of what you do in general medicine is try to relieve suffering by stopping those responses.

Natasha Mitchell:

I mean if we think of low mood as an adaptation then, useful to us through evolutionary time, why are we then seeing so much low mood, so extreme situations of depression? Is it a sense that this low mood adaptation has become a maladaptation in our current environment, in our current social circumstances?

Randolph Nesse: Right, it's clearly being disregulated for some reason. I wish we had better data from the hunter/gatherer populations of how frequent rates of depression are. We cannot be confident that depression is much more common now although it seems likely. We do have good data, however, comparing it with the rates of depression in different countries and it varies eightfold depending where you are. At the very high, at the peak, is the United States of America where our rates are fully twice as high as most countries in Europe. However, if we go to Singapore or Taiwan rates of half again less than in Germany and the like. It could be something terribly physical, like the amount of exercise, and the amount of Omega 3 fatty acids people get. It could have something to do with people's sleep patterns, it could have to do with...

Natasha Mitchell: Social cohesion.

Randolph Nesse: Indeed.

Natasha Mitchell: Or failed expectations.

Randolph Nesse: Failed expectations gets very close to my best bet. which is what I would like to investigate more. If indeed pursuing unreachable goals and being unable to give them when you're not making any progress towards those goals is crucial towards causing low mood, and if it escalates to depression when you can't give up that goal.

Under some cultures in which many more people are engaged in pursuing some big life goal that they can't give up—oh my goodness, I see so many people in my practice back in the United States who are in exactly that circumstance. They've decided they wanted to be a rock star and nothing else will do in life and they've been doing it for 15 years now. I also see graduate students who have spent 4 or 5 years trying to get their graduate degree and they realise that they really don't like the field they are in and even if they did get their degree they would never get a proper job because there are no jobs in their particular area.

Depression in that circumstance is expected, or at least intense low mood. Let me make the connection between low mood and depression for a moment. When people are pursuing an unreachable goal, ordinary low mood makes you pull back and try to think about how else I can reach this goal and if different attempts to reach the goal don't work eventually it disengages motivation. So you pretty much give up on the goal and go on to something else. But there are many circumstances in life, especially for modern people, where you really can't give up the goal because there's no other exit, there's nothing else you can actually do. And in those circumstances ordinary low mood escalates into depression. I used to think from my earlier practice in medicine that I was always ready to encourage people to pursue what they were doing. If someone said I want to become a rock musician, I would say you can do it, you can do it, we can find a way. As I observe what's happened I see more often people once they can finally find an alternative way of living and give up things that aren't working, that's what really leads to remission of depression, is finding a way of life that is more satisfying and goals that we can pursue that are workable.

Natasha Mitchell: What do other psychiatrists make of your thinking around evolution and the purpose, the evolutionary purpose of low mood, of anxiety?

Randolph Nesse: Even 15 years ago they wondered what I was talking about, now when I give lectures to psychiatry departments they say oh yes, this makes great sense and in fact we need to be talking with our patients about the motivational structure of their lives and what they are trying to do. This is exactly what's going on, it's not just stress damaging the organism it's an adaptive response to what's going on in their lives and it helps also that I'm very aware that much depression really is a brain disease as well. We shouldn't just make generalisations about it all being caused within the individual and his or her chemical imbalance nor should we make a generalisation about it all coming from culture or from individual's problems in their living, it's different for different people.

Natasha Mitchell: You talk about gathering evidence over the years, what's been the most compelling evidence for you?

Randolph Nesse: For me personally, it's seeing thousands of patients.

Natasha Mitchell: That's not enough though is it, I mean that's one kind of data?

Randolph Nesse: That's right, although because these things are so personal, questionnaire data is not likely to get what we want to do. However, here's a quick summary of other kinds of things, Chuck Carver in particular is a psychologist whose done laboratory research showing that it is the rate of pursuit, the rate of approach towards a goal that influences mood more than what you get. Jutta Heckhausen is a psychologist from Germany who's now in California who has done studies of women as they move through life and a particularly a lovely study of women who wanted to have children but were unable to and were approaching menopause, and she watched as they became more and more depressed and then when they gave up the idea of wanting to have children their depression evaporated very, very quickly.

There's another scientist Kirsten Roche another Canadian psychologist who has very good data showing that people who have a greater tendency to persist in pursuing an unreachable goal compared with those who give up a little bit more easily. The people who persist more are more prone to depression than other people.

Natasha Mitchell: Saying all that though, is it then necessarily the case though that if people push through difficulties to reach a goal that was seemingly unattainable maybe that's worth it, maybe the peaks and troughs of mood that accompany that ambition is worth it?

Randolph Nesse: That's right, and I do not think that low mood is mainly to get you to give up; I think low mood is mainly to get you to pull back and think about a different way to get around the current obstacles. Or to just wait a time until there's a better time, I think it's a very subtle, sophisticated system that natural selection has shaped to regulate our mood so that we can put our efforts into enterprises that are likely on the average in the long run to pay off.

Natasha Mitchell: I mean in a sense you're saying that a period of low mood might allow us to be more cognisant of our situation, to reassess our situation, but low mood doesn't always trigger clear thinking.

Randolph Nesse: Actually it does trigger more accurate analytical thinking than positive states of mood. This is one of the most solid findings from social psychology of mood. It's quite different frames of mind: positive mood is more global and emotional; low mood people are more analytical and more careful and rational in their planning about the future. There's another lovely book by a woman named Emmy Gut, a Swedish psychoanalyst, called Productive and Unproductive Depression, where she goes into these ideas in substantial depth. And I think in the coming decade we're going to see lots more people taking these ideas and finding new and better ways to test them.

Natasha Mitchell: Randolph Nesse, it's been more than a decade since your book with George Williams came out called Evolution and Healing about Darwinian medicine, it was really written for a wider audience—and yet we're not really seeing evolutionary ideas being taken up in our GPs' surgeries—why not?

Randolph Nesse: I think actually the field is growing very rapidly now, but you're quite right, they are not growing within the field of medicine itself, and I've asked many medical school deans and physicians why this is. We want doctors to really understand the body, we want doctors to have basic science to make their decisions: genetics, pathology, anatomy...evolutionary biology is another basic science for medicine, it's one that has been neglected, and once doctors get the hang of it, once doctors recognise that this gives them a fundamentally deeper understanding of why the body is the way it is, they'll love it.

Natasha Mitchell: They might love it, but will it really change practice?

Randolph Nesse: Yes it will, I mean sometimes a doctor phones me up and says, 'I'm a Darwinian doctor, I treat all my patients with Darwinian principles.' And I reply, 'What on earth are you doing? Darwinian medicine doesn't tell you how to treat patients, it tells you what kind of questions to ask, what kind of research to do. So I'm very much against the idea that this is a method of practice, it's not at all, but it does tell you new kinds of studies to do on simple, simple things.

For instance, if you have a runny nose, is it good to use some kind of inhaler to block your runny nose? It depends, doesn't it, on whether the runny nose is more for the virus, which is trying to spread itself or whether it's more for you trying to empty out that virus from your nose, or whether it's both. How could you do this study? You could give some people a little salt water to inhale and some people something to inhale that would block their runny nose and see which ones get better faster. And as far as I know that simple, simple study has never been done, because people aren't really thinking in evolutionary terms.

Natasha Mitchell: Well Randolph Nesse, it's an intriguing field and a very interesting manifestation of Darwinian thinking 200 years after his birth. Thank you for joining us on the program.

Randolph Nesse: Thanks so much I've enjoyed talking with you.

Natasha Mitchell: Randolph Nesse, professor of psychiatry and of psychology at the University of Michigan, and his book is called Why we Get Sick: The New Science of Darwinian Medicine. Evolutionary theories really get some people's goat I know, I get the emails, so I invite you to let it rip, share your critiques and thoughts on the All in the Mind blog it's easy to post to and you'll find that along with the audio and transcripts via abc.net.au/rn/allinthemind. And we're on Twitter too.

Thanks this week to producer Anita Barraud, studio engineer Angie Grant, I'm Natasha Mitchell. Next week a critic's take on the neuroscience of adolescence.