Tonight, what I want to do is round off the series we've been talking about about uh human emotions, what are emotions, what's the biology of emotions, and particularly to ask this question, which is the more we learn about emotions, the more we know about the biology, the more potential we have to manipulate them. How might we do that and should we do that? So I'm gonna take a straw poll uh before we kick off. Those of you at home, feel free to join in, but I can't see your hands. Um, so who thinks the answer to this question is yes? And who thinks the answer is no? Oh, for those of you online who can't see that, there is a definite preponderance of no's in the audience. Uh, I have very bad news for you, all of you saying no. You might well be right, uh, but you are definitely not right, uh, because actually it's too late. We already do. We do this all the time. And the really bad news, those of you who've just told me we definitely should not do this, you've already done it. And in fact, you have been doing it since birth. Because I can almost guarantee that you have done this at some point in your life. And you have manipulated emotions in a way that is more powerful than anything that modern medicine can do. Because we are incredibly hardwired as a species to respond to this. We respond to the sound of infant tears, we respond to the sight. There's even quite a bit of evidence that we respond to the smell of tears with a very, very strong emotional response. Um, and in fact, what's amazing is we would respond like this even to infants that are completely unrelated to us, and we respond like this even if we don't have any infants. If you have no children, many of you in the audience won't have children yet, but you will still respond to that noise of an infant crying. And actually, your first response for most of us is to try and soothe them, right? Even if it's an unrelated baby. And I'm sure many of us have had that experience of being in a train and somebody's baby is crying, and it's really, really stressful, right? You're sat there thinking, that is emotional manipulation, right? And it is something that we have evolved to respond to because it's in our evolutionary interests, or particularly in the baby's evolutionary interests. We deliberately, subconsciously, but deliberately manipulate others' emotions for our own gain. We do it as children, we also do it as adults, and actually, um, there's quite an easy way to manipulate people's emotions. Uh, if we just do this and encroach very, very tightly on people's personal space, you start to manipulate people in the front row, like, oh, please don't come any further. Uh we're starting to manipulate people's emotions. We respond quite strongly to physical proximity. If it's someone we're attached to, it's quite a positive experience. If it's someone we don't know, it's a very negative experience. And we do that actually subconsciously, but but sort of deliberately in our day-to-day behavior. Many of us in a situation of conflict, for example, will either shy away or move towards someone, depending whether you're trying to tone down or ramp up the kind of rhetoric. Some people, politicians in particular, of course, are famous for using it. This is Lyndon Johnson having a delightful conversation in the middle of the civil rights era and disagreeing quite fundamentally, uh, quite rightly, of course, in this case, about pushing forward civil rights amendments. And as you can see, he's extremely close to his opponent here, Richard Russell, who, as people might know, is one of the last bastions of white supremacy in the southern states. Um, Lyndon Johnson making his point very vigorously by deliberately encroaching on physical space. And in fact, if we look at that quantitatively, we see that this has a very powerful impact on people's biology. So you can measure, as a first approximation, stress in people by measuring something called skin conductance, which essentially is a measure of how much you're kind of sweating, basically. Um it's a test that's used in things like lie detector tests, for example. The idea being if your skin conductance rises suddenly, you're under stress, you're pressured. Um, and so if you look at this graph here, what you see is a measure of stress, a measure of skin conductance. Um, when people are stood, volunteers are stood either close or further away. And the the unit doesn't matter. But the point is if you are close stood close to somebody up here, you're it's a stressful experience. Your stress response rises, and as the person standing moves further and further away, your stress response drops. And actually, intuitively, most of us know that. We've all had the experience, I suspect, of being at a party and someone's just that little bit too close, and it's a bit unpleasant. There's been some really fabulous work looking at this in kind of very real-world settings. Actually, one of the settings that lends itself beautifully to this is something that I'm sure many of us have just experienced, which is commuting on public transport. And public transport, of course, is a very non-biological, very uh unreal kind of way of transporting ourselves. If you think about human evolutionary time, it has been a very rare event when we have been packed into a small container together for a prolonged period of time. Today, in the modern Western world, many of us do this every day, but that doesn't mean it's not a stressful experience. There's been some very interesting work done, particularly in New York on the New York subway, uh, looking at the impact of that physical distancing on people's emotions. And one of the most interesting things I think they showed was that actually packing itself is not particularly a problem. So what they did was they monitored people traveling on the tube, and then when they got off, they asked if they would do a number of things to test their stress level. They looked at cortisol, so that's a hormone that rises when you're stressed in individuals, and they asked them to do a test that we quite often fail if we're under stress, which is to proofread a short document. Our proofreading skills get much worse if you're stressed, and many of us know that if you're trying to proofread something to a deadline. And what you see in that circumstance is if you look at people who've traveled in a very crowded carriage, they're actually no more stressed than people who've been in a relatively uncrowded carriage, most of us. But if you look at a relatively uncrowded carriage and look at people's seat positions, if you're sat in a seat and the seat next to you is unoccupied, your stress level is very normal. But if the seat next to you becomes occupied, your stress level after that journey rises because someone has broached your personal space when there wasn't actually really a need to, it wasn't that full. And so it's quite an interesting scenario, I think, where our emotions are responding to a kind of perceived threat. The idea that someone has sat next to us when they didn't have to, um, when there was plenty of space. Whereas in a situation like this, we're somehow able to turn off that emotional response because we recognize the fact that this is not intrinsically threatening, this is just a crowded tutor carriage. So emotional manipulation is happening actually all the time. Um, these are quite negative examples. None of us like hearing babies cry. Uh, most of us don't like having people come up really close to us and broach that kind of Freudian bubble. There are, of course, much more positive ways that emotions are manipulated, and one of the ones that is most bandied around in the kind of anecdotal uh press is the idea that smells may modulate our emotions. And I suspect that many of us uh in the room who might have had the experience of uh buying or selling property, for example, someone I almost guarantee you will have told you, or what you need to do before you have people come into your house, bake some bread, put the coffee on, because those smells that will help sell your house. Um, and it turns out that is actually true. I would caveat that by saying we don't know it's true for selling houses. So if you're an estate agent listening to this, don't change your plans. Um, but we do know it's true in other settings. And one of the nicest uh studies I have seen on this um is this one uh performed, where else in France, of course, um, using bakeries. And in this study, uh what people did was they monitored uh passers-by of different shops and they placed actors in the street, and the actor would walk past a shop and in front of the door would accidentally uh drop a glove. And then the people observing would look to see whether passers-by would go, stop! Oh, you've dropped your glove and pick it up, or ignore the fact. And it turns out that if you drop your glove in front of a nice smelling shop like a bakery, people are significantly more likely to stop you and give you a glove back than if you're in front of something like a pharmacy or a supermarket, which doesn't have those odors. So that positive odor is another way of emotionally manipulating people. So, top tip if you want to chill out at home, bake a bit more bread is a good strategy. So we manipulate emotions either deliberately or inadvertently, every day, all the time. The question is though, that sort of mostly kind of ticking along in the background, but should we actually do this in a more concerted way? And uh, you've already told me, many of you in the audience, that's a bad idea. We shouldn't manipulate emotions. And I can see a case for and I can see a case uh against. So let's think about the case for first. The case for emotional manipulation, I think, is actually, in some ways, quite a compelling healthcare case. Um, so this, for example, uh is a graph in the UK of the number of recorded hate crimes over time, and you'll see this very depressing uh fact that the graph is going up and up and up. It's a slight hint of positivity that it's fallen ever so slightly in recent years. But the number of hate crimes recorded still in the UK up towards about 150,000. That's a lot of hate crimes. And, you know, big caveat here: hate crime is clearly not just about emotions, there's a lot here, but there is, by definition, an emotional component to this. Somebody hates somebody else for being the wrong colour, the wrong religion, the wrong sexuality, whatever it is, and they commit a crime. So there's a case to argue, I think, that if you could somehow manipulate that, and we've talked in a previous lecture about how you might do that, you could reduce this number, and that would have a clearly a major benefit for society, and not least for the people who are the victims of hate crime. So we could manipulate emotions to benefit others. We could also, of course, manipulate emotions to benefit people themselves. And clearly the biggest place where there is potential there is in mental health. Roughly one in four of us will have a significant mental health problem during our life. That's a very, very large number. Um, if we are able to intervene either before or during to change our emotions in a way that might help head that off, the potential benefit to individuals and to society at large, I think, is huge. So I would argue that understanding more about emotions in a way that might help you intervene has quite a big societal potential. The flip side, of course, is that a big potential is not immune to being misused. And unfortunately, history is full of examples of people who are really good at manipulating emotions for all the wrong reasons, not least uh like the rise of Nazis in Nazi Germany, obviously, but many other dictators who have proven themselves to be exceptionally good at harnessing people's emotions and manipulating them, either through kind of massive crowd control, um the ability to unite people around what is apparently a common foe, uh, or to sow kind of anarchy in a sort of uh destabilizing way by manipulating people's emotions. On an individual level, we know that emotional manipulation has a huge cost, particularly uh in the setting of domestic abuse, of course. This is Macbeth, uh slightly uh older version, but nonetheless, this idea of emotional manipulation by one partner of another, uh, and it might be romantic partners, it might be parents and children, there are lots of places where emotional manipulation happens deliberately to the detriment of at least one other person. And so there's an equally potent argument to say manipulating emotions is a dangerous thing to do. And so I think as with most things in medicine, uh there is a balance here between what you might want to do and what you should be allowed to do. So, that notwithstanding, there is still a case, I think, even if your judgment is that you would never want to do this, understanding how you might might be a safeguard against preventing others from doing it. So, uh, what I'd like to turn to now is to think about how we might manipulate emotions kind of biologically. And of course, this is not unique to this lecture, it's not new, it's not a new idea at all. Uh, a large chunk of the pharmaceutical industry has been working out how to manipulate emotions for the last hundred years, pretty much. And in some ways, we've got pretty good at it, and in other ways, actually, it's been really, really slow. And there are nowadays many ways that you can apparently manipulate emotions uh using a bottle of pills or liquid or whatever. One of the most commonly done ways to manipulate emotions, of course, is uh with the group of drugs that are known as mood stabilizers. And so mood stabilizers do sort of what they say on the tin. They are not imposing an emotion, they're not transforming you to be happy if you were sad or sad if you were happy. What they are doing is preventing the most extreme experiences of emotion, usually in both directions. And so one of the challenges of mood stabilizing drugs is that they might prevent you being massively depressed, but they generally also prevent you being massively happy. And so there is a kind of trimming of the edges of your experience. Those kind of drugs include things that we have known about for a very long time. So top right here is lithium, lithium carbonate in this case. Lithium is a drug that we have been using for well over 50 years in the treatment of bipolar and schizophrenia. Interestingly, despite its incredibly long history, we still have no idea how it works. But it does work in some patients some of the time quite well to reduce, particularly the very, very deep depression that some people experience with those conditions. Down the bottom, a much more recent drug, lumotrogen, uh, which is uh used similarly to kind of trim off those edges of emotional experience. Um, and I think this is a very interesting drug because it tells us a little bit about how this emotional process is working. So the function of lomotrogene essentially is to reduce the amount of release of particular neurotransmitters. It's not blocking anything, it's just kind of decelerating the reduce, the release of things like glutinate, which are neurotransmitters that control mood in some cases. So the reason these drugs work to stabilize mood is because they're kind of just limiting the kind of accelerator pedal you have in your brain. So you can still accelerate, but not as fast and not as slow as you might otherwise have done. Mood stabilizers have been transformative in some ways for mental health, and they have undoubtedly helped millions of people with those conditions. But one of the big challenges we still have is that they don't work for everyone all the time. Um, and sometimes they work for people and then they stop working, and vice versa. We don't really understand that. So I would argue there is still a long way to go in understanding how we might improve the chemistry of these drugs to really help people with these conditions, and of course, think about what it tells us about the underlying reasons for the condition in the first place and how we might address that in a more permanent way than simply uh adding pharmacological agents. So, mood stabilizers are one set of drugs, are in some ways they're not actually emotionally manipulating, they're trimming the extent of our normal emotions, but they're not imposing an emotion. A second class, which is perhaps more arguably likely to really impact on emotions, are antidepressants. Okay, again, huge drug class, millions of people worldwide take antidepressants. Um, they come in different flavors, they do different things. Uh, you have ones like Certrilline here, uh, which is belongs to this class called a selective serotonin re-uptake inhibitor, which is a real mouthful, good scrabble word. Um, and and this uh drug works, as it says, to prevent the reuptake of serotonin. And so for those of you who uh don't remember your GCSE uh neuroscience, uh, what you have in your brain and indeed through your nervous system are different nerve cells talking to each other. And so you have one nerve cell here and another one here. To cross the gap between them, what they do is they release neurotransmitters. So nerve one releases neurotransmitters, they diffuse across what's called the synaptic gap, and the new nerve picks it up and propagates the signal onwards. And so that neurotransmission between the gap is critical to all of our nervous processes. Clearly, there's a problem here. If nerve one releases a neurotransmitter and signals to nerve two, that neurotransmitter is still sitting there, still signaling, and so you can't turn the signal off. And so what the brain has, and indeed the whole nervous system, is a very complex set of enzymes that are removing the neurotransmitter from the gap all the time. So that once you've issued your signal, it is then shut down and you don't end up permanently signaling. And actually, one interesting side effect is that the story is that many potent neurotoxins, one of the most dangerous molecules we know of, work by stopping that re-uptake. So they don't actually block nervous signaling, they keep it locked on the whole time. Anyway, uh these drugs are what they're doing is they are slowing that process of neurotransmitter removal. And so when your signal comes across, uh it is perpetuated for longer. And because serotonin is generally associated with positive emotion signals, by preventing its reuptake or slowing its reuptake, you increase the overall level of positive mood in the brain. You can do that in a different way. So, for example, that we also have enzymes like this one here, which is which are designed to degrade neurotransmitters, and so other drugs that we have block these enzymes to slow the degradation. But broadly speaking, most antidepressants work in the same way. They are preventing either the degradation or the reuptake of neurotransmitters as efficiently as would otherwise happen. So they are overall increasing the level of those neurotransmitters in the brain. And so that's important for two reasons. It's important because it helps enhance mood, because you're kind of overall raising the level of this positive neurotransmitter. But it also highlights one of the problems, which is over time the brain starts to adapt. It gets used to this new higher level of serotonin. And so one of the problems with these drugs is that you can grow tolerant to them because you're used to your body has reset this new level and eventually they no longer work anywhere. So that's quite a big challenge for psychiatry. So this is a group of drugs which do influence emotion, they're kind of changing overall positive mood. Again, they work in some people, not in others, some of the time, not all the time. Lots to do still on those. And then the final group of drugs, which I think are very interesting in thinking about emotions, are the ones which really go all out. So we have this first group that I've talked about, mood stabilizers, they're kind of tweaking the edges. This group, a little bit more potent, they're upping the overall level of serotonin. And then you have this group, the psychoactive drugs, and they go wild. Um, not for no reason are they called psychoactive because they do pretty crazy stuff to your brain. Um, and actually, largely at the moment, these are not used medically, they're of course used illegally, typically as recreational drugs, uh, lots of risks associated with them. So please, this is not in any way a suggestion of trying them. Um but they do lots of interesting things biochemically to the brain. So you have groups called enactogens, which are there to, which whose function, if you like, is to stimulate, really stimulate the brain big time. So this one up in the top corner, MDMA, more commonly known as ecstasy. Um ecstasy is a drug that is very, very dramatically influencing your emotions. It is essentially driving your brain into overdrive, and you flood the system with generally positive neurotransmitters like serotonin or dopamine. And that is, of course, why it's called ecstasy. The idea is apparently, if you take it, that you feel these euphoric uh moments of great pleasure because suddenly there's a surge of positive neurotransmitter in the brain. That might sound ostensibly quite good, has lots of risky side effects, it increases heart rate, increases temperature. Actually, quite a lot of people die uh from ecstasy overdose because they overheat and become uh firmly unstable. Um, and the other big risk with these is extensive use, just like any other drug, resets your body's physiology to be tolerant to that high level. And so what you find in long-term users of ecstasy, if they survive, uh, is that their body has reset to expect a much higher level of neurotransmission. Consequently, when they're not taking ecstasy, they enter a kind of depressive state because their normal state for the neurotransmitter is now much higher than the rest of ours. So lots and lots of risks here. And finally, in the psychoactive drugs, you have drugs that really impact so dramatically that they don't just change your mood, they change your whole perception. These psychoactive drugs, um, so here, for example, the hallucinogens are like psilocybin, this is the active ingredient in magic mushrooms. Um, and magic mushrooms and all the related compounds uh do everything and more. They are fast tracking your neurotransmitters, you're experiencing all these strong emotions, but they're also short-circuiting things like your optical circuits, so you start to hallucinate and hear things and all sorts of weird and wonderful things. Uh, and for that reason, they are very tightly controlled, they're very dangerous drugs. However, there is some positive potential here because there is some quite active work at the moment in clinical trials looking at these drugs as treatment for some of our most destabilizing emotional conditions. And in particular, the one which is under active investigation is post-traumatic stress disorder. So PTSD is known to lead to quite a strong emotional imbalance in people, often associated with depression, long-term depression, anxiety. Um, and there is some tantalizing early data that used very tightly under medical uh advice, generally in low dose, drugs like psilocybin might actually help to reset the brain and break people out of PTSD and related uh disorders. And so I think there is a case here to think about whether selective manipulation of emotions, perhaps for a short period of time, might have a very long term benefit to people. So there's quite a lot that we can do drug wise in emotions, some of which we understand well, some of which we don't understand at all. That offers, I think, massive potential medical benefit. There are lots of things we've talked already about the impact of mental health. There's a lot of stuff where we can make big impacts. But there are also a lot of places where there is huge risk here. And unfortunately, as with all things, history has shown us that. So some of these compounds, for example, were actively worked on by military scientists, even in allegedly progressive nations like the UK and the US back in the 50s and 60s, either for interrogation of prisoners or for dosing their own soldiers, for example, to enable them to fight and combat for longer periods, or potentially to protect them against the consequences of things like PTSD. And I think therein lies a real ethical challenge. So on the one hand, you could argue that preventing a soldier from having PTSD is clearly a good thing. We don't want anyone to have PTSD. And so being able to dose people with something that kind of immunizes them against it is a positive thing. On the other hand, if that then enables those soldiers to do things they wouldn't have done otherwise or to enter combat zones they wouldn't have been able to deal with, is that truly a benefit to society, even if it's a benefit to the individual? So lots of ethical minefields, I think, in terms of how you use these compounds in individual people and what the what the right choice is. So there's a lot that we can do pharmacologically, a lot we can do chemically, lots of risk, lots of potential benefit. What I want to think about now, though, is a different aspect. And that is, I've been talking a lot in all of my lectures actually about how we can learn a huge amount, I think, from biology. And we can learn quite a lot from biology here too, because people have thought for a long time about this idea of biological manipulation of emotions, usually not by a little green alien in your head, but nonetheless. And actually, this idea of things living in our brains or our guts or whatever and manipulating our behavior is a real kind of mainstay of science fiction, right? I'm sure many of you have seen Last of Us or all these zombie movies where some kind of weird thing comes from outer space, takes over our brains, and suddenly we all start behaving differently. And actually, that is not entirely science fiction. There are quite a lot of examples of biology manipulating people's emotions, or at least other animals' emotions. One of the most uh sort of spectacular examples, which is close to my heart because my background, as some of you know, is an infectious disease, is this delightful fungus called cordyceps. And so cordyceps is a big group of fungi, actually, which parasitize on invertebrates, insects primarily. Um, and the fungus, which is this huge thing growing out in the back of the neck of this unfortunate ant, um, is a master of biological manipulation. So the spores of a fungus enter its particular host, like an ant, but through scavenging. They germinate inside the ant and they grow inside the ant and eventually they will sporulate and spread their spores on again. But they have a problem, right? If they kill that ant on the forest floor, the spores that will arise from it are not going to travel very far. That fungus is not going to get very far at all. And so what the fungus has evolved to do is a really spectacular bit of manipulation. It grows inside the ant for a few days, and then, in a way that we still don't understand, it suddenly changes the behavior of the ant such that the ant will climb the nearest available tree, it will latch on with its jaws, you can see that on top, and then it will die. The fungus continues to grow, it comes out of the ant and it sporulates, and now it's a couple of meters up into the rainforest, it can spread its spores over a much, much wider area and be much more successful. So this is a fungus that is manipulating the behavior of the ant quite precisely. Now we don't know very much about the emotions of an ant, and I guess we could probably place some money there. It's probably not a very deep emotional life that your average ant has. Maybe I'm doing the medic, but either way. So we don't know whether the ant is kind of migrating up a tree because it's super happy or it's super sad or it's just doesn't know what it's doing. Um, but nonetheless, this is kind of neurochemical manipulation of an animal by a fungus. These kind of behavioral manipulations are actually surprisingly common in infectious disease. So one of the most obvious ones that we have known about for hundreds of years is a viral manipulator, which is rabies. All right, so rabies, as people will probably know, uh one of the most dramatic symptoms of rabies is that infected animals, including ourselves, uh become extremely aggressive. We tend to salivate a lot, we froth at the mouth, uh, we become very anxious and actively aggressive. And so, you know, rabi dogs fighting is a common sight in areas of the world where rabies is still endemic. The virus is not doing this just to be difficult, it's doing it because the virus is transmitted through blood and through saliva. And so if you are a virus that encourages your host to bite other people, you are a really successful virus at spreading. And so this is a very simple organism, right? The virus only has 10 or 12 genes, but is able to manipulate a very advanced animal, like a human or a dog, into doing something it wouldn't normally do, like biting other people. It does that actually by acting in a very similar way to those drugs we were just talking about. So, what the virus is doing, in fact, is lowering serotonin in the brain. So I just said earlier that elevating serotonin makes you feel happy, that's how antidepressants work. Lowering serotonin makes you feel anxious and angry, and so the virus is actively reducing your serotonin to cause those effects in its host and to get itself spread. Very simple bit of biology, doing some very elegant emotional manipulation. But I think the biggest master still at the moment that we know of in the biological world for emotional manipulation is actually a parasite. And some of you, if you came from all those years ago to my first uh series of lectures, will have heard this before. Um but this parasite Toxoplasma Gondi is still, I would say, the most uh famous, the most best understood uh manipulator of human behavior. This is a parasite very loosely related to malaria parasites. Um it is found all across the world, including in the UK. And its normal lifestyle is to live inside rodents. Uh, it happily replicates inside rodents, but it cannot complete its life cycle. To complete its life cycle, it needs to get from a rodent into a feline. Um, and as we know, uh, although cats like mice, as you can see here, that's the only joke you're getting tonight. Um, cats like mice, mice do not like cats. And so that the parasite has a problem. It has to get from its mouse or rat host into its feline host to complete its life cycle. To do that, it has a neat trick up its sleeve, which is it tells the infected mouse that its time as a scary prey item has gone. And this is the moment mouse to be brave and to do very unwise things like hang around cats. Um, and so what you see in infected mice, for example, hopefully it's gonna work here. So uh there we go. This is an infected mouse. And what you see normally, those of you who've met a mouse, um, mice hide in corners, they don't like bright lights, they definitely don't run around the middle of a big, well-lit box going, hello. Um, and this is because this mouse has a toxoplasma parasite within it. The parasite is encouraging the mouse to be awfully brave, deliberately, so that out in the wild, that mouse is gonna sooner or later meet its fate at the hands of a cat, allowing the parasite to complete its life cycle. Very neat bit of emotional manipulation by a parasite, right? Why am I telling you this, uh, unless you're a cat lover, not that important. Turns out to be quite important, because toxoplasma doesn't just live in cats and humans, cats and uh rodents, it also finds its way into us. We are a dead-end host. Most of us happily do not end our days by being eaten by a cat. I guess there are some exceptions, but most of us won't. So to the parasite, actually, uh, we are end of the line, but it doesn't know that, of course. So when the parasite enters humans, which it does with alarming regularity, it essentially tries to behave in us as if we were a mouse or a rat, which for many of us is you know quite genetically similar. Um, and so uh if you look in people, uh, what you quite often see is that many of us carry this parasite either in muscle tissue or quite often in the brain, actually. So, this is a classic example here. In this MRI scan of someone's brain, you can see the white sort of circle on the left of the screen. Um, that is a classic parasite lesion. This person in the image didn't know they had toxoplasma at all. In fact, they had a road traffic accident. The MRI was to check they didn't have a bleed on the brain, um, but they revealed a parasite there. Uh, and in fact, many of us uh in this room will have this experience. Up in the UK, we estimate about one in three people is infected with the parasite. Um so this is your moment to look to your left and look to your right and work out which one's got it. Uh and we never know, most of us never know. Because the dogma is that this is completely asymptomatic. Except it turns out to be not entirely asymptomatic. If you carry a latent uh toxoplasma, you are unfortunately significantly more likely to suffer from certain mental uh illnesses, particularly schizophrenia. But perhaps more interesting, I think, when you think about emotional manipulation, is you are more likely to indulge in risk-taking behaviors. So if you have the parasite, you are twice as likely to crash your car than if you don't have the parasite, particularly in crashes that involve uh taking a risk, running a red light, driving too fast, those kind of things. Um on a much more positive note, if you harbour the parasite, you are much more likely to open your own business. There you go. Uh so if you're someone listening to this thinking, I've got my own business, then I, you know, go for an MRI scan. Um uh so that so and the the theory here is that opening your own business is risky, right? You might go bankrupt. Um, and so you take the risk, um, and consequently, the parasite has been influencing you just like in the mouse to take a gamble, to be a bit risky. Unsurprisingly, you've taken the risk, and the problem with taking risks is they don't always work out. So if you have the parasite, you're also twice as likely to go bankrupt as the rest of us. So uh benefits, costs, you know, one way or the other. Either way, the important point here, I think, is that a microscopic parasite that you don't know you have is apparently manipulating your emotional life and actually some quite big life choices about starting companies, for example. So, chemistry can alter emotions, biology definitely can. Uh, the question is: can we harness this, and if we can, should we, to really start to control human emotions? Can we come up with a kind of remote control emotional uh system? And of course, there is a huge amount of interest in the potential this holds, uh, not least in this field of brain-computer interfaces. So, this idea that we may be able to develop tools that allow us to directly plug into the human brain an interface, as it says, between computers and the brain. The best example of this, of course, is the Neuralink Company, Elon Musk's company, but there are many others that are developing systems that will sit inside the human brain initially for very, very specific tasks. So Neuralink is shown up here on the top right, it's a sort of coin-sized uh um device, and you probably can't quite see, but dangling down from it has these microscopic threads that are sewn actually into the brain. And one of the most interesting things that, I mean, the device is amazing, but one of the most interesting parts of it, I think, is also the process of implanting it. So humans can't do this, it's far too fine. And so uh this robot that you see here is a robotic surgeon, and it sews the threads into the brain of the person receiving it with incredible accuracy, far better than any human can. So far, Neuralink has been used to try and restore functions to people who have very serious brain conditions. So there's been work, for example, on restoring sight to people who are blind, um, to interpreting speech from people who can no longer speak because of diseases like lateral sclerosis. A lot of huge medical potential here. But the underlying aim of Neuralink and all many companies uh like it is actually to extend this beyond normal human experience. And so it's a very clear statement that they are keen to ultimately move towards a system where, for instance, we might be able to uh automatically interface with the internet, and actually all of us would know everything all the time because it's kind of plugged into our brain, which is quite a long way away, I think, if ever. But probably between now and then, there will be a point at which our understanding of biological emotions might allow us to use devices like this to manipulate that. I think there's a really big question there about how we should do that, should we do it at all, who would be allowed to do it, who would not be allowed to do it, and what's the extent to which you should be able to use your emotions. You know, should you be able to kind of press the button to make yourself super happy every single day of your life? Um, and what does that mean for our understanding of what who are we? You know, what is our experience if actually our emotions are being driven by an implanted device? Happily, perhaps we don't have to worry about that quite yet, we're somewhere away from uh any of these devices being able to achieve that. Um but uh for my final couple of minutes, I want to tell you about a much, much easier way. If you're sitting there thinking, this sounds great, I can't wait to manipulate my moods, bring it on, stick something in my brain, I'm there. Um the good news is you can do it in a much easier way than having open brain surgery. Um, happily. Uh, you can do mood manipulation the really easy way. And the easiest way you can start straight away when you go home, or maybe you can do it right now if you're listening online, uh, by changing your diet. Uh dead easy. Not quite as glamorous, I have to say, as having brain surgery, um, but uh quite a promising route through to mood manipulation. Why is that? Uh and I don't mean, I mean, that's also true, but you know, a glass of red wine and a bar of chocolate is pretty good for mood too, but that's not quite what I mean. It's not about comfort eating. What I mean is if you fundamentally change your dietary intake, there is quite good evidence that it will affect your mood. And it's doing that, of course, because of my favourite topic of all time, uh, which is the human microbiome. Those of you who've been to any of my lectures before will know I can't resist talking about the microbiome. And if you haven't been before, bad luck, I'm gonna bore you about it now. Um, we have, along with most other species, an incredibly rich and still very poorly understood set of organisms within us for our entire life. About 30-ish trillion bacteria currently residing in your intestine. That is far more bacteria than you have human cells. Uh, you are a walking zoo of interesting microbes. Uh, we still, despite all the advances in genetics and genomics, we still know a reasonable amount, a reasonable amount, about only maybe 10% of those species. The rest is a black box. We know they're there, we can see their DNA, don't we know what they do? Um, and we know increasingly uh that they are impacting on pretty much every aspect of our life, including mood. Uh, and that has been known anecdotally for some time, but we have not really understood why different diets and different microbiomes seem to impact our mood. And now we do, and we understand quite a bit more because it turns out that many of those bacterial species in your gut are either producing or breaking down human neurotransmitters. And in fact, there are loads. So in this table, you can see a whole variety of neurotransmitters in green on the left hand side that are produced by a particular bacteria we find in the human gut, and on the right hand side we see a set that are broken down by bacteria. And the sharp-eyed amongst you will notice that some of those are the same on both sides, which means, for example, if you look at something like serotonin, that's the neurotransmitter we were talking about being associated with positive mood earlier, depending on how many of which group of bacteria you have, you'll either be a net producer or a net consumer of serotonin in the gut. You might say, well, why do I care? That's in the gut, that's a long way away. But your gut, of course, is one of the most nervously dense parts of your body. There are millions and millions of nerve cells that are interwoven into the lining of your intestine and are able to pick up these neurotransmitters. And we now know there is a very strong brain-gut axis. And so they can communicate that signal directly back to the brain. And so, actually, it's entirely feasible, I think probably almost guaranteed, that the metabolic production or breakdown of neurotransmitters in the gut is directly impacting on the mood you experience in your brain. And so, literally, in some ways, you could eat your way happy or eat your way sad. Uh, because if we could kind of figure out which foods encourage, for example, the serotonin-producing bacteria, you might be able to boost those, make yourself some more serotonin and feel a lot happier. And so, actually, this is probably an explanation for some of the anecdotal stuff people talk about when they say things like, oh, I can't eat cheese after nine o'clock because I feel so depressed. You know, that's actually perhaps not spurious. That might be true for those individuals. And similarly, when people say, and if I don't get my, I don't know, my porridge oats in the morning, I feel so gloomy. You know, that may also be true. The porridge oats are feeding your bacteria that make serotonin and make you feel happy. So if we can get the balance right, you might be able to manipulate your mood for benefit without ever having to open the top of the skull and wire something in, which is encouraging. We know relatively little about how to achieve this uh through experimental manipulation, and most of what we currently know is based on uh animal studies. But actually, in animal studies, it is showing really quite a lot of promise. So in our favorite uh laboratory animal, the mouse, for example, you can strongly influence mood by manipulating the microbiome. So if you take typical mice, as people will know, mice are generally quite timid creatures. Um, and if you raise a mouse in the lab, it will be relatively scared of light and noises and people and all those kind of things. If you raise that animal in a completely sterile environment where it has no microbiome, which you can do in a laboratory setting, so you uh the mouse is born through cesarean section, is kept sterile, it never gets colonized back to bacteria and it has no microbiome, that mouse is significantly more anxious and shows behaviors associated with depression than a mouse that is genetically identical but has a microbiome. And then if you take that anxious mouse with no microbiome and you seed it with an active kind of probiotic type mix that populates its gut with particularly beneficial bacteria, you can create that mouse into a mouse that is not just less anxious than it was before, but is much less anxious than other mice, and in fact is perhaps unwisely brave in sudden departments. And so, at least in mice, you can really change the behavior of a mouse between anxiety and bravery depending on what's in its microbiome. Um, we're at a very, very early stage of understanding that in humans, but there is quite a bit of promising data emerging. Some of that data is coming from people who have received fecal transplants. So you might be aware this is something that is now done relatively widely around the world for particular conditions, especially people who've had uh really untreatable C. diffacyl infections, a bacterial infection. One way to try and treat that is to give people very, very extensive antibiotics, remove all their bacteria, and then recolonize them with the microbiome from a healthy donor. So you take feces from a healthy person, you transfer them into the person who's been suffering with uh C. diff. And if you're lucky, those healthy bacteria will grow, populate the gut, and make it much less likely to get C. diff infected. At least anecdotally, some people who've had that uh experience then say their their emotional state has changed afterwards. Clearly, quite a lot of that is going to be about the fact they feel a lot better. Um, but actually, you can kind of control for that and show some evidence that that transplant may also be modulating the emotional state of those individuals based on the bacteria they have. Much more uh, I think, potently and quite excitingly has been the work that's recently and still very much ongoing in terms of randomized trials in people suffering, particularly with depression. And there is now quite an extensive evidence base showing that you can have moderate, you know, not transformative, but nonetheless existingly significant improvement in mood by altering uh diet of people with depression and anxiety, and in particular by giving them specific combinations of probiotics. Um there have been about 10 or 15 different trials using either individual bacteria, groups of bacteria, bacteria in association with particular foods, um, most of which have shown uh a significant improvement in symptoms who have had these probiotics after the course of the uh of the dosing. It's not a perfect fix. You know, I'm not by any means saying we're gonna end all mental health problems, but I think you know, if we're able to even incrementally change depression rates by something as simple as giving people a different yogurt for breakfast, there is a lot of medical potential there, which I think is really exciting. And finally, then we might be able to manipulate your mood and change your life and perhaps even treat your depression with the probiotic. Um, but what does this mean for our sense of who we are? Most of us, I think, if we ask ourselves in the street, you know, if I ask any of you, are you generally a happy person or a bit gloomy? Are you a pint half full or pint half empty? We all know that for ourselves, right? Oh, yeah, I'm a I'm always an optimist. And the question becomes: is it really you? Or actually is that your microbiome you're reflecting? And there have been a couple of recent studies which really suggest that at least some of it might actually not be you. Um, fascinating study quite recently from Oxford, looking at healthy volunteers who were asked to complete a quite detailed questionnaire which analyses personality traits, and it's looking for things like uh neuroticism or outgoingness and these kind of things. And then analyzing the fecal microbiome of those donors, so donated feces that were sequenced and the abundance of particular bacteria was looked at. And what you see is that for some traits, like sociability at the top, for example, there are particularly particular species of bacteria that are positively correlated with it. So if you're a sociable person, you're much more likely to have more acamansia, a particular bacterial species, than if you're someone who likes to kind of hide with the book on a Friday night. Um, uh that's clearly correlation, not causation, but at least suggests that uh there is the possibility that whether or not you decide to stay in on a Friday night or go out partying uh might not have to be your decision, but might be the decision of the bacteria inside your gut. Um and perhaps the most uh interesting and slightly disturbing one, I think, is very recent work looking at uh traits that we associate with functioning in a professional environment. So like conscientiousness. And it turns out there are particular bacterial species in your gut that are associated with either being more or less conscientious person. So, for example, you can see two species here going in opposite directions. Uh so if you have this one down the bottom, you're much more likely to be conscientious. If you have the species up the top, the more of it you have, the less conscientious you are. Um, and I think when you think about what that means, that is actually quite fascinating because it sort of suggests that something that we think of being a very, very human, how diligent am I, how dedicated to my job am I, might actually be not about you, but about the particular bacteria in your gut and therefore perhaps even what you had for breakfast. The positive spin of which means that the next time you're in a job interview and finding yourself really, really struggling, take a pause before doing your conscientiousness test, have a bowl of yogurt, um, and uh wish yourself some luck. Thank you very much indeed for listening.