Gresham College Lectures

How Microbes Manipulate Life

April 03, 2023 Gresham College
How Microbes Manipulate Life
Gresham College Lectures
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Gresham College Lectures
How Microbes Manipulate Life
Apr 03, 2023
Gresham College

Every animal on the planet carries with it an astonishingly diverse microbial zoo – millions of invisible organisms that thrive on the skin and in the gut. They play an important role in health and disease and may also shape human emotions and behaviour. Viruses may stimulate aggression, parasites can trigger suicide and bacteria can block fear responses. 

The evidence for our interaction with microbes may even make us want to re-evaluate the concept of free-will.

A lecture by Robin May recorded on 22 March 2023 at Barnard's Inn Hall, London.

The transcript and downloadable versions of the lecture are available from the Gresham College website:

Gresham College has offered free public lectures for over 400 years, thanks to the generosity of our supporters. There are currently over 2,500 lectures free to access. We believe that everyone should have the opportunity to learn from some of the greatest minds. To support Gresham's mission, please consider making a donation:


Support the Show.

Show Notes Transcript

Every animal on the planet carries with it an astonishingly diverse microbial zoo – millions of invisible organisms that thrive on the skin and in the gut. They play an important role in health and disease and may also shape human emotions and behaviour. Viruses may stimulate aggression, parasites can trigger suicide and bacteria can block fear responses. 

The evidence for our interaction with microbes may even make us want to re-evaluate the concept of free-will.

A lecture by Robin May recorded on 22 March 2023 at Barnard's Inn Hall, London.

The transcript and downloadable versions of the lecture are available from the Gresham College website:

Gresham College has offered free public lectures for over 400 years, thanks to the generosity of our supporters. There are currently over 2,500 lectures free to access. We believe that everyone should have the opportunity to learn from some of the greatest minds. To support Gresham's mission, please consider making a donation:


Support the Show.

Speaker 1 (00:04):
So tonight, uh, for this lecture, what I'm hoping to do is convince you that although you think you came here out of your own free will, actually, free will is a bit of an illusion. Um, and many of the things we do are maybe not quite as much in our possession, um, as, as we thought. This is also partly an excuse if you get up and leave halfway through. Oh, no, that was not FreeWheel either. And you've been motivated to do that by something else, and it clearly wasn't a poor lecture. So what I want to talk to you today about is the microbes that are in and on and around all sorts of organisms, and are having much more subtle effects than some of the things we've discussed in the previous lectures in this series. So previously we've talked about microbes doing really subtle things like killing people. 

Speaker 1 (00:47):
Um, and, and tonight we're gonna talk about some of the much more subtle things that, uh, we think are influencing our behaviors on a sort of day-to-day basis. Um, and I've been talking about microbial manipulation for many years. Um, but, uh, nowadays I don't have to do any real introduction anymore because, uh, fortunately big time Hollywood has got in on the act recently. Uh, and some of you in this room, there are some people coming in. There are some seats at the front if you want. Grab a seat. Um, big time. Hollywood has, uh, come, come into this in the last few months, uh, with this series, the Last of Us, which some, if there's anyone seen that so far, some nodding yet in the room. Um, so maybe the people who are listening online are actually watching it in parallel, cuz they're, you know, it's more interesting. 

Speaker 1 (01:28):
Um, so this series, for those of you who are not familiar with it, is based on a computer game. Um, and it's, uh, a story about humans being taken over, uh, by an evil fungus that turns us all into zombies, um, happily, that itself is not, uh, based in facts. But the premise, the underlying premise certainly is because the idea for this, uh, whole genre of Gaines and uh, TV series, um, is a real life microbe that manipulates us. Um, and it's a, uh, in fact a group of species of fungus called cor deceptions, orio cor deceptions more recently. Um, and these are tropical fungi that live on insects. And the unique feature of these, uh, these kind of pathogenic fungi is that they manipulate their host to their own advantage. So these fungal spores are picked up by a variety of insects, depending on the species. 

Speaker 1 (02:18):
The one that you have in front of you is an ant specific fungus. The ant in its day-to-day process will pick up one of these spores and ingest the spore. The spore then hatches inside the ant, and it starts to grow inside the ant. And when it's exhausted, uh, everything it can get from the ant, it is about to spate and release its own spores. The fungus knows that it has a problem. Ants typically live on the ground or sometimes down in their burrows. If you spate inside a borough, that's not very effective way to spread. What you want to do is get a big airborne canopy. And so at that point, the fungus takes over control of the t's mind, and that ant, um, decides that it's time to go climbing, and it climbs and climbs and climbs the nearest available tree. And eventually at a certain point on, and you can see that here, and this ant latches on to a branch and then dies. 

Speaker 1 (03:03):
Um, and it dies now up high in the canopy that allows the fungus to now emerge from the ant. And you can see that here. That's this, uh, extended, uh, process coming out the ant and release spores. And because that ant is now several meters up instead of on the ground, those spores spread over a much wider area than they would've previously. So this is a microbe that has manipulated its host for its own advantage in a really quite acute and clever way, and quite a scary way. And this is of course, why Hollywood loves it, because yeah, the idea that this might happen in people too is nice and gruesome and very exciting. I have to say. Fortunately, we do not know anything like this in humans yet. And hopefully we never will, but you never know. 

Speaker 1 (03:44):
So this is quite a famous, um, and elaborate sort of manipulation, but actually a lot of microbial manipulation is much, much more simple than that. Um, and, uh, when a start, I'm afraid, as I very often do here, uh, with a, a tale of toilets, um, because a much microbial manipulation involves things around toilets. So if this, uh, that you can see in this picture here is shs is a foodborne bacterial pathogen. A caused a very acute and quite severe food poisoning. And in fact, this is a sample of, uh, what we refer to as delightfully as bloody stool, i e bloody diarrhea, uh, from a patient. Then you can see these little rod shapes in there, which are the bacteria shed by this patient. If you pick up cha, which you do from contaminated food and eat it, it very rapidly sets up an infection in the intestine. 

Speaker 1 (04:30):
Uh, and you soon know about it because what happens is you get very, uh, potent, rapid and uncontrollable diarrhea. Um, and of course the reason for this is because the bacteria is releasing a toxin chitin, um, that is highly pathogenic to humans and triggers a shedding of your intestinal lining. So you start releasing, uh, a lot of fluid and blood. Um, you get very rack diarrhea. The reason the bacteria is doing this is because if you can't control your bodily functions, you start to defecate all over the place. Um, and of course these days, hopefully in, in the western world at least you can make it to a toilet. But over much of human history and indeed still over much of the world, you won't make it to the toilet in time. And so the consequence of this, um, is this, you end up with contaminated, uh, environments with human feces, which contain of course, this bacteria. 

Speaker 1 (05:18):
And it's relatively straightforward to see, um, that once you have contaminated environments with bacterial feces, um, it doesn't take a huge leap of faith to imagine that you can rapidly then contaminate food and restart the cycle. This is a really unsettle sort of behavioral manipulation, but it works very effectively, right? If you are a Chael, you've gotta get from one human to another. A really good way of doing that is getting a human to poop all over their next set of food, um, and spread that disease very rapidly. This is one of the reasons why this disease spreads, particularly in areas like refugee camps where you may have poor sanitation, um, a very effective if slightly gruesome way of behavioral manipulation that spreads the disease. It's to the bacteria's advantage. And I think that's a really important thing to remember, is that the reason that a lot of pathogens do things like create toxins is not just to make our lives miserable. Um, they are in there because they have an advantage for the pathogen itself. So it's probably not that surprising that behavioral manipulation is also usually in the microbes advantage. And there are some really spectacularly exciting examples of that that we'll talk about later. 

Speaker 1 (06:26):
One, though, that many of us have experienced over just the last couple of years, in fact is much more subtle than that. Um, and is this kind of behavioral manipulation if you pick up a respiratory virus, um, most recently, of course covid 19. But the same is true for lots and lots of respiratory viruses, common colds, uh, influenza, a rhinovirus, whatever the symptoms you most typically get very early on are either coughing or sneezing. Okay? In both of those cases, these behaviors are incredibly advantageous to the pathogen. So this is a, an image obviously of someone sneezing. Typical human sneeze, uh, consists of about 40,000 droplets. Okay? Um, very interesting. Some of which go about nine meters, which is approximately from me to the back row here. So if I sneeze in a minute, bad luck, all of you. Um, so this is a big projection of material, 40,000 droplets. 

Speaker 1 (07:14):
Each droplet in a heavily infected individual can have tens or sometimes even hundreds of viral particles. And in fact, this has been measured recently for, uh, SARS cough two. And typically, although there's a huge variation between people, typically, uh, a single cough from a covid 19 infected individual has about a hundred thousand live covid 19 particles in it. Um, so it's not a surprise that coughing and sneezing is a very, very effective way of spreading diseases around. Hence, uh, the, the long-standing p back coughs and sneezes spread diseases, they really do. If you are a respiratory virus that doesn't trigger coughing or doesn't trigger sneezing, you are not going to do very well, and you'll be very rapidly outcompeted by one that does. So this is a subtle behavioral manipulation in the virus's interests, um, that happens every day, right? We all experience this. 

Speaker 1 (08:08):
So those are fairly straightforward. It's not a huge leap of faith to realize that to spread yourself causing people to have diarrhea or sneezing or coughing is quite straightforwards. But, um, to me the, the more interesting examples are the ones that get much more complicated and elaborate. And one of the most interesting areas for that is, uh, studying these pathogens that have multiple hosts. Okay? There are lots and lots of pathogens and parasites that require multiple hosts. One that we all think about if you travel in the tropics is malaria, for example, you know that malaria and many other pathogens are spread by mosquito bites, um, because they have two hosts. They have a mosquito host and a warm-blooded mammalian host, and they've got to move between the two. And it's in this group of organisms where they're having to manipulate two or more, sometimes separate hosts that we start to see the most interesting behavioral manipulations. 

Speaker 1 (08:57):
Um, and actually it's one of the areas where we have learned the most about behavioral manipulation is by studying those kind of organisms. So let me introduce you to a few. Um, this is, uh, many of 'em have terrible names. I'm so sorry for that. Uh, there's no exam at the end of this lecture. You'll be pleased to know, uh, so you don't have to remember them. Uh, let me introduce you. This one. This is Plagio Rinus trips off the tongue. Um, here it's an account fo kelan, uh, which is called a spiny. So there's a group called the spiny headed worms, uh, which is not very accurate cause they're not actually worms, but nonetheless, they do have spiny heads, as you can see on this one here. And this is a fascinating group because they all pretty much, uh, are parasites and they all have two separate and really quite unrelated hosts. 

Speaker 1 (09:40):
In the case of this one, uh, it lives most of its life in a woodlouse, okay? Um, but it cannot complete its sexual cycle in a woodlouse. It needs to get from a woodlouse into a bird. Um, in Europe, most of those birds are definitely starlings. Um, and it's gotta complete this cycle. And so, um, we have known now for many years that one of the most interesting things is if you go to an area where this para parasite is abundant starlings, and then you look at what starlings are eating, starlings are about 10 times more likely to eat an infected woodlouse than an uninfected woodlouse. And the reason for that is because when these guys get into a woodlouse, uh, they convince the wood lifes that it's time to get a, we kind of turn into a party animal, um, and start wandering around in the middle of the day, not hiding under leaves, going around in broad daylight and essentially making itself very visible, uh, for the bird to eat. 

Speaker 1 (10:30):
This is a parasite manipulation of the woodlouse that facilitates the parasites transmission to the bird and then completes the cycle. And actually, this group of acan LANs are kind of masters at this. There are species that infect, uh, shrimp in water and they convince the shrimp they should hang around at the surface, the water and cling to leaves looking very appetizing to passing fish because they need to go into the fish to complete their life cycle and so on and so on as a group of many, many species, all of which have done something similar, but in different sets of hosts. And that, I think actually is an interesting piece of biology because you would at face value think that manipulating a shrimp and manipulating a woodhouse might be quite tricky to do. And yet what this tells us is that evolution has managed to devise both of those systems and many, many others in a relatively short period of time. Uh, which probably goes to explain that, you know, we're all basically at heart pretty much the same. And so a lot of these manipulations are very similar in different hosts, which is a theme we'll come back to in a minute. 

Speaker 1 (11:31):
So the account for kelan are, are a neat example. Um, there's a much neater one, which I wanted to share with you. This is one of my personal favorites. Again, a really, um, trippy easy, uh, title. This is the Parasite Luco Clerid Paradox. I am no classic scholar as those of you who've been to these hecs, uh, before. No, but, but I think I can derive this from its Latin and Greek origins. So, uh, luco is sort of white, uh, chlor is kind of green, so it's a whitish greenish thing. And paradox means we don't really understand it. So it's a whitish greenish thing that we don't really understand, which is a very accurate description of this particular parasite. So this guy, um, is a fluke, uh, not as in good luck, A fluke is the type of type of organism aade. Um, and it lives in two hosts, snails of the gen snia, um, and then it has what's called a determinate host in a bird, we often talk in parasites that have two different sorts of hosts about intermediate hosts and determinate hosts. 

Speaker 1 (12:27):
And what that essentially means, intermediate hosts are the ones in which they do lots and lots of replication determine it. Hosts are the ones in which they, uh, complete their sexual cycle. So you need both of these hosts to complete your life cycle if you're one of these parasites. So this guy lives inside, uh, SIA snails. This is a normal snail. This is an infected snail. I think if you don't have to be a well-trained biologist to spot the difference between these two, uh, it's fairly obvious that this guy at the bottom has got some pretty technical ice stalks going on here. What has happened is the fluke has been ingested as an egg by the snail. It's hatched, and it has started to migrate. It's migrated its way to the ice stalks the snail, which are the things that do this in the end. 

Speaker 1 (13:10):
Uh, and it has very delicately eaten away the optic nerve. Um, so this snail is now blind, we can't see. Um, and that is very advantageous for the parasite because now the snail does not know if it's day or night or if it's on the top of the leaf or the bottom. And so these infected snails start to wander around in the middle of the day on top of a leaf for the parasite that wants to get itself into a bird. This is a very clever trick, not so great for the snail. Um, but it's really good for the parasite because now the snail is easy prey for the bird. But what I love about this parasite is it doesn't stop just there, it goes one step further. Um, and when it's sitting in that eye stalk of the snail trying to attract the, uh, bird, it does so with a bit of disco dancing that you can see here, pulsating up and down, um, sort of looking at all for all the world, like a little tiny caterpillar stuck on the head of a snail. And presumably, if you are a passing, I'd know blackbird, this is just like a super attractive snack. You eat the snail, unfortunately for the snail end of story, but for the parasite start of its new story as it moves into a new host, a very nice, neat bit of, uh, behavioral manipulation. 

Speaker 1 (14:20):
So, um, that's quite cute. Uh, and uh, you'll notice a common theme in all of these, uh, stories about, uh, things getting eaten. But, um, this one I think is one about, uh, which is, uh, the story gets even more elaborate. And here for this parasite, um, there is a, a nice twist in the tail. So this is Dickel dendri, another really easy. Now, I wish some come around and kinda just give these things common names. It would be much easier. Uh, it's another fluke. So it's relatively closely related, uh, to the ones you've just seen. This one though has a bigger problem because it has chosen for reasons best known to itself an evolution to have not two, but three separate hosts. It needs to complete its life cycle to start off in a snail, to move from that snail to an ant, and finally from the ant to a sheep or another grazing animal. 

Speaker 1 (15:10):
Um, and then eventually come out in the feces of this animal and, and restart the cycle. Um, so it has the same problem that those other parasites and pathogens have of trying to get itself from a host to a host, uh, but amplified because it has now three hosts to get through. Um, and so it has evolved some really clever trickery to do this. So if we start in the snail, the snail is, you know, crawling around and, and doing sort of snail things, it will pick up one of these as a cyst or an egg in the grass. It will hatch, it will start to replicate inside the body of the snail. And at a certain point it will irritate the snails lining sufficiently that the snail does the equivalent of I no gus, you know, snail diarrhea or snail sneezing or something, and ejects the parasite in a big ball of mucus. 

Speaker 1 (15:56):
Okay? Very successful. So now lying on the grass is a ball of mucus with the parasite within it. Um, this mucus is kind of sugary and sticky and is just the kind of thing that ants like. So a passing ant that sees this ball of sticky mucus, we'll pick it up and ingest it. Um, and now the parasite really goes to work because it enters the gut of the ant, it starts to replicate. Um, and then once it's done there quite repeatedly, that you can get up to several hundred parasites in a single ant, then what happens is one of those individuals, anyone starts to migrate up the T's body, uh, to the base of ganglion the ants brain. And once it gets there, it now tells the ant start doing some pretty crazy stuff. Uh, what happens at infected ant is it will go up the nearest blade of grass right to the top of the blade of grass, clamp its jaws on, and then do a little bit of a handstand at the top of the good blade of grass. 

Speaker 1 (16:49):
Um, why is it doing this? It's doing this because if you need to get from him to him, the best trick you can possibly do is sit at the top of a juicy young blade of grass, cuz then along comes your innocent unsuspecting sheep nibble, nibble, nibble, nibble gets ant alongside its grass, completes the lifecycle. That's pretty cute. But what is even cuter is if that ant is on top of a blade of grass and it gets a bit hot, um, the parasite is now in danger. If it gets so hot that the ant dies, the parasite dies with it. The parasite knows this. So if the air temperature rises to undesirable levels, it somehow releases its hold on the ant. And the ant then goes back down to the ground and starts wandering around. And, you know, presumably does the ant equivalent of kind of waking up after a late party and somebody else's house. 

Speaker 1 (17:33):
I'm wondering how you got there? Um, uh, and, and, and goes back to normal life. And then when the temperature calls down again, the parasite re exerts its effect and up goes the end and does it again. So you have like a remote control ant. And I think this is the first instance we've seen of a parasite that really has a very elaborate level of control over the host. Um, we don't know how it does that, but I think understanding this process could tell us quite a lot actually about this kind of subtle behavioral manipulations. So remote controlled ants, uh, sheet and snails, all pretty cutesy. Um, so we've heard a bit about, you know, things that get eaten, things that manipulate woodly, all of these kind of things. And, and you're probably sitting there thinking, why did I come to this lecture? I'm a human, uh, not happily an aunt or a sheep. 

Speaker 1 (18:16):
Um, surely none of this has anything to do with me because as we know, humans have free will. Um, and, uh, therefore a parasite manipulation is totally irrelevant. Just as a completely irrelevant aside, actually this, uh, film her own free will. Um, uh, it was a 19, I think 1985, something like that. Early a film was someone of the early sign of films and is lost. No one knows the plot of this because the film has been lost. So, uh, so we actually don't know whether she had free will or not, but let's assume she did. Okay. So, um, so we all have free will. We don't get manipulated by things we think, but of course, actually we know that's not really true. Um, because, uh, most of us grow up learning a little bit about infectious disease. And one of the ones we learn a bit about is this particularly unpleasant disease, rabies. 

Speaker 1 (18:59):
Okay? Happily, uh, not present in the United Kingdom, but still, of course, a problem across many parts of the world. And rabies, if you haven't come across it, is aics virus. It's a virus that replicates in the nervous system of animals, and it does that in order to manipulate, uh, its host quite dramatically. So typically this is a, a dog, uh, virus. Uh, and infected dogs, unfortunately, like these ones here, display these very clear symptoms, okay? Um, the virus is transmitted by bites and scratches in saliva typically. Uh, and so, uh, what it wants to do is maximize its transmission from host to host. Um, and so it causes, first of all, its infected host to salivate. It produces a lot of virally infected saliva. And secondly, it drives fear and aggression in its host so that that host is more likely to bite another host and spread the disease. 

Speaker 1 (19:50):
And this is of course one of the reasons that if you travel to countries where rabies is still present, um, your advice to stay well clear of any animals, particularly those showing abnormal behaviors. Um, so here we have a virus that's triggering a whole bunch of things that are in its own benefit. It's getting saliva going, it's triggering anxiety, paranoia, confusion in its host animal, um, and unprovoked aggression. If you are unfortunate enough to be bitten by a Arabia dog, you will go on to display exactly the same symptoms. Humans infected with this become confused. They start to hallucinate, they become aggressive sometimes, um, and they are essentially displaying the behaviors of the virus. And unfortunately, it's untreatable at that point. It's always fatal. Um, but ultimately this is a virus that is manipulating our behavior in a really quite unsettle sort of way, despite the fact we have known about rabies for hundreds of years. 

Speaker 1 (20:41):
And in fact, there's been a source of great, uh, research activity for the last probably 150 years. We still don't really know how this simple virus manipulates the mammalian nervous system in such an elaborate way, although recently we have seen, um, some very interesting findings. So, uh, what you see here on, on this side of the screen is a protein structure of one of the proteins on the viral surface, the glycoprotein. And it turns out that this part of this protein from the virus, um, binds to a Nico acid, uh, receptor, which is one of the, uh, uh, neurotransmitter receptors in the human, indeed the dog, uh, nervous system. And it seems to suppress it. Um, and that's has a consequence of lowering serotonin levels in infected individuals. And you might know that serotonin is often referred to as the kind of feel good neurotransmitter. 

Speaker 1 (21:31):
Um, people are told to do things like eat lots of bananas and chocolate, cuz it gets your serotonin up and it makes you happy. Um, and, and Lucy speaking that it's true. So low levels of serotonin are correlated with, uh, depression and anxiety and some of the behaviors that we see virally infected individuals. I suspect this is not the whole answer, but certainly there is some evidence here that the virus is actually quite, uh, targeted in terms of playing with individual components of the human nervous system to trigger these sort of, uh, weird and wonderful behaviors. 

Speaker 1 (22:02):
So rabies happily, uh, as a disease that we don't encounter firsthand very much these days and, and hopefully one day might even eradicate. Um, but behavioral manipulation is not limited in humans to these really dramatic, you know, let's all go and froth American bite people kind of behaviors. There are much more subtle behaviors. And the one about which there has been the most interesting recent, uh, decades, and perhaps is, is the tool with which you might unlock some of these mysteries. Um, is this guy here, toxoplasma Gandhi eye. So this is a parasite, you can see it in front on the screen in front of you. Um, that is sort of loosely related to, uh, things like malaria. Um, and this parasite, uh, you might have come across in fact, uh, particularly if you're female and have had kids. So this is something you should be tested for if you're pregnant, uh, or indeed preferably even before you get pregnant. 

Speaker 1 (22:50):
Um, it is not generally a problem for humans, although it's transmitted, um, quite readily through things that undercooked food. Um, but if you're immunocompromised or if you're a very young infant, this can cause quite a serious disease. Um, the big problem actually in humans is not to the person infected, but they're unborn infant if they're a pregnant female, because this is one of the few parasites that can transmit across the placenta. And if it does that, um, then the unborn infant can be very severely affected or indeed killed by this parasite. So we typically screen for toxoplasma antibodies in pregnant women to understand, uh, whether they're at risk of this or not. Most cases, by far and away most cases of this though, are asymptomatic. You don't know if you're infected with this parasite, um, because once it enters the body, it forms a latent cyst. 

Speaker 1 (23:37):
So it goes dormant, uh, typically in either muscle tissue or in nervous tissue. Um, it's not dead, but it's, it's silent. It's uh, it's kind of hiding out if you like. Um, and that we have known for a very, very long time. And if you read medical textbooks, uh, it will tell you this isn't asymptomatic infection of no consequence. But recent data suggests that's not actually entirely true. So why is that? So here is, it is quite an innocuous little thing actually is zipping across the screen there. Why, why am I saying this is not entirely true? Uh, the reason I'm saying that is because we have learned quite a lot about this parasite and its manipulation of hosts in its natural hosts. Humans are not the natural host for this organism. It's natural environment, um, is like many of the things we've been talking about tonight between two different sorts of hosts. 

Speaker 1 (24:24):
It lives most of its life in a rodent mouse or a rat typically. Um, but it needs to complete its life cycle in a feline. So in this country that's typically a domestic cat. Um, but of course out in the rest of the world it could be a lion or a tiger. Now it's relatively easy to see, you've learnt quite a bit, hopefully so far that it to, for the parasite to get from here to here is quite straightforward, um, in one sense because as we know, cats really like mice as you can see in this particular photo here. Sorry, I couldn't resist that. <laugh>. Um, uh, so, so cats quite like mice. Um, and so on the one hand, being a parasite that infects mice and needs to go to a cat is quite clever, uh, cuz at least one of your hosts is looking for the other one already. 

Speaker 1 (25:04):
The problem is that the other, the reverse is not true. Rodents don't generally like cats and there's a very good reason for that. Um, and so if you're a parasite, and they're quite good at evading cats, right? So if you're a parasite, um, it's not really great that your first taste here doesn't get anywhere near the second taste. And so the parasite has solved that problem because in infected rodents lose their fear of cats. And in fact, heavily infected rodents start to seek out cats. They, they're attracted to cat urine, they hang around the cat literary, and they do all sorts of very unwise things. If you're a small rodent, um, they have become resistant to fear this particular sort of fear in particular. Um, they are no longer scared of going around open spaces. And in fact, you can see that here's, here's a little video. 

Speaker 1 (25:47):
Um, you can see at the top of a wild, a normal mouse, you can just about see the mouse. Hopefully he's in a, a big white box here. He doesn't like being in the big white box quite sensibly. Uh, and he's hiding at the corners, okay? He's looking for a way out. He's doing a kind of mouse sort of thing. Those of you who've encountered mice in your, in your homes or wherever, you know, they, they're running along the corners. They hide in the skating pool. They don't sit in the middle of the room waiting for you. But a toxoplasma infected mouse doesn't behave like that at all. Look at this one down here. He's zipping all over the place. He's really happy, quite brave, happy to go out and about, um, uh, into the environment. Um, great for him. Not so sensible if there's a cat around. 

Speaker 1 (26:21):
Uh, and so these toxoplasma infected rodents are significantly more likely to be eaten by passing cats completing the cycle. That's bad news if you're a mouse and kind of not so great news if you're a cat either. Um, what's it got to do with people? Well, it turns out, so in people, uh, this parasite doesn't want to be an us at all. We're a dead end host. Uh, but it gets into us quite a lot. Um, and in fact, you can find this through all sorts of processes. So this is an MRI scan of someone admitted to hospital for another purpose actually. Um, and in that MRI scan you can see here, um, a small white blob that is a toxoplasma cyst in the brain of this individual, probably asymptomatic, I dunno why this person was admitted car crash or a fall from a hide or whatever. 

Speaker 1 (27:03):
Um, but the, the, the CST was discovered there. And actually some of you might have had this experience when you are, um, I dunno, having an MRI for something else or, or sometimes a muscle biopsy and they might come back and say, oh, you had a toxoplasma, um, and you think, gosh, you know, was that bad? And they're like, no, no, no, no, don't ignore it. Um, however, so they get into the human bodies, were a dead end host. Um, but uh, and for most of the time that we've known about this, we have assumed that was without any consequence. But it turns out not to be entirely true. So if you are latently asymptomatically infected with this parasite, you're actually still significantly more likely to suffer from a variety of mental health issues. Schizophrenia in particular is significantly more common in people who are harboring Tola. 

Speaker 1 (27:45):
Uh, and slightly more. Um, bizarrely it turns out that the incidence of tox, plasma infection is about twofold, higher in people who crash their cars, particularly if you've crashed your car, um, in a way that was basically related to you driving like a lunatic. Um, so if you run a red light, if you drive too fast, if you those kind of things that crash your car, um, you're much more likely to have a tux spasm. Why is that? We think that is because the parasite, although it cannot complete its life cycle in a human, um, is essentially treating us like a rat. Um, cause as we know, humans are basically rats with less hair. Um, so it's treating us like a rat and it is trying to do all of those things that it does in a rat or mass. It's trying to make you a bit brave, go out and about, not be afraid of stuff, um, and do unwise things like run red lights in your car. 

Speaker 1 (28:30):
And so your behavior is being manipulated by this parasite cuz the parasite foolishly thinks that might help it end up in a, in a, maybe it will help it end up in a cat, but, uh, you know, probably not, perhaps. So this is, these are kind of pathological things. Crashing your car is not great. Having schizophrenia is certainly not great. Um, but one of the most interesting kind of facets of that has been much more recent data suggesting that this parasite might also be doing things that we think of as very, very human behaviors. So if you open your own business, you are significantly more likely to be tolas infected than someone who doesn't open their own business. And the logic behind this is cuz opening your own business is risky, right? You might, you know, it might not work. Um, and, and so the parasite maybe is helping you to take that risk when if you're not parasite infected, maybe you don't. 

Speaker 1 (29:17):
Um, the unfortunate consequence is it might help you start your business. It's also more likely to help you go bankrupt cuz you are also more likely to go bankrupt if you have, uh, toxoplasma cysts in your body. All of this is quite cute and gets even cuter when you realize that, um, in the UK for example, about 30% of people are latently infected with toxoplasma. Um, so, you know, for those of you in the audience here in the room, you look left and right and then decide which of the three of you is carrying the parasite <laugh>. Um, you, you may wish to decide between you who's driving home tonight based on that. Um, but the idea that fundamental human behaviors like risk aversiveness might actually be being influenced by hidden parasites, I think is a very, very neat and slightly disturbing idea. So toxoplasma is one of the, uh, the kind of things that we know the most about. 

Speaker 1 (30:06):
We still don't know how it does this. What are the molecules it's using, what are the signals it's using to manipulate it? What are the consequences for the human immune, uh, nervous system? Um, but we know quite a bit about it. But what I want to turn to now then is the stuff that we don't really know much about, but might, I think if I had to guess next 50 years, what's gonna be the big story? Uh, and the big story I think is gonna be what are we missing currently? What might be out there that is doing all sorts of interesting stuff, um, that we have never thought about. Um, and those of you who have come to any of these lectures previously, uh, will have heard me rabbit on at length about the microbiome, okay? The fact that we are living walking zoos full of interesting microbes. 

Speaker 1 (30:48):
Um, this is an image, uh, from a group of us demonstrated where they looked at different body sites and, and quantified the different diversity of microbes living on. Though you don't need the details, the point is we have microbes everywhere. The soles of your feet up your nose, under your armpits or whatever, the balance of them is wildly different. You know, the, the type of micro cribs living between your toes are different to the ones living between your fingers. Um, most of them, many of them we know nothing at all about beyond the fact that they are there. Um, and we dunno what they live on, what they produce, what they do. Um, and the big black, uh, box, if you like, the one that we've talked about, uh, multiple times in this series previously is the stuff that lives inside you. And for those of you who missed a lectures, um, your gut microbiome, the, the range of organisms inside your gut is extraordinary. 

Speaker 1 (31:34):
Numbers vary wildly, but whichever way you cut it, we undoubtedly have more bacterial cells in our intesine than we do human cells in our entire body. So to a first approximation, you are definitely not human. You're probably microbial. Um, and, and that's just the bacteria, right? There are fungi, there are viruses, there are parasites, there are all sorts of interesting things stably living in your microbiome. Point one 0.2 is it changes crazily. You eat a sandwich on your way to this lecture, you've changed your microbiome, you go to the toilet at the end of the lecture, you've changed it again. Um, when you are born, you, you acquire a microbiome from your mother, it then evolves over your infancy. All sorts of things happen to the microbiome. And we are already familiar, hopefully with the concept in the kind of popular press that the gut microbiome might be really important for things like guts health, um, for, you know, if you have, uh, I dunno, ulcerative colitis or some of these conditions, gut microbiomes really important. 

Speaker 1 (32:29):
What might be about the Lord break though? And if I had to gamble, I would say this Syd is the role that it may be having on our minds or so, um, why do I say that? Why might the things in your gut have an impact on your mind? Well, first of all, the first reason for saying that, um, is really good experimental data from other models and particularly, um, from mouse models. So, uh, let me introduce here. This is a mouse. You can just about see the mouse here. And this is a typical behavior of mouse mice. We've heard about mice a lot this evening, and I'm gonna hear some more. Our mice are scared, right? Mice don'ts typically come out and about, they're not very sociable creatures, at least with humans. If you raise a mouse so-called germ free in a sterile condition. 

Speaker 1 (33:09):
So the mouse has no microbiome at all. This significantly more kind of nervous. It has different traits. It's described all of this, it's described by animal technicians in slightly aloof in its interactions with other mice <laugh>. Um, when it has no microbes, if you then transplant in microbes from a normal wild type mouse, it starts to become a little bit more confident. If you change that, uh, that kind of, uh, ingredient list, the types of microbes you, uh, transplant and in particular one called lactobacillus, if you have more lactobacillus, the mass becomes even more confident and starts to be much more outgoing. Um, probably not wise if you're a mouse actually in some senses. Uh, but you can manipulate a kind of pretty obvious behavior around how an anxious that mass is by the contents, uh, of it microbiome most interestingly, I think is recent data, uh, in another road. 

Speaker 1 (34:00):
And this is a rat obviously. Um, and in rats, uh, there's been a lot of work done on, uh, mental health. If you like, mental health of rats, um, mental health of humans modeling rats. Uh, you can induce a state, uh, that is like depression in a rat by stressing it out effectively. If you stress out a rat enough to create a type of depression, not all rats will do this. So you have a, you know, a bunch of rats, some rats in response to that stress will develop, uh, behaviors that look at it a bit like depression in humans. They become lethargic, they go off their food. They don't want to do, uh, go out and about. Not all rats do that. If you then take the microbiome so that a sample of bacteria from the depressed rat and transfer it into a rat that has not had any prior experience, that rat on its own does not become depressed, but it then will become very rapidly depressed with a relatively low stress burden, much lower than the first instance. 

Speaker 1 (34:51):
And converse the other way around. If you transfer a healthy microbiome to a wrap that's looking depressed, it will buck up. Okay? So here there is a kind of a real world example of something as subtle as kind of depressive mood being quite strongly influenced by the microbiome. The most interesting thing though about that I think is it on its own, it's not enough. So you can't just transfer the microbes and while you've triggered depression or you've cured depression, and I I suspect the same will be absolutely true of humans. It's about the context that happens. So you need that transferred microbiome and also that secondary trigger of a, you know, animal technician stressing you out or whatever to trigger the full effect. But nonetheless, the microbiome is predisposing you one way or another to respond. So how might that actually happen? What might actually be going on? 

Speaker 1 (35:43):
Studying this in rats, mice, or let alone humans is really tricky cuz we have very, very complex microbiomes, um, with thousands of species, billions of cells, really tricky. So people have started recently to turn to much simpler models, um, and one that, uh, just very recently has shown some really, really interesting results, I think is one of my favorite laboratory models. This is the nematode worm cite elegance. You gonna swim across the screen in front of you. It's a microscopic, um, nematode worm about, uh, just under a thousand cells in the bodies. It's a very simple, uh, model, uh, but a really powerful model for understanding lots of things. Nematode worms eat bacteria all the time. Um, and so they have a gut microbiome just like we do with bacteria. That's a mixture of the stuff they're eating and digesting and stuff that is, uh, permanently present there. 

Speaker 1 (36:32):
Um, and uh, what has recently turned out is that one of the organisms they can come across is a bacteria called Providencia. Okay? And Providencia will, uh, occupy the intestine of the worm and live there just like our normal gut, uh, microbiome whilst it's living there. It turns out that that bacteria is producing a molecule called tyramine. Um, and tyramine is converted by the worm into another molecule called O topamine, which is a neurotransmitter. So this bacteria is essentially providing a source of neurotransmitters of the worm. And what turns out to be quite cute is that neurotransmitter crosses the border into the worm and starts to alter the behavior of its neurons. And the very, very clever thing about this is that by doing that, that neuro signal encourages the worm to go and eat more providential. Uh, and so it's seeking itself out through this manipulation. 

Speaker 1 (37:22):
And this is one of the first examples we have of a real molecular handle. There's a single bacteria producing a single neurotransmitter and triggering really quite an elaborate, uh, behavioral choice in the worm, what bacteria's gonna eat next. Um, this is a worm. We don't have oc topamine signaling, so this is probably not happening in us. You'd be pleased to know. Uh, but what has turned out to be quite interesting is that although we don't have OC topamine, we have an awful lot of bacteria in the gut that produce this molecule. This is gamma aminobutyric acid or gamba. Um, it's a very, very widespread neurotransmitter in the human immune system. And broadly speaking, it's a kind of shut down neurotransmitter. It silences the behavior of neurons. And it turns out that this molecule is made by an awful lot of gut microbiome. Uh, uh, inhabitants is also broken down by quite a lot of bacterial species. 

Speaker 1 (38:14):
So the amount of GABA that's in your intestine at any one time can be wildly fluctuating depending on whether you've got more makers or more breakers of this molecule. We know it can cross the intestinal membrane. And so I, and although we haven't demonstrated this, I think it's really quite plausible that the level of this neurotransmitter in your gut will be affecting the neuro signals in the rest of your body, um, including perhaps influencing things like mood appetite and other behaviors. Um, we're a long way off really knowing how that actually works. Uh, but I think it's a really nice example of a potential molecular mechanism that gets us from, uh, you know, theoretical correlations between the microbiome and actual behavioral interventions. So all of this is theoretically possible it might be influencing X, Y and Z. Is there any real evidence, uh, beyond those Morrison rat studies that it really is doing something? 

Speaker 1 (39:06):
Um, and I think the short answer that is yes, it's starting to come. Uh, so, uh, there's a really interesting study quite recently done by, uh, colleagues at Oxford and other universities where they have taken a lot of people, this is not the, these, these are not the people they took, uh, but a lot of people, um, and they have analyzed the microbiome of those individuals, so the diversity of bacteria and fungi in their guts. Um, and those people have also filled in questionnaires that are designed to probe their characters for all sorts of interesting traits that psychologists measure us on. Um, like for example, how outgoing are you? How reserved are you? How likely are you to make new friends? How fearful are you of that kind of your cocktail party scenario? So on and so forth. And it turns out that there is a really interesting link with the microbiome, which you can see on this graph here. 

Speaker 1 (39:50):
So for example, if you score higher on sociability, you are the kind of person who likes to go out and meet new people and, you know, have a cocktail party or whatever. You have significantly more of this kind of bacteria amania than someone who's much less sociable. Okay? Conversely, if you have what people call neurotic tendencies and the psychologist uses to kind of catchphrase for, uh, you know, you're a bit fearful, you tend to think of other people are out to get you or, or whatever. Um, if you have more neurotic tendencies, you have significantly less carum than someone who's not so neurotic. Now, the, the, the big caveat here, of course is that we don't know cause and effect. Maybe being much more sociable means you go and eat different stuff with different people and you pick up more amania that's possible. Um, but I think together there's quite a strong suggestion here that the relative balance of different bacteria in your intestines may be influencing things as subtle and as apparently human as our propensity to go and socialize. 

Speaker 1 (40:48):
Um, and, and as we get more and more data on this, which is happening very rapidly now, uh, I think we'll see more insights in here. And, and you might be aware this fact, some of you might have done this, you can now have your gut microbiome commercially sequenced if you so wish you can send off a poo sample and a company, uh, you know, for a small amount of money will come back and tell you what you've got. And my slight caution there is of course they might tell you what you got on, you know, 6:00 PM on Tuesday by 9:00 AM on Thursday, it might be wildly different. So, you know, don't take too much stead by it. Um, but the, that huge amount of data that is pouring in from people's gut microbiome, large scale studies of behavior and genetic studies of the host, I think will lead us within a relatively short time to start to make interesting predictions around things. 

Speaker 1 (41:30):
And who knows, maybe even intervene. And I think, you know, uh, the prospect of intervening to make someone more sociable is quite terrifying. But the prospect of intervening, uh, to, you know, to deal with things like depression, um, uh, I think could, could be, you know, a real game changer for medicine. Um, so these are some of the various behavioral interventions that my Crips do. There are lots more to discover, I think. But I want to end, uh, just with a slightly upbeat message. It's slightly depressing, I think at this stage. Think, well, you know, uh, maybe nothing I do is really me. It's all about microbes instead. Um, and, and just to reassure you, I don't think that's really true. Uh, so let me end with this rather than I, I'm quite a big fan of Turner paintings. This is a, a great turner painting. 

Speaker 1 (42:06):
Um, this is, uh, hero and leander, and if anyone knows you're Greek mythology. So hero, only li leaner, um, they were lovers. They were separated by a sea. Uh, and every night a hero would wave her lantern down here and Leander would swim across the sea, uh, to see her, and then he would swim back again. And then one night, uh, in this, uh, myth, the the candle blew out, um, leaner got lost the sea and he was drowned. Um, and uh, when he, when his body was discovered, uh, hero jumped in and killed herself too. Uh, so this is a great romantic tragedy. Why am I showing you this here? I'm showing you this to reassure you that I don't think great romantic myth tr are, are, are written as a result of bacterial intervention. I don't think that Turner's genius to, you know, to create this was driven cuz he had a parasite in the brain. But it might be worth thinking about the fact maybe Turner's flamboyant genius was a little bit influenced by his microbiome and maybe whether we like paintings like this or we like stories like that or not, might not solely be down to your personal feelings, but also due to whatever you ate that morning and influence your gut microbiome. Let me leave it there and take any questions. Thank you very much, 

Speaker 2 (43:18):
Professor may, thank you very much. Thank you. We've got time for a couple of questions. So let me start off with the room. Uh, my colleagues got a roving mic, so if you put your hands up for me, if you've got a question. 

Speaker 3 (43:30):
Um, I wanted to, so a lot of your specific manipulation examples involved behaviors that the microbes are doing that they had sort of particularly got landed on that were suited to their life cycles. Um, I wa I was wondering in the human situation with the mass complex of organisms is, are they all also there for a particularly adapted reason or is there some moment of randomness in terms of what neurotransmitter they happen to secrete that happens to fit closely into one of our receptors? Or, and not to mention also is there any like, coordination among the sy on a system level of the microbes in, in the organism? 

Speaker 1 (44:06):
Thanks, I mean, yeah, those are really great questions. So first thing to say that I think you're absolutely right that the, the, the almost the simple, um, uh, scenario of a parasite in its host, uh, is the kind of the, the ultimate part of simplistic behavioral manipulation, right? If you need to get from A to B, anything that helps you get from A to B faster is good. Um, and so those very straightforward manipulations, like let's get my host eaten, are much more common in pathogens in commen. So organisms that live with us like the gut microbiome, it's much less clear whether there is an advantage in terms of that host manipulation. And I suspect the short answer might be not in many cases. Um, many of these neuro, so the gamba I mentioned this, this neurore that's produced by bacteria, there's no evidence they're doing that because it works on humans. 

Speaker 1 (44:51):
Um, but this is a widespread molecule that is a benefit to the, to the bacteria itself. Of course there is a slight follow through though that you might produce this for a completely different reason if you're bacteria. But if it then triggers a behavior that is going to, to help you spread that evolution will, will select for that behavior. Um, and say if you wanna really push the boat out and that, that's the fun thing about Gresham lectures, right? I can speculate wildly now, you know, imagine a bacteria producing a neurotransmitter that makes someone more sociable, therefore you host more parties, you cook more food, you spread that bacteria more successfully to the people you're entertaining, the bacteria's done very well. And so actually there is a selective, an indirect selective pressure for that very subtle level of manipulation. I don't think there's any evidence that that's what's happening now, but it's at least a theoretical possibility that some of the things we do, um, start to come in. Interesting. And of course, you know, you can go wild there and think about partner choices and sexual behavior and all sorts of things that we do that spread microbes around. So, um, who knows you're look in the mirror later and think, am I doing this because it's me or not 

Speaker 4 (45:53):
<laugh>, I had heard of maybe this is wrong, that there are some gut gut bacteria that are bad for people, you know, that make it difficult to digest and make you fat, whatever. I mean, wouldn't that be kind of counterproductive for the bacteria? 

Speaker 1 (46:07):
Yeah, that's a very good question. So, um, so aren't there, so there are, there are, there are, there are two there Were definitely gut bacteria that are bad for you. So you think about, um, uh, well say for examples that I mentioned cholera, you know, lots of things that are really, really bad for you. Um, I think what you are, you are, you are getting at more is the more kind of the commensals. There are, there are patterns of microbiomes that are associated with disease and in fact quite good evidence that things like irritable bowel syndrome, uh, people have a different sort of microbiome and indeed in some cases changing their microbiome will help deal with their symptoms. Um, so the question is, is that good or bad for the bacteria? It's not necessarily bad because of course some of the things that are bad for us as humans are quite good for the bacteria like diarrhea, like, you know, poor dietary control, those kind of things might be advantageous to the bacteria. 

Speaker 1 (46:52):
Um, and it's all about the relative balance. So if this is something that bacteria does that is beneficial to the bacteria and happens to be bad for you, it will probably still be selected for, um, the interesting question becomes whether there's a behavioral manipulation that is bad for us, but good for the pathogen. Uh, and I think that is potentially possible of course if it's so bad for us that we die in the bacteria die with us, it's going to get eliminated by evolution. Uh, but it's certainly true. That's a rather long-winded answer. It's certainly true that there are microbiome patterns quite strongly associated with disease. Um, none of those that I'm aware of yet are specifically linked to a particular behavior, but it's theoretical possible they could be. Definitely. 

Speaker 2 (47:29):
Um, I've just got one from the online audience for you. Is there a treatment for toxoplasma? You may have mentioned it, but 

Speaker 1 (47:36):
Yeah, is there a treatment for toxoplasma? So there is, so there there are two different questions there. So, um, acute toxoplasmosis, so when the parasites are really growing and causing disease people, uh, there are treatments, it's a bit tricky. Um, but there are treatments for that, um, the asymptomatic. So if you haven't, uh, you know, a latent cyst, I mean theoretically you could probably do things to that patient to remove that asymptomatic cyst. Um, those things that you would do are actually not in themselves. Very good. Uh, so I don't think there's any reason at the moment that if you, you know, for those of you out there thinking I'm one of those 30%, don't panic, I would not recommend trying to get rid of you asymptomatic cyst. Um, because it's, I mean it's fine. I should have made that clear. It's very, you know, unlikely just because you have a cyst, you will become schizophrenic for example, but you are slightly more likely to be schizophrenic. Um, so there's no kind of medical justification of the treatment. They do exist, but, but the minute, the risks, we massively outweigh the, the benefits when it comes to other pathogens. I mean, the idea of tweaking your microbiome for benefit starts to become more interesting. But, you know, it's in its infancy that I think at the moment, 

Speaker 5 (48:35):
Um, red of, um, outbreaks of, um, mass, um, hysteria course by fungi. Um, do you think that that is a form of mutation or it's just an accidental symptom? 

Speaker 1 (48:48):
Right, so, well, so, so at the moment, mass, mass behaviors caused byf fungal evictions are, are still stuff of science fiction happily. Um, there, there is though an interesting question about mass behavior and we know that right for hu lots of human behaviors, you can think about things like kind of cult behavior that we sometimes come across where people do all sorts of bizarre things, sometimes even mass suicide. Right? Um, how much is that likely to be to do with a microbiome? Uh, I mean, I suspect the answer is very, very little. But, uh, I wouldn't rule out the fact that we might, I don't, I really don't think there's a parasite out there that's gonna spread through this room and we're all suddenly gonna go and, you know, do something bonkers later. Um, but the idea for instance, that you might have a particular sort of microbiome that predisposes you to think the world is out to get you or the world's about to end, or there's a, I dunno, it's flat or whatever, any of these other conspiracy theories is not beyond the realms of possibility. 

Speaker 1 (49:38):
I don't think there's a parasite that makes you think the world is flat, but there might be a parasite that makes you more skeptical of kind of scientific evidence and therefore you're more likely to think about the world being flat and you've clubbed together with other people like that and you self aggregate. Um, it would be a very interesting study, uh, to do the sort of microbiome of people who belong to kind of crazy cults. I suspect we might struggle to get, you know, people to register for that <laugh>. Uh, but you know, if anyone out there isn't a crazy cult and wants to volunteer, let me know afterwards. Um, 

Speaker 6 (50:03):
Uh, there's a, there's a difference between, uh, in your microbes, what viruses and bacteria. Now the viruses like influenza for instance, uh, when it strikes body and the person and the person succumbs and dies is at the end of the virus. And in the case of bacteria, cause it'll continue living. What happens to it if, 

Speaker 1 (50:29):
Yeah, so, so you raise a very good point there. Um, the, so there the key is the transmission route of the organism. So, um, influenza is a good example. Influenza requires a human cell to replicate. If you die, you know, it'll be viable for a few hours, but eventually it will go. Um, there are of course viruses that are very successful at spreading from dead bodies. Ebola is a very good, you know, case in in point where it triggers this bleeding, it's blood transmitted. Um, and actually a lot of Ebola transmission is, uh, during funeral rights where people are, are touching the dead body and, and picking up tissues. So it's not a given that the end of the host is the end of the organism. Um, and for some bacteria, as you mentioned, in particular, uh, they can be very, uh, very separated. So anthrax, uh, can live for 50 years without a host in the soil, no problem. 

Speaker 1 (51:13):
Um, so death is not necessarily a problem and actually it could be an advantage. It's quite an interesting sort of bit of speculation around some organisms that might feed off the decaying body. So I work on a, on a fungus called crypto cocus, um, that is good at uh, uh, eating decaying bodies. And so there's some idea that maybe actually killing host is not a bad thing cuz it gives itself a nice little nutrient store for the next, you know, six months to kind of live off. Um, so they're not, they're not specifically linked. Um, but you are, you are right that generally most pathogens don't want to kill a host, certainly up fast because by killing a host fast you reduce your, your ability to propagate. Uh, but there are good reasons why you might still need to kill your host to facilitate transmission, uh, for example from blood or, or other bodily fluids. 

Speaker 7 (51:55):
Um, do you think that we could genetically manipulate microbes? They use neurotransmitter to manipulate as such in a good way, such as ulu fear just as Toxoplasma go mouse. 

Speaker 1 (52:06):
Sorry, I missed that the second bit. Yeah, so, so do I think there's neurotransmitters 

Speaker 7 (52:10):
Yes. The neurotransmitters that they, uh, pass to the mouse 

Speaker 1 (52:14):
Oh, for toxic transplant? So do I think it's making neurotransmitter That is certainly possible. Um, and I mean as in the bacterial example, a lot of people often think, oh, neurotransmitter must be a really, really complicated molecule. Actually a lot of neurotransmitters are quite simple molecules. Uh, so it is certainly reasonable, I think that toxoplasma and other parasites might be making those kind of human active neurotransmitters, uh, as far as I'm aware. So toxoplasma is very intensely studied, so I guess a little bit of me thinks that if it was that easy, we might have discovered it by now. Um, but of course the nervous system's incredibly complicated. Um, so it's quite possible it's making something that is not itself a neurotransmitter, but is maybe processed into one or inhibits one that's already there or something. Um, there are lots of subtle ways to manipulate it. Definitely possible and certainly for other microbes. I think it's now very good evidence that many, many bacteria make human active neurotransmitters. And that's probably a big part of this, um, this dynamic. 

Speaker 8 (53:09):
Thank you. Uh, these microbiomes that cause behavioral changes, are they, uh, due to an e some dark evolutionary, um, development or purely accidental? 

Speaker 1 (53:26):
Um, so yeah, a dark evolution is quite scary concept, isn't it? Yeah, so, so I mean essentially all evolution is accidental, right? Stuff happens, we mutate something and, and then essentially evolution works by selecting the things that are advantageous and killing off the things that are disadvantageous. Um, so I, so I definitely don't think that all these manipulations have arisen as some kind of orchestrated plan or some kind of, you know, evil power that's trying to take us over. Um, what has happened, so in the case of toxoplasma is perhaps the simplest, you can imagine that the ancestral toxoplasma did not manipulate rodents. Um, something happened, some mutation happened and it happened to produce perhaps a neurotransmitter and that therefore that parasite's mouse was more likely to get eaten. Now there's a massive advantage that parasite is selected, it does much, much better. The other lineages go extinct. 

Speaker 1 (54:12):
And that is now the one that it's worked on. And I suspect something very similar for the microbiome as a whole, where you've got these things that might be very subtle, but of course on a, on a scale, you know, even if you, if you increase your likelihood of transmission by 0.001%, but you do it in 6 billion humans, you very rapidly have a major natural selective advantage. So, so yeah, I don't think it's a, a sort of dark orchestrated plan, but I do absolutely think that, you know, natural selection is selecting these things for their, for their power to do that. 

Speaker 9 (54:42):
Fascinating talk. Thank you very much. Just wondering whether fecal transplants really work if your biome changes all the time and if you transplant a different fecal thing into your body, would it reject it or would it accept it? 

Speaker 1 (54:55):
Yeah, very, very good questions too. So fecal transplants, for those of you, just to lower the tone ofor this evening, for those of you who haven't come across them, is the idea that you could take someone's healthy gut microbiome and infuse it into um, uh, your own intestine, replace your microbiome and, and you will get health benefits. So there is really, really good data that that works for some selective, uh, uh, situations. So, uh, there is some evidence for Crohn's disease for example, there is very good evidence that if you have a, um, a clostridium difficile infection that is not shifted by antibiotics, um, that that replacing the microbiome can help in that instance. And there are various trials underway for things like ulcerative colitis and other gut health things. And I suspect the answer will be yes, um, for those conditions. It you are absolutely right that it is not trivial to make that microbiome take. 

Speaker 1 (55:44):
Um, so quite often you put in the microbiome from the donor, um, having got rid of all the bacteria in the host originally. Um, and it still doesn't stick if you like. We don't really understand the reasons for that. We suspect it's something about the interface between your immune system and the gut and those bacteria coming in, they're recognized as foreign and ejected, but we don't quite know that. Do I think, and the implications do, I think you could start to manipulate people's behavior with this that starts to get very interesting. Um, and you might be familiar with the fact that there was a, a court case, for example, in the US at the moment about someone who received a fecal transplant for, uh, disease purposes. Um, uh, but then afterwards started to get obese and it turned out that the person they had had the fecal transplant from was obese. 

Speaker 1 (56:23):
Um, and so they are saying this, you know, you've given me a dodgy drug here and I'm obese cause my microbiome's doing it, not because I'm eating too much. Um, and that starts to get to a very, very thorny issue of rights and responsibilities. Um, but you can easily imagine a scenario where we might want to pre-screen fecal donors for their mental health, for example. Um, because you probably don't want to have a microbiome that might be more associated with, uh, you know, uh, I dunno, paranoia or anxiety or something. Uh, there are lots and lots of tricky ethical grounds there, and at the minute I think the science is way behind that. But I, I could imagine that 20 years from now someone might be standing here saying, God, of course we do that. You know? Um, wait and see. I guess 

Speaker 2 (57:01):
Thank you so much for your questions everyone. The last lecture in the series, A microbial future will take place on the 10th of May. So we hope you can all join us then. Thank you very much everyone.