Outnumbered: Are your bacteria controlling you?

Humans do it. Primates do it. And now it's been found out that birds can also do it:  3-day-old chickens have been shown to order numbers - low to high - from left to right - just like on a ruler! The findings, published in the journal Science, could indicate that this numerical ability is a feature of evolution, rather than culture - and could help explain why we pay more attention to things presented on our left... Zoologist Hannah Rowland from the University of Cambridge put Graihagh Jackson's numerical skills to the test...

Hannah - Plenty of people have been very interested in whether counting is a uniquely human behaviour. Lots of research has been done to figure out if animals have a sense of number. A really famous one that all students are taught is that peahens like to mate with peacocks that have about 150 eyes in their tail. If you take about 5 eyes out, the male peacock becomes far less attractive to the female. Now, people might think she is standing there going, "1,2,3,4..., 149, 150." But to actually tell the difference between a tail that has a 150 eyespots and 145, she doesn't have to count. So, she can pay attention to the asymmetry of the tail, or the density of spots in their tail. And so, while it might look like she's counting, she doesn't have to actually count at all.

Graihagh - Is there any way that you can tell if an animal can count because I imagine it's quite hard to disentangle what you're talking about and also, the whole, 1, 2, 3, 4, 5, 6, 7, 8?

Hannah - So, to actually test whether animals can count, you have to look for whether they can pay attention to the order of numbers or dots, or symbols. And there's lots of research been done on this with primates.

Graihagh - What about birds?

Hannah - Birds can certainly tell the difference between patches that have a lot of items or fewer items, but that's not counting as such. That's more numerical discrimination.

Graihagh - Given that the paper looked at domestic chickens, we thought it only appropriate to go and see some chickens ourselves. The only problem was, they were very scared of us. So, we had to feed them a bit of my pack lunch to get them to say hello.

"Hello."

"Now, look they're eating the peas."

Graihagh - So, my lunch didn't go to waste then. What are these guys called? Are they named after the colours because they're beautiful colours? You've got a grey one and sort of very warm orange then a light orange and a black with flex of teal almost.

Hannah - So, the black one is called Brumble and the grey is called Teazel and the yellowy and the brown ones are Heather and Bracken. Yeah, it's after their colours.

Graihagh - Let's talk a bit about this paper. What about the idea that if they can count, there is a tendency to count from left to right, just like humans do?

Hannah - So, this paper that's come out in science, it's based upon research that actually was right back in the 19th century. So, Francis Galton was one of the first people to realise that when we think of numbers, we generally order them on a horizontal line so across the page and usually from left to right.  So maybe I can actually get you to do it.  So, think of a ruler. Think of where number 6 is in the position on the ruler. Now, I'm going to tell you a number. If the number is smaller than the number 6, I want you to raise your left hand. If it's larger than the number 6, I want you to raise your right hand. So, think of number 6, 8. Now...

Graihagh - I raised my right hand. I did it right?

Hannah - You did and you were really fast. Now, think of number 6. If the number I say is smaller, I want you to raise your right hand. If the number is larger, I want you to raise your left hand. 4...

Graihagh - I did have to think about it this time though. I raised my right hand, but I did have to think about it.

Hannah - Exactly! That's because it's much easier for people to order things that get larger so that grow in magnitude from left to right.

Graihagh - And that's the same in chicks as well then.

Hannah - Yes. It turns out that they show the same behaviour.

Graihagh - Imagine you're in a box. There's a card in the middle of the box which 5 dots on it. Behind it is a tasty treat. This happened again, and again, and again. A card with 5 dots is always in the middle. Then one day, there's two cards - one on your left, one on your right, both have two dots on them. Which one do you look behind for your tasty meal worm reward? Well, the chicks nearly always picked the one on the left. Maybe chicks are all left-winged. So, in the next tests, they added two cards with 8 dots on them - one on the left, one on the right, same layout, different dots. Guess what? They looked behind the right card for their reward. This shows that chicks like humans associate lower numbers on the left and higher numbers on the right.

Hannah - In humans, we know that this is because the right hand side of our brain is very dominant. So, we pay attention to the left hand side of pictures. This seems to be the same in chickens as well.

Graihagh - I find this quite surprising that we share this attribute with chicks because surely, that means that the reading of numbers from left to right isn't a cultural thing. It's built in us because we split from birds 300 million years ago or something. Why might we share this with birds?

Hannah - Well, I think that's a question that those researchers are still going to try and find out. It may be that we have some very ancient shared ancestry where the wiring of our brain is very similar way back in evolutionary history.

One in five violent offenders are what psychiatrists would describe as psychopaths. They're callous, unemotional and from childhood show violent tendencies. They're also responsible for a disproportionately large amount of crime.  But a big problem dealing with psychopathic criminals is that punishments - like prison - usually offer no deterrent to re-offending. Now Nigel Blackwood and his team at Kings College London, have discovered that this may be because their brains are wired up differently. He explained to Kat Arney what defines a psychopath... 

Nigel - Psychopaths are individuals who have been involved in anti-social behaviours across their lifespan. They're conduct disordered as kids with what we call callous-unemotional traits and grew up to be adult psychopaths. So, in common with the broader anti-social group, they have a lifespan history of impulsivity, risk-taking behaviours, poor decision-making. So, they lack in empathy. They're callous. They're interpersonally manipulative. They use aggression in an instrumental way to get what they want.

Kat - What's the wider impact to society of these kinds of people?

Nigel - So, the broad anti-social group, a small number of men are responsible for the vast majority of offending behaviours in our society today. That psychopathic subgroup are likely to start offending earlier have a higher frequency of offending behaviours, and are most likely to re-offend when they're released from prison. So, that's a very important group to try and intervene in.

Kat - How did you go about in trying to study this group of people in more detail?

Nigel - So, there's plenty of studies that look at the differences between psychopath's brains and normal subjects in the community. But if we really think there's something important about psychopathy, we've got to show that there's differences between people who are antisocial and psychopathic and those who are antinsocial are not psychopathic. So, we looked at 50 men, some from the community, and the vast majority of coming out of prison and to being looked after in probation services. We made sure that they had violently offended in the past, so they've been involved in murder, attempted murder, GBH, rape, and then decided whether they were or were not truly psychopathic. And then we looked at the differences in those three groups in our brain scanner.

Kat - What did you find that was different between them?

Nigel - Well, I suppose there's a folk idea that the psychopathic group don't respond to punishment, just because there's reduced sensitivity to punishment. They have years of being punished by their parents, by their teachers, by the prison system, and they just don't respond anymore. But that isn't what we found. So, we found at the moment at which the psychopathic group were punished in a task which involved reward and punishment, they showed increased activity in areas that track such information. So, they're not just reduced in the sensitivity to punishment. There's something fundamentally different about the way they process punishment information.

Kat - To play devil's advocate slightly, if this is something that's just intrinsic in the way someone's brain is wired up, you're wired to be a psychopath, why don't we just keep them imprisoned forever?

Nigel - Well, we know that this subgroup are more genetically vulnerable, but we shouldn't pessimistic at this stage that these kids are doomed from the womb and we've got to preventatively detain them. What we need to be trying to fix is changing the treatment programmes. And I think we can maintain at least some sense of therapeutic optimism about our approach to such people.

Do you consider yourself human? We hate to break it to you, but your human cells are outnumbered by the millions of microbes living in you and on you.

They're what are known as our microbiome, and recently researchers have started to realise that these multitudes may be having an effect on our health, weight and even mood.

To learn more about these microbial friends, how they get there and what they're doing, Kat Arney spoke to science writer Ed Yong to get the basics...

Ed - People think of themselves as individuals, as a single animal. But actually, every one of us is an ecosystem - inside our bodies and on our skins. We have trillions of bacteria and other microbes that live with us, that influence our lives. They aren't just mere hitchhikers or passengers. They are integral parts of our bodies. They do things like help us to digest our food. They protect us from other deadlier microbes that threatened to cause diseases. They help to shape our immune systems and perhaps even our behaviour. They're very much a part of us.

Kat - I guess that bacteria have a bit of a bad rap because we always think of them as causing diseases. How recently did we get this alternative view of them that actually, they may be a really important part of our lives?

Ed - I think people have known that for actually a very long time, but it's been quite a neglected concept. So, even people like Pasteur had some appreciation that microbes could play a beneficial role. But you're right that we've come to think of microbes generally as causes of diseases. So, you get endless news stories saying, "Your mobile phone or your keyboard has more bacteria on it then a toilet seat. The implication there is that bacteria are a sign of death and filth that there are bad things that you want to get rid of and destroy. Whereas that's just not true. There are obviously microbes that make us sick. But there are probably many more that actually help us or at worst, are completely neutral. Bacteria had the planet to themselves for billions of years before any human or any - even an animal came on the scene. So, we live in their world and we have evolved in their world.

Kat - If you say that bacteria are found all over me, my skin, in my gut. Where did they come from?

Ed - It's generally thought that people are born sterile so that the womb is a sterile bubble in which it's just the baby. Now, that may or may not be completely true, but the fact remains that most of a child's bacteria are seeded into it when it emerges from its mother. So, not to put too fine a point on it, when your born, your slathered with microbes which then become yours. They colonise the rest of you. They get in your mouth. So, you get them from your mum basically. A lot of animals do that. some inherit microbes while they're still an unfertilised egg. Some get them at the point where they're born. Others eat them from things that their mothers provide.

Kat - We see in the news there are good bacteria and bad bacteria. Is this a fair definition? I look at my hand. It must be covered in bacteria. How do I know which one's a good and bad?

Ed - So, I think some bacteria, you could reasonably classify as bad. So, Yersinia pestis which causes plague is probably bad, Bacillus anthracis which causes anthrax, again, I think you could call that bad. But in most cases, those definitions don't really work. Say, the bacteria that live in our gut, they play important roles in our lives, help to digest our food, but they can also revolt. If they get across the lining of the gut and enter the bloodstream, they can cause really strong debilitating immune reactions. so, the same bacteria can be good in one setting and if you translocate them by about a few millimetres, they can suddenly be bad and dangerous. So really, these concepts of good and bad, they are dependent on place and time, and context.

Kat - And recently, as we've heard a lot about gene sequencing and people reading the gene sequences, the DNA sequences of different bacteria, the microbiome, what sort of stuff is starting to emerge from these studies because we hear a lot about them and it's hard to know what do they mean?

Ed - It's clear and increasingly so that bacteria do play important parts of our lives and I don't think it's hype to say that and to emphasise it. we are used to thinking of ourselves as individuals that we live under our own steam, we behave under our own wills, we grow up from a single egg into this complicated organism under instructions from our own genomes. All of those things are complicated by the presence of bacteria. So, we know that bacteria shape our development, they shape our behaviour, they shape our physiology, but we also know that bacteria affect our health. So, lots of studies have compared healthy people and people with diseases or various health problems from obesity to diabetes to colon cancer, and compare to their microbiomes to those healthy people. And they found differences. Now, what this means is still unclear I think. In some cases, we've got better evidence that the bacteria are behind those conditions. But in others, it's not clear whether the changes in the microbiome are just going along for the ride, whether they're the results of the condition rather than the cause of that.

Kat - Are someone's gut bugs making them fat or because they're fat, they have different gut bugs?

Ed - Exactly or probably a cycle of both of things. I think that's where there's currently a bit of hype. Microbiome has been linked to virtually every health condition under the sun now. People have written reviews saying, maybe the microbiome is behind religious behaviour or all sorts of aspects of human culture and behaviour.

Kat - It's just the bug.

Ed - That's right. everything is to do with microbiome. why did I feel sad on Tuesday? Microbiome! why do I crave a coffee right now? Microbiome!

Kat - We're just a vehicle for our bacteria.

Ed - We are and I think - well obviously, we're not. I think this is where the hype around the science goes too far. We need to drain it back in. what we need now is some careful science that looks beyond just comparing patterns in different people and establishes things like causality. What is actually result of the bugs or vice versa and how did they affect our health? What is the mechanism behind these things?

'I Contain Multitudes' by Ed Yong is out in 2016.

It's clear our bacteria play an important role in at least some aspects of our well-being. But have our modern lifestyles had an impact on the types of bacteria that live inside us? One way of looking at this is to consider the microbiomes of our ancestors; but bacteria don't tend to fossilise, which makes this a bit difficult. But Jessica Metcalf from the University of Colorado, Boulder, is not getting down in the dumps about it; or perhaps she is...

Jessica - What we can gain from studying the microbes that our ancestors had is to sort of compare it to what we have today and see what we're missing. So, we know that because of things like our widespread antibiotic use, intensive hygiene practices, and spending so much time indoors, and sort of our more high fat, high protein diet, that lack fibre, we've probably changed our gut microbiome substantially. And so, the question is, what did we use to have? How do we figure that out? One of the ways we can do that is by looking at the microbes that our ancestors had that's preserved in faecal material around the world. Faecal material is what we usually study to characterise a gut microbiome because when you poo, out comes all the microbes that are in your colon as well. And so, this gives us a really nice, easy way to understand what's in the gut. And so, we have been able to study faecal material from caves in North America and Central America, Viking latrines from England, and also occasionally, in naturally mummified human remains.

Kat - So, when you get a sample like this, how do you go about studying it? What are you looking for and how do you treat it?

Jessica - Because these faecal samples have been sitting around from anywhere from several hundred years, several thousands of years, we really worry about contamination. And so, we work with an ancient DNA lab - so, clean labs to help protect the samples from further environmental contamination and also, to allow us to really cleanly sort of remove the outer layer of these samples with like a Dremel drill and also with bleach, so that we just get the DNA out of the middle where it's most likely to have avoided contamination from soil or other environmental microbes.

Kat - What have you found out so far from studying these samples, from studying the DNA in them about what's different between our gut bugs today and those of our ancestors that live before us?

Jessica - We're finding some really, really interesting results. So, we're confirming our hypothesis that certainly, people living in western societies today are missing some microbes. And so overall, there's a lot lower diversity or number of microbes in our gut microbiomes. And so, we're finding that we're not only missing particular bacteria like a diversity of this whole group called treponema but also, different strains of bacteria that we do have, we just don't have as many different types anymore. Actually, one other really interesting finding is that it's not only the bacteria that we're missing but also, the microscopic eukaryotes. So, eukaryotes have nucleated cells like us, so eukaryotes, plants, fungi. But most eukaryotes are actually microscopic and we usually think of them as parasites. But some of these small microbe eukaryotes were probably beneficial or at least not harmful and we're almost completely missing those in western populations now.

Kat - I was going to ask, obviously, having loads of bacteria and parasites could be a good or a bad thing and we do have this assumption today that our modern life is terrible and making us sick. Do you think this difference in our microbiome from how it used to be to how things are today? For someone like me, I live in the city. Is this actually doing me harm and is it contributing to the kinds of diseases that do seem to afflict us more as modern humans?

Jessica - Well, I think the only honest answer to that is we don't really know. There are studies coming out that suggest that certainly, maybe some of the autoimmune diseases and sort of the effects on training our immune system by not having enough of these microbes may be a real phenomena. But this is incredibly complex and it's going to be really complicated to pick a part. But I think overall, we know that things like eating fibre increases the diversity of our microbes and that's most likely going to be a good thing.

Clostridium difficile is a nasty bacterium which causes over 10,000 infections per year in the UK alone. It leads to severe long-term diarrhoea and inflammation in the intestine and is a particular problem for the elderly and patients receiving antibiotics that wipe out their resident population of "good bacteria". What can be done about these infections? Recently, the idea of a faecal transplant, or "transpoosion" has been gaining traction. Microbiologist Brendan Wren, from the London School of Hygiene and Tropical Medicine explained the science behind the (rather unpleasant sounding) idea to Kat Arney...

Brendan - Well, it's quite an old idea from about 25 years ago. As you mentioned, Clostridium difficile is an organism that takes over the gut, when you take antibiotics and can cause severe disease and can be life-threatening. One of the problems is you get relapses over and over again. In desperate cases, because it's quite dramatic and desperate thing to do to try and re-establish the balance of your microbiota, is to have a faecal transplant. So essentially, to try to replace the bacteria that you've lost and re-establish the balance. Anecdotally, this has worked for quite a few years and more and more of these have been done worldwide and it's gaining traction as you mentioned.

Kat - Is this actually poo? I mean, let's do some details here. Sorry, if anyone's eating dinner. Is this poo? Which end does it go in and how does it work?

Brendan - It's poo so people may be able have their own or maybe their partners and more and more commonly now is the idea of poo banks around. So, within your own poo, you obviously have your own microbes and you need actually to start establish the balance. So yeah, it's literally that and it's in case in motion and it's given orally so it allows you to re-establish your gut microbiota.

Kat - This is kind of like a poo in a pill or sort of a poo shake?

Brendan - I guess more of a poo in a pill. I guess the issues with it are, you don't know what microbes you're putting in and potentially, it could be pointing some bad ones. Some countries, they do refuse to do it, but however, some patients are really desperate and Clostridium difficile can kill people. And back in 2004, 8,000 people in UK died. So, if you have a persistent problem with it, it's a desperate measure, but it's increasingly been used.

Kat - And you say it's increasingly being used, but what's the evidence that it actually works? Have there been clinical trials done of this yet?

Brendan - Some clinical trials have been done recently, but because it's such a desperate measure, it's hard to get higher enough numbers. So, it is more anecdotal. What we're interested in our research is we have a mouse model of Clostridium difficile and reinfection and we've been able to, in this day and age, as one of the speakers mentioned earlier, we can sequence quite easily so we can work out the content of the poo, and in terms of bacteria, that way, what we want to do is to get a magic cocktail if you like of bacteria that we know don't cause disease. With this cocktail, we'd be able to re-establish mark flow in a more defined approach rather than a poo pill.

Kat - Yeah, because it does sound kind of gross. I mean, we hear all the time about the adverts, the probiotics to help our healthy bacteria. Are people quite reluctant about the idea of either a poo transplant or a bacterial transplant in this kind of slightly more cleaned up way?

Brendan - What is a certain yuck factor about a poo  pill but people are desperate. If it's going to save their lives, they'll do it. that's why more and more of these have been done because Clostridium difficile has tripled over the last few years in our hospitals, particularly for persistent infections then it's one possibility.

Kat - Just very briefly to wrap up, we sometimes hear about the idea that maybe you could transfer poo from different people, share your microbiome and that might change other characteristics. For example, your weight or something like that. Is there any evidence on that very briefly?

Brendan - There's not really evidence yet on that. As your previous speakers mentioned, your microbiome being associated with everything to do with diet and health cancer, etc. But we're only at the early stages and I think with the new technology and being able to sequence the work of the actual bacteria there then we have more rational approach but I'm microbiome.

Kat - So, my cunning plan to find a thin person and extract some of their poo and then eat it is not going to work for me right now.

Brendan - I wouldn't recommend it.

Kat - It does sound fantastic. Are there hopes for larger trials for this in the future?

Brendan - Yeah, for certainly in the future and particularly in the US and lots of companies are setting up in this particular area. Poo banks will be around I'm sure. You'll have not just your genome sequenced but the genomes of your gut bacteria. So, it's going to take off I'm sure.