#234      27 min 26 sec
It's alimentary: The brain, the gut's nervous system, and links to autism

Neuroscientist Dr Elisa Hill and Gastroenterologist Dr Kent Williams discuss the complex interactions between our brain and neurons found in the gut, and consider the over-representation of gastrointestinal disorders in children with autism. Presented by Dr Shane Huntington.

"What we've seen is that there are similarities in changes, such as the hypothalamus and pituitary-adrenal axis in children with autism and gastrointestinal disorders that we don't have a physiological or tissue cause for it." -- Dr Kent Williams




Dr Elisa Hill
Dr Elisa Hill

Dr. Elisa Hill is a Research Fellow in neuroscience in the Department of Physiology, University of Melbourne. Together with colleagues at the University of Melbourne, the Florey Institute for Neuroscience & Mental Health and Ohio State University, her work investigates how neurons function in Autism spectrum disorder (ASD). Dr Hill is also a founding member of the organising committee for BioAutism conferences, which aim to showcase top quality scientific research into biological causes of autism in an accessible way. ASD refers to a broad range of disorders that affect 1 in 88 children. Children diagnosed with ASD show impaired communication and social interaction skills together with restricted or repetitive behaviours. Patients with ASD commonly show additional traits such as sleep disorders, anxiety, motor difficulties, seizures, sensory issues and problems with gastrointestinal function. The cause of ASD is unknown. However, studies in twins and siblings have shown that genetics can play a role. Many genes associated with ASD code for molecules located at synaptic junctions between neurons and are important for normal brain development and function. Dr Hill and colleagues are studying behaviour and gastrointestinal function in a mouse model of autism expressing a gene mutation identified in patients with ASD.

Dr Kent Williams
Dr Kent Williams

Kent Williams, MD, is an attending pediatric gastroenterologist at Nationwide Children’s and an Assistant Professor of Clinical Pediatrics at The Ohio State University College of Medicine. Dr. Williams’ clinical interests involve all aspects of pediatric gastroenterology, with a special interest in GI disorders in children with autism spectrum disorders. As an investigator at the Research Institute at Nationwide Children’s and OSU, he conducts basic and translational research into the mechanisms that cause functional gastrointestinal disorders, such as abdominal pain, constipation, and reflux, in children with autism. In 2012, Dr. Williams became co-chair of the Autism Treatment Network’s gastroenterology committee, a national work group that is responsible for establishing guidelines and recommendations for treatment of GI issues in children with autism spectrum disorders.

Credits

Host: Dr Shane Huntington
Producers: Eric van Bemmel, Kelvin Param
Associate Producer: Dr Dyani Lewis
Audio Engineer: Gavin Nebauer
Voiceover: Nerissa Hannink
Series Creators: Kelvin Param & Eric van Bemmel

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VOICEOVER 
Welcome to Up Close, the research talk show from the University of Melbourne, Australia. 

SHANE HUNTINGTON 
I’m Shane Huntington.  Thanks for joining us.  You may know autism as a complex neurological condition that affects social interaction and communication, and can cause those with the disorder to engage in restricted, repetitive or aggressive behaviour.  But what's less well known is that children with autism are far more likely than non-autistic children to experience gastrointestinal disorders.  We know today that there is a complex interaction between our brains and our gut, but the details of how and why gut function is altered in children with autism is still being teased out.  In this episode of Up Close, we speak to a neuroscientist and a paediatric gastroenterologist, who are working to understand the connections between the brain and neurons in the intestines of autistic children.  Dr Elisa Hill is a research fellow in the Enteric Neuroscience Group at the University of Melbourne's Department of Physiology, and Dr Kent Williams is a paediatric gastroenterologist at the Nationwide Children's Hospital in Columbus, Ohio, and assistant professor of clinical paediatrics at the Ohio State University College of Medicine.  Welcome to Up Close, Elisa and Kent. 

KENT WILLIAMS
Hello. 

ELISA HILL
Thanks for having me here. 

SHANE HUNTINGTON
Elisa, I'd like to start with you.  We've covered autism in a number of previous episodes on Up Close, but it would be good to just give a brief outline of what autism is, specifically in children, and what sort of things you would see in a patient with this condition.

ELISA HILL
Okay.  Well, autism is quite complex, and it's quite different in any individual that is diagnosed.  But the basic features are reduced social interaction, reduced social communication, and a tendency for repetitive behaviours.  Along with that, there are a number of comorbidities or other traits that seem to pop up; the kids often have sleep disorders, they are more likely to have seizures, a number of other things.  But also, gastrointestinal problems are seen in children with autism. 

SHANE HUNTINGTON
Kent, what sort of interventions are there currently for children in particular that have autism? 

KENT WILLIAMS
Well, for me, I treat children with gastrointestinal problems, so if you're talking about those, there's not much different than what we do for, say, children without autism.  The overall treatments for autism itself, though, are behavioural therapy, interventions for those, and there are certain medications that people will use.  Those aren't particularly the ones that I focus on.  When someone comes to me, it's primarily for treatment of a gastrointestinal problem and evaluation for the causes of those.

SHANE HUNTINGTON
Elisa, do we have an idea at this point of how much autism relates to genetics and how much it is caused by environmental factors, or is that still a complete unknown? 

ELISA HILL
I think that's a really complex issue, but certainly studies in twins and siblings have shown that genetics do play a role, and it's now becoming clear that there are over a hundred genes that are associated with autism.  A number of these genes seem to have similar functions, in that they seem to be related to the way neurons communicate, and they are responsible for autism in a very small number of patients in the population.

SHANE HUNTINGTON
Kent, when we look at autism and then we start talking about these digestive problems, can you bring these two things together; why is there such an interest in digestive problems in children in particular with autism?

KENT WILLIAMS
Well, what's interesting in how people are approaching the mechanisms of autism is looking at a comparison with how people are looking at the mechanisms of intestinal problems in non-autistic children and in adults also.  There's a whole field of interest in what's called the brain-gut axis within the research of intestinal problems.  What is interesting is when you look at that brain-gut interaction, what people don't really realise is that the amount of neural tissue that's in the gastrointestinal system is equivalent to about what we find, like, say in the spinal cord, and the same type of neural transmitters that we see in the brain and the spinal cord we see in the gut also.  So, when you have something that alters the function and the way the nerves communicate with each other in the brain and the spinal cord, it's going to have an impact, most likely, on the gut also.  
What we've seen is that there are similarities in changes, such as the hypothalamus and pituitary-adrenal axis in children with autism and what we call functional GI disorders - basically, that's gastrointestinal disorders that we don't have a physiological or tissue cause for it.  But there's differences in the stress response, there's differences in associations with stress and anxiety, and there's differences associated with sleep in children without autism.  What's interesting is when you look at the autistic population, stress, anxiety, sleep, changes with stress responses and things are very common and very much studied.  So, if someone is to ask why you think there is such an association, the question to me would be more, why would you think there's not, considering that the same mechanisms that are being looked at in autism as what we see in children with functional GI disorders. 

SHANE HUNTINGTON
Now, presumably many of these disorders are ones that you and I and everyone else would have at some times in their life.  Is there anything specific that we see that you only get in children with autism, or is it just that same range of anxiety-based disorders and so forth that you get in the general population?

KENT WILLIAMS
Well, what's interesting with the work that we've been doing associated with what's called the Autism Treatment Network, which has 17 centres throughout North America, is that what we're seeing is that constipation is probably the most common disorder, and so there's a lot of associations with constipation that we see in children with autism.  It is associated probably with stress, anxiety and different sensory perceptions and things like that, that are more common in children with autism than what we see in children without autism.

SHANE HUNTINGTON
Do you see a correlation between how extensive the level of autism is in the child and the level of these disorders in those children, or is it somewhat random?

KENT WILLIAMS
That's a very good question.  So far, in the data that we've looked at where we've studied roughly upwards of around 3,000 children and gotten responses from parents and screenings of GI disorders and stuff, we are not seeing a difference between the different types of autism.  Whereas classical autism is considered to be more of a severe form of autism and Asperger's being considered less severe, there's no difference in the rates of chronic GI problems across those diagnoses.  Most people do not see, necessarily, a change either in the functions such as with IQ.  Now, there is some data out there saying that there might be differences in the children who have verbal expression impairments; for instance, those that have less verbal expression may be more likely to have constipation.  There is some preliminary data out there, but that's yet to be proved out.  But that's the only area, really, where we see, like, a difference in the severity of the disease.  Otherwise, all children across all spectrums - I'd say the rates are somewhere around 30-40 per cent, is what we're seeing within our own data. 

SHANE HUNTINGTON
Do you think there is a correlation between the issue of a child knowing when to go to the toilet, when to eat, when to do these various things, and these disorders?  Or is it more linked to this gut-brain link that, I guess, is not something they're aware of?  So, is it the behaviour or is it inherent to the problem of autism itself?

KENT WILLIAMS
Right now, we don't know. When you're talking about brain-gut interactions and the communications that go on between these different levels of the central nervous system and the enteric nervous system - the gut's own nervous system - it's hard to know exactly where the breakdown occurs in the individuals.  When you're talking about behaviours, is behaviour completely separate or is it part of the changes that you see due to a neurological make-up?  So, I think trying to separate both out from each other is incredibly hard to do for one thing, and then the other thing is, most likely, when you change brain-gut function, we know we're going to change behaviours also.  If changing behaviours can change brain-gut function, it's hard to know - but we know there's a high correlation between gastrointestinal problems and, let's say, anxiety, depression, and those things.  So, in the children with autism, whether it's due to that they have a difference in perception or they have a difference in their responses to cues that they have, we don't really know at this point in time. 

SHANE HUNTINGTON
I'm Shane Huntington, and you're listening to Up Close.  In this episode, we're talking about the gut function in children with autism with neuroscientist Dr Elisa Hill and paediatric gastroenterologist Dr Kent Williams.  Elisa, normally when we speak to a neuroscientist, we're talking to someone who examines what we have inside of our skull, our brain, but you are working on the gut.  How is it that a neuroscientist ends up working on this part of the body when we normally would be working on the brain itself?

ELISA HILL
Well, basically, you know, we can think of it as the mini-brain, and there are neurons in there interacting via synapses - the junctions between the neurons - and there are a lot of similarities.  Neuroscience also includes the enteric nervous system in the gut.  Where my work takes on after what Kent does when he sees patients is to take the gut in isolation and look at the nuts and bolts; the mechanisms by which the neurons are communicating in that nervous system.

SHANE HUNTINGTON
When we talk about this at sort of an individual nerve cell level, I mean, what is going on in terms of autism, whether it's in the brain or in the gut? 

ELISA HILL
A really great question - it's really complex.  What we have are these specialisations - they're like, if you like, sticky points between neurons.  They keep them adhered and in close proximity so neurons can communicate, and there are lots of molecules that help these neurons remain in position.  I mentioned before, there are a number of genes associated with autism, and many of these seem to be really important in adhesion at these junctions.  So, it looks like some of these gene mutations slightly alter the function of the synapses, or the region where the neurons communicate, and that seems to just put things askew and the brain is not quite functioning, or the gut nervous system may be slightly - the function might be slightly different. 

SHANE HUNTINGTON
When you look at something like autism, I mean, is there a difference between where you grab your sample from in this case, whether it comes from the person's brain or their gut?  Do you see - I mean, I know you don't work specifically on people and on brain models. 

ELISA HILL
I definitely don't take samples from people.

SHANE HUNTINGTON
But, you know, would you be able to tell where that cell came from in terms of how these problems are presenting themselves? 

ELISA HILL
Well, certainly there's a really different way that the neurons are arranged in the cerebral cortex, for example, where they're much more tightly packed and you have six layers, for example, quite organised.  Whereas, in the gut, you basically have a tube of muscle and you have two different mesh-like layers of neurons, and they are basically involved in controlling the motility of the gut or the secretion.  It's not quite that simple, but it's a really great system to be able to look at those functions, which are controlled by neurons.

SHANE HUNTINGTON
When we talk about interventions - pharmaceutical adaptions to autistic children - do we have an idea of how these pharmaceutics actually affect both the gut and the sort of brain and head?  I mean, or are we just looking at one of the two and not really thinking about the other half?

ELISA HILL
Quite a lot of work has been done looking at kids' behaviour, and there are medications that assist in irritable behaviour and so on.  But what we're doing is looking at the gut in isolation, and look, that's a great preparation.  We can dissect out that gut tube, place it in a saline bath, and what's very nice about this assay is that the gut contracts on its own for about three hours, at least three hours after being isolated from the animal.  We can then add various drugs, and some of those are those drugs that are used in the clinic, and look at how they might be interacting on gut function in that system.  So, that's very exciting and we're actively doing that kind of work at the moment.

SHANE HUNTINGTON
Kent, you may want to respond to this as well. 

KENT WILLIAMS
So, in the clinical work, no one has really looked at what the effect is of these medications on the gut themselves.  I mean, the primary problem that people are trying to treat usually is the behaviours, whether they be self-injurious behaviours, aggression behaviours, or problems with social or verbal skills and things like that.  So, what people usually focus on for the medical treatments with those are what medicines help those behaviours.  When it comes to the gut, we use a totally different type of medications a lot of times - stool osmotics and different things to help treat for constipation and those things that don't have anything to do with a lot of the behaviours, per se, of treating neurons or things like that.  But what I do find interesting is, most medications that are used tend to probably alter gut function to a certain degree.  Now, each person is different.  Some medications will tell you, if you look up their side effects, some will say it causes constipation and then in a certain percentage it causes diarrhoea also.  So, the medications definitely do have either an advantage or a disadvantage at times within the gut. 

SHANE HUNTINGTON
When we talk about the communication that's occurring between the brain and the gut, I guess many of our listeners will understand the communication that occurs between a person's brain and their hand when they move it, or their foot when they walk.  I mean, how does this sort of communication compare to that?  What are we really talking about here in terms of that interaction?

KENT WILLIAMS
Well, the type of communication you're having between your brain and your hand is, basically, you're aware of that.  There's a whole nervous system, though, where's it's autonomic; it goes on without us even thinking of it.  It's the same nerves that help control your heart rate, your blood pressure, your breathing and all those things.  Even though those nerves go from the brain to those different organs, there's nerves that go from those organs back to the brain.  In some people, we do know that there's strong evidence showing that the sensation, so to speak, from the gut is altered in those with, say, irritable bowel syndrome.  There have been studies where they will stretch the intestine in people who have irritable bowel syndrome versus those who don't, and those who have irritable bowel syndrome will be able to feel the stretching at a much lower threshold.  Now, it's not something that they're aware of, but perceptions come to the consciousness, and those, at the time, is where they can cause impairment to someone's life, that they're feeling it and interpreting it as pain. 

SHANE HUNTINGTON
So, going on from that, when we talk about the influence of sort of behaviour and mood from our gut function and vice versa, I mean, what sort of things are you seeing there?  We often hear about anxiety making people feel unwell and so forth, but are we sure about that at this point? 

KENT WILLIAMS
We know the associations are real.  What the connections are and the mechanisms are is very unclear.  So, we know that people who have chronic pain are more likely to develop depression or anxiety, and in children, the difference between anxiety and depression is basically two sides of the same coin; some kids appear to be very anxious, and depression behaviours are very similar.  So, we've known that in children who have anxiety and depression, they're more likely to have gastrointestinal problems.  Now, that's not to say, if you're a very anxious or depressed person, you have GI problems.  It's just that you're more likely to have - it's an increased association.  But what is causing the connection there, no one knows for sure at this point.  The theory would be that there's some common underlying - either some kind of problem within the brain itself, or there's certain centres not communicating well within the brain or whatever that's causing both; that there's one common underlying cause. 

ELISA HILL
I guess I could add to that that there has been a lot of reports about the microbiome recently, and I mean, the mechanisms haven't been worked out, but it's known that bacteria can actually produce toxins.  They can also produce neurotransmitters, and if you imagine the bacteria is there in the colon, it's in close proximity to neurons; these neurotransmitters could, in effect, change the way the gut is acting, and then, of course, that can be part of the relay system back to the brain.  So, it's a possible mechanism by which the microbiome changes could have an influence. 

KENT WILLIAMS
Exactly.  I mean, we know the interactions and associations are there, but if one is more prevalent and affecting the others, we don't know at this time.  But they definitely interplay.  So, again, the microbiome would be one way of showing that there's strong communication from the gut to the brain.

SHANE HUNTINGTON
I'm Shane Huntington, and my guests today are neuroscientist Dr Elisa Hill and paediatric gastroenterologist Dr Kent Williams.  We're talking about the links between autism and the intestinal nervous system here on Up Close.  Elisa, let's get back to the idea of using a mouse model, for example, to investigate some of these things.  When you look at autism, characterised by the sort of behavioural aspects of children in particular, how do you go and identify such characteristics in mice?

ELISA HILL
Yes.  This is a common question, and actually, it's quite well established now that there are a number of mouse models, and people have designed a number of tests that can be done to check out to see whether these mice have behaviours that might be similar to autistic behaviours in children.  So, of course, you can analyse social interaction - mice are actually very social animals - you can use a videotape of just free interaction time, or you can have a more complex setup where you have different chambers and you might have, for example, a novel object or another mouse in a contained area, and look at how your mouse - whether it may be carrying an autism mutation or not - interacts with another mouse, for example.  
That can tell you something, and a number of models have shown reductions in that kind of social interaction, and these mouse models can also express genetic mutations that have been found in children.  We can also look at - this is interesting - communication.  So, in the ultrasonic vocalisations, mice do communicate and it's been shown that a number of autism mouse models also have reduced communications.  It's a very complex area, and the analytical software is not perfect yet, but we do see reduced calling, for example, when mothers are taken away from pups, say in the early weeks postnatally.  Also, repetitive behaviours, which is another hallmark seen in the children - what mice tend to do is groom, and groom incessantly, so they can actually create bald patches or groom until they're bleeding.  
But even if it's not as severe as that, we can look at things like compulsive digging in the cage, and this is all recorded and analysed off-line, blind to the mouse gene mutation genotype.  So, these are three main things, but then, of course, there are lots of other traits that we see - other behaviours that we see in children - that can also be looked at in some shape or form in mice.  People are looking for seizure susceptibility, for example.  Of course, we're looking at the gastrointestinal function, and you can even record EEGs and look at sleep patterns, which is interesting as well.  So, there are a whole number of ways that you can validate these models, and the field is really going forward at a really fast rate.  

SHANE HUNTINGTON
These are mice that have been genetically bred specifically to have these characteristics, so we must know a certain amount about the role played by specific genes.  Is it just a gene or is it a number?  Do we know that interplay and how many are involved?

ELISA HILL
No, we certainly don't know that at this point.  What we know is that the genetics are complex, but for a small number of patients, they are single-gene mutations that, if you have them, you will have autism.  So, in a very small number of cases - and these are generally the cases that these gene mutations are taken and a mouse model is created, and researchers can then study that. 

SHANE HUNTINGTON
When we talk about testing the gut function or looking at gut function in the mouse, this isn't something they can tell you about.  So, how do you go about addressing that? 

ELISA HILL
So, the way we have been looking at it is to isolate the gut and to look at the contractile properties, and these can be altered by adding various drugs and so on, to look at that.  We can look at baseline - so, we don't do anything to the gut, it's just in the saline and contracting, and we can check whether or not that specific gene mutation associated with autism changes the baseline function.  We can also perturb the system and add drugs, and see if that changes the way the gut contracts, and that's the direction we're going in at the moment.  There are a number of other things we can do.  We can look at how long the transit time is, for example, in mice; so, we feed the mouse something containing a food dye, we time how long it takes for that to travel through the intestinal system.  
We're also looking at how these animals react to stress, because collecting faecal pellets, for example - generally you would collect more faecal pellets from an animal that is stressed.  We might expect that in our animals - we heard Kent talk about the anxiety that's present in a lot of children with autism - we might expect that they're more susceptible to stress conditions and produce more pellets or have changes in their pellets.  We can also go further and analyse pellets for bacterial content, and that's going back to that microbiome issue.  There are a whole range of other techniques.  These are the main ones that we're looking for.

SHANE HUNTINGTON
So, you have this great control over the dietary input and what the effects are.  Kent, coming back to you, do the studies we're doing in mice with regards to autism further support the connection between GI and autism that we are looking at in kids? 

KENT WILLIAMS
Yes, it does, because what we're seeing in these mouse models are not only changes within the central nervous system, but we're actually seeing changes in the nervous system within the gut, which I think really supports the idea that this is just more than beyond GI problems due to behaviour in children with autism; that there's actually neuronal changes at the cellular level that are going on, that's contributing to gastrointestinal problems. 

SHANE HUNTINGTON
We know that diet does affect gastrointestinal disorders.  What sort of things can you do for autistic kids in that regard?  Is it possible to reduce these problems with their diet? 

KENT WILLIAMS
Well, that's a very interesting question, and one that is under a lot of scrutiny and controversy in itself.  There's no real good studies looking at the actual, like, blinded control studies of, if we're giving you this diet, your behaviours improve - because the problem is, a lot of these diets that people implement are very altered diets, restrictive diets.  So, as you could imagine, if you're - especially if you're, let's say, on a dairy-free diet, which would be a simplistic one.  If you're on a dairy-free diet, knowing that you're not on certain milks or cheeses and things, a kid would know, plus the parents would know.  So, it's hard to ferret out how much is really due to the diet or is this due to a placebo effect, that they expect the changes to happen there.  
With that being said, though, there is definitely so many parents who do see changes - not only in their behaviours, but let's say in gastrointestinal function, the kids improve from constipation and things like that.  Within the field of functional GI disorders that I was talking about earlier, what's interesting to me is, there's a lot of interest now in using diets to treat that; treating functional abdominal pain, irritable bowel syndrome.  What's very fascinating to me is, the type of diets that are being used for that are not a lot different than the diets that parents are using in kids with autism also.  Now, what we're not seeing is that there's a complete reversal of autism and all behaviours go away, or anything like that.  
But we definitely can see some improvements in quality of life, I believe.  What I would definitely strongly encourage people, when they go on these diets, is that they work closely with somebody like a nutritionist or a dietician making sure that the nutritional needs are being met, because a lot of these kids are already restrictive in themselves.  They're picky eaters - or even kids without autism.  We all know a three to five-year-old that they live on peanut butter and jelly, and mac-and-cheese, and you know, it's the same with kids with autism and even more so at times.  So, I always want to make sure that, if we're restricting diets, that we try to make sure that we're meeting the minerals and the vitamin needs - the micronutrients of the kids.

SHANE HUNTINGTON
So we have the autism, we have the brain-gut interaction, and we have these dietary intakes; how far up that chain does the sort of change in diet affect things?  I mean, do you see changes in the autistic behaviour as a result, or just in the digestive problems?

KENT WILLIAMS
Again, no clear science on that at all.  Parents definitely report that they see differences in ability to concentrate, differences in aggression, differences in self-injurious behaviours, verbal skills improve.  Parents report that; there's no strong data supporting those findings at the time of things like that.  The problem too, is, going back to the microbiome, where are the changes occurring?  Is it due to the nutrition that you're taking in or is it that you're changing the type of bacteria and the environment that's within the gut, that's producing different changes in inflammation, irritation and neural transmitters?  We don't know right now.  We don't have enough information to know if changing a diet - is it just because you're having different nutrients going in that, like, you have brain food that helps development and function of the brain, or are you changing environments and just the overall wellbeing of the child? 

SHANE HUNTINGTON
Elisa, just finally, as a neuroscientist - I mean, you're obviously focused on the gut here - you must have an interest in this being used as some sort of particular way to find a good intervention for autism.  What is the expectation there, that we'll be able to do something serious with diet or with gut function to minimise the effects some of these children are feeling?

ELISA HILL
Well, I think where we are at the moment is looking at what's happening at the level of the gut and promoting some awareness, perhaps, that the enteric nervous system in itself could be altered in some children that have specific gene mutations.  I think, perhaps in the long term, if that awareness is forthcoming, perhaps clinicians are going to think more about that, and when they see - a paediatrician, for example - when they see an autistic child, they might consider testing for GI in any case, if the behavioural problems are evident.  Of course, we can look at how different drugs are interacting with the enteric nervous system, and maybe that will have implications for other treatments that are already given to children with autism or anyone with gastrointestinal problems.

SHANE HUNTINGTON
Dr Elisa Hill, research fellow in the Enteric Neuroscience Group at the University of Melbourne's Department of Physiology, and Dr Kent Williams, paediatric gastroenterologist at the Nationwide Children's Hospital in Columbus, Ohio, and Assistant Professor of clinical paediatrics at the Ohio State University College of Medicine - thank you both for being our guests on Up Close today, and talking to us about the research into links between autism and gastrointestinal disorders.

KENT WILLIAMS
Thank you.

ELISA HILL
Thank you.

SHANE HUNTINGTON
Relevant links, a full transcript and more info on this episode can be found on our website at www.UpClose.unimelb.edu.au.  Up Close is a production of the University of Melbourne, Australia.  This episode was recorded on 31 January 2013.  Our producers for this episode were Kelvin Param and Eric van Bemmel, associate producer Dyani Lewis, audio engineer Gavin Nebauer.  Up Close is created by Eric van Bemmel and Kelvin Param.  I'm Shane Huntington.  Until next time, goodbye.

VOICEOVER
You've been listening to Up Close.  We're also on Twitter and Facebook.  For more info, visit www.UpClose.unimelb.edu.au.  Copyright 2013, the University of Melbourne.


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