Chemistry World Podcast - March 2009

00:12 --    Introduction

02:03 --    Exercise capacity of heart failure patients improved        

05:00 --    Molecular thermometer takes cell temperature          

07:41 --    Steve Rimmer discusses creating smart wound treatments

14:12 --    New theory for nanotube growth

17:07 --    Combating high cholesterol using an HDL mimic

20:20 --    Nick Hewitt talks about atmospheric chemistry in the tropics

26:13 --    Natural Oceaniron fertilisation

29:17 --    Marine sponges show their age

31:55 --    The chemical conundrum - what is the substance used to remove sediment from Guinness

(Promo)

Brought to you by the Royal Society of Chemistry, this is the Chemistry World Podcast.

(End Promo)

(00:12 --   Introduction)

Interviewer - Chris Smith

Hello! Welcome to the March edition of the Chemistry World Podcast with James Mitchell Crow, Nina Notman, and Phil Broadwith and Matt Wilkinson.   Coming up, how to get more oxygen out of haemoglobin and into tissues, scientists have developed a compound that can do just that.

Interviewee - Matt Wilkinson

They used both healthy mice and mice that were genetically engineered to mimic mice that had severe heart failure and they showed that the more of the compounds delivered, the more both sets of animals could exercise up to 70% more in some cases. 

Interviewer - Chris Smith

And that agent might be very effective for the treatment of heart failure.   There will be more from Matt Wilkinson on that story coming up shortly.   Also how scientists are turning up the heat in cell biology with the new form of chemical thermometer.

Interviewee - Phillip Broadwith

This is some research coming out of Japan which is taking a fluorescent polymer gel injecting it into cells and measuring the fluorescence to tell the changes in temperature within the cell as it goes about its normal biological processes. 

Interviewer - Chris Smith

Phil Broadwith will be explaining how that temperature sensitive polymer works in just a moment.   Plus on the subject of polymers how scientists have made biological nets that can grab bacteria.  

Interviewee - Steve Rimmer

When those antibiotics attach themselves to bacteria, the polymer changes from, if you can imagine some, a sort of blanch piece of spaghetti that appears to collapse.   So this open system becomes a tighter collapsed coil if you like.  

Interviewer - Chris Smith

That's Steve Rimmer who's developing smart polymers who can change their shape when they meet a bacterium.   Hello I'm Chris Smith and this is the Chemistry World podcast.  

(Promo)

The Chemistry World podcast is brought to you by the Royal Society of Chemistry.   Look us up online at chemistryworld dot org

(End promo)

(02:03 --   Exercise capacity of heart failure patients improved)

Interviewer - Chris Smith

Heart failure occurs when the heart can't pump enough oxygenated blood to supply the needs of the body's tissues.   So far treatments have focused largely on trying to improve the heart's function to make up for the shortfall, but now there might be another way to combat the problem, by persuading haemoglobin to relinquish the oxygen it carries much more readily.   Tell us about this Matt.

Interviewee - Matt Wilkinson

Right well, researchers led by Jean-Marie Lehn the Nobel prize winner works at the Institut Louis Pasteur in Strasbourg has developed a cyclic pyrophosphate molecule known as myo-inositol trysphosphate or ITPP, for short which binds to the outside of haemoglobin, it is the molecule that carries oxygen around the body and delivers it to the muscle and organs so that they can live and basically it binds to the outside of the haemoglobin and subtly changes the oxygen binding pocket in the centre of haemoglobin such as that it would reduces ever so slightly by about 30% the binding affinity of the haemoglobin for the oxygen so that it can be delivered to those organs.

Interviewer - Chris Smith

So the haemoglobins giving out the oxygen more readily than it would do normally.

Interviewee - Matt Wilkinson 

Absolutely yeah, it still picks up the oxygen just as well from the lungs but the point is that when oxygen-starved-tissue comes into contact it releases that oxygen much more readily.

Interviewer - Chris Smith

Is this just tested, it has been done in the dish or have they shown this in animals that it really works in a living organism to make the haemoglobin behave like this?

Interviewee - Matt Wilkinson

Well they have actually done this in mice.   They used both healthy mice and mice that were genetically engineered to mimic mice that had severe heart failure and they showed that the more of the compounds delivered, the more both sets of animals could exercise up to 70% and more in some cases.  

Interviewer - Chris Smith

That's phenomenal, so are they saying then this could be the answer to Britain succeeding in the London 2012 Olympics or is there actually a sensible therapeutic point to this.

Interviewee - Matt Wilkinson

Well they do suggest that it could be used as a performance enhancing drug although it's utility wouldn't be that great because it would be quite easy to spot using most drug testing procedures, however, the major use for this would be that they could give it to people with heart failure and that could then help those tissues and organs around the body that were being starved off oxygen, get more oxygen and so that the damage done by heart attack would be much, much less.  

Interviewer - Chris Smith

And I presume also people with heart failure could benefit too because where there isn't the capacity in the heart in order to get the oxygen around the body in the same way, you just get more oxygen out of the blood, so the heart workload doesn't increase but much better oxygenation of the tissue.

Interviewee - Matt Wilkinson

Absolutely, yeah it would work in exactly the way you described so that it would just basically allow those tissues to survive for longer while somebody could come along and get the heart working again.

Interviewer - Chris Smith

Thank you Matt.  

(05:00 --   Molecular thermometer takes cell temperature)

Interviewer - Chris Smith

Well, lets talk about cells still but this time talking about turning up the heat on cells or at least measuring that heat.   Phil, tell us about this.

Interviewee - Phillip Broadwith

Yes Chris this is some research coming out of Japan which is taking a fluorescent polymer gel, injecting it into cells and measuring the fluorescence to tell the changes in temperature within the cell as it goes about its normal biological processes.  

Interviewer - Chris Smith

I mean, how on earth are they doing that?

Interviewee - Phillip Broadwith

This guy Seiichi Uchiyama in the University of Tokyo has invented a water-sensitive fluorescent molecule which he has built in to a polymer matrix and then turned that into a nanoscale gel.   The polymer has a very open structure at low temperature which allows water to get inside, that water quenches the fluorescence but when you increase the temperature, the polymer structure collapses which flushes out all of the water and increases the fluorescence.  

Interviewer - Chris Smith

So how do they see this actually being used and what does it tell to you?

Interviewee - Phillip Broadwith

There are two uses for it, eventually they want to be able to localize the gel on different areas of the cells to map temperature changes and relate those to biological processes but the other interesting thing is that diseased cells or pathogenic cells have a much high metabolic rate than healthy cells so you could use the difference in fluorescence as an indicator of disease and as a diagnostic tool.

Interviewer - Chris Smith

How do we know this real though? If you're injecting a foreign substance into a cell, which is capable of, telling the temperature of that cell, but it diffuses through the cell.   How do you know it is not actually affecting the behaviour of the cells or even insulating bits of the cells so they appear warmer than you might think they are normally?  

Interviewee - Phillip Broadwith

I am not too sure about the insulation effects of the gel but they have made very sure that the gel does not interact chemically with any of the elements present in a cell, so they've made, the polymer coating is chemically inert and then there is a layer of ionic sulphate groups on the outside which help it to be soluble and distribute around the cell.  

Interviewer - Chris Smith

People have tried to measure temperature with GFP in the past, haven't they, because GFP winks on and off the light at different frequency according to the temperature. So why is this better than that?  

Interviewee - Phillip Broadwith

GFP is a very large protein and also being a protein has the potential to interact with various other processes that are going on with the cell.   It can be fooled by changes in ionic strength and in pH.   This polymer is completely inert to all of those effects.   So it is only affected by temperature.

Interviewer - Chris Smith

Hot stuff, thanks Phil.  

(07:41 --   Steve Rimmer discusses creating smart wound treatments)

Interviewer - Chris Smith

And sticking with polymers to a new way now to protect wounds from infection.   Scientists have found a way to functionalize polymer chains so that they can grab bacteria and pluck them out of wounds.   Steve Rimmer.

Interviewee - Steve Rimmer

Basically, me and my colleague Linda Swanson from Sheffield University have been working on both the synthesis and properties of polymers that we call smart polymers or stimulus responsive polymers in water.   If we take some of these polymers and we make a particular architecture and that as we make a branched architecture and then we take fragments of antibiotics and attach them to all the ends of the chains, then when those antibiotics attach themselves to bacteria, the polymer changes.   It changes from, if you can imagine a sort of blanch piece of spaghetti that appears to collapse.   So this open system becomes a tighter collapsed coil if you like.

Interviewer - Chris Smith

And this presumably sequesters the bacteria inside the polymer at the same time.

Interviewee - Steve Rimmer

That's right well, what happens is you see when the polymers bind they go through this transition.   After the transition, the materials now have a very good surface - an adhesive for the bacteria if you like.   What happens then is that the bacteria actually start stick to each other, so the best way to picture this is the polymer acting like a glue and if the glue is a bad glue then the wound goes.  

Interviewer - Chris Smith

What's the polymer actually made of?

Interviewee - Steve Rimmer

That was a polymer called poly (N-isopropylacrylamide) which is a very well known material, I mean you know, it is being used in clinical applications before and it has this special property and that its water soluble but that's what we call a lower critical solution temperature and that means it comes out of solution as we increase the temperature.

Interviewer - Chris Smith

And are they safe in the human body?

Interviewee - Steve Rimmer

Yeah, they're pretty safe.   In general, most polymers they are safe.   There are a very, very few examples of clinical issues with polymer materials and in fact most of the issues normally with you know, monomers basically, giving toxicity, but we have a whole set of regulatory procedures to get through now and I guess you know with our industrial partners that's going to be probably the next stage.   What we still have done is we will have the polymers exposed to human cells in culture we don't see any toxicity issues.

Interviewer - Chris Smith

So why do you need to use antibiotics on the polymer to bait it, could you not just use any molecule that would stick to bacteria?

Interviewee - Steve Rimmer

Yeah, we can, we can, the reason we've used antibiotics so then I will in have to make the point that the antibiotics attached to the polymers they are no longer active as antibiotics.   So they don't kill the bacteria and we've no reasons to believe that there will be any issues with multiple acquired resistance for example.   There's wealth of data out there on the binding of antibiotics and potential antibiotics to bacteria.   So really that's where we start , so there was just a place where we knew cell molecules would bind to certain parts of different types of bacteria.  

Interviewer - Chris Smith

So when it comes to actually using this how does the polymer get applied? Is it in the form of the sheets that you can then put over a damaged piece of skin, could you use this internally within the body within for instance a bone graft, because bone infections are a major problem particularly in military context, how do we use it?

Interviewee - Steve Rimmer

Yeah, we can do both of those actually, so the stuff that we've actually prepared for publication in the moment concerns a soluble version of the polymer and so that in that case we would just apply a solution and you certainly could use it internally, you know, in a biofluid sensor and in that case the bacteria then goes through this transition as a solution but the only thing we've done recently is to attach it to a hydrogel membrane, so these are the materials very simple to contact lens materials and used quite extensively in wound dressings.   So that material we envisage is as being a type of wound dressing if you like, which could be applied as a sheet.

Interviewer - Chris Smith

And when the bacteria are sequestered by the material, what happens to them then and how do you get the material that has got the bacteria glued inside it back out?

Interviewee - Steve Rimmer

Yeah, okay it's a good point, so as far as we can ascertain the moment, the bacteria seem to stay viable.   We see a small decrease in viability and a few of them die.   So the figure is about 80% of bacteria remain active and alive.   In the terms of this membrane material this is relatively easier you can envisage a nurse for instance just applying the material in lot of standard wound dressing and then you know when it was infected basically, she would remove and replace it with another wound dressing, so little bit more difficult if you think of how we would get inside the body; if we add the polymers actually inside then that will be quite difficult to remove them.   With the open wounds though, my colleague, Sheila MacNeil is an expert in making solid models if you like, in vitro models of the in vivo situation and what she has done is that she has managed to make a skin model which she actually burns and then infects the bacteria and what we have been doing though is to take the soluble polymer, add it to the wound and then really the bacteria is just washed out essentially so that the polymer detaches them from the wound tissue and then, you know, just a saline wash would be sufficient as to wash them away.

Interviewer - Chris Smith

Steve Rimmer, he is based in Sheffield University and one other thing he told me is that he is also close to completing a system that will enable the polymers to also change colour when they pick up a bacterium which will give doctors an instant visual warning that a wound could be infected.

Jingle

Interviewer - Chris Smith

This is Chemistry World with me, Chris Smith and still to come a new way to combat high cholesterol, scientists have made a nano particle that works like HDL, good cholesterol and also how rain forests affect the composition and chemistry of the atmosphere.  

(14:12 --   New theory for nanotube growth)

Interviewer - Chris Smith

But first James, scientists have taken a fresh look about how carbon nanotubes grow.

Interviewee - James Mitchell Crow

Well that's right they have some insights based on a computational model of how carbon nanotubes might grow.   The interest behind this is that the nanotubes have all sorts of interesting properties from several electronic properties and that the fact and they will be strong and in order to make most of those properties and potentially fine tune them what scientists really wanted to be out to do is to control the way the nanotubes grow.

Interviewer - Chris Smith

And how would you do that?

Interviewee - James Mitchell Crow

Well in order to control how they grow, you really need to understand how they grow in the ways that they are made at the moment.   So what this team have done is they've modelled how the tubes grow and they don't roll by sheet of paper, they sort of grow along the length, they self assemble along the length of the nanotubes so carbon atoms get gradually added to the end of the tube.

Interviewer - Chris Smith

Is that done sort of ring by, ring by ring because if you look at these nanotubes, it's almost like layers of carbon atoms or is it done by adding individual atoms at a time?

Interviewee - James Mitchell Crow

It is atoms being added one at a time and these guys argue that effectively carbon strands sort of chains of carbons form from the ends of these nanotubes and they sort of wrap together and some multiple strands would be forming at the same time at the end of the nanotube and they wrap together effectively to sort of, zip this thing up.

Interviewer - Chris Smith

It's like hair plating.

Interviewee - James Mitchell Crow

Yeah, although they use f this analogy of that uses like almost weaving a rug.   They say that the more strands that is active on each tube than the quicker the tube grows that effects the chirality of the tube because the more strands that are growing sort of the more twisted the bonds are that are formed and experimentally it's known that chiral nanotubes are more numerous than the less chiral nanotubes so they say that that's evidence backs up their theory.

Interviewer - Chris Smith

How would you actually manipulate that or use that so that you could govern the number of threats that are growing wrapping around each other any given time and therefore the chirality and therefore the function of these nanotubes.

Interviewee - James Mitchell Crow

Well that's very much question for the future, understanding this process is the first step, but obviously if you could control the number of strands that form then it sounds like that would have quite a significant impact on the way that these things grow.

Interviewer - Chris Smith

And what sorts of things do people want to be able to do with these structures.

Interviewee - James Mitchell Crow

As I mentioned though these things have interesting electronic properties, they conduct in the same way that graphene does, but often when you produce carbon nanotubes you end up with a mixture of conducting and non-conducting tubes and it is very difficult separate them so if you are able to produce one or the other then you could either have a material that had nice insulation properties or have a material that had nice conducting properties and make the most of that.  

Interviewer - Chris Smith

Thank you very much James.  

(17:07 --   Combating high cholesterol using an HDL mimic)

Interviewer - Chris Smith

So now Matt turning now away from nanotubes but towards the body, potentially in cholesterol, high cholesterol if it is of the LDL variety it is a bad thing, scientists have now come up with a way potentially of tackling that by making high-density lipoproteins HDL, which is the good form of cholesterol, how are they doing it?

Interviewee - Matt Wilkinson

Well Chris what Chad Mirkin at Northwestern University has actually done is made a synthetic mimic of HDL and that molecule as you well know is the molecule that binds cholesterol and transports it to the liver so that it can be disposed.

Interviewer - Chris Smith

And how they have done that, how are they making these synthetic HDLs?

Interviewee - Matt Wilkinson

Well what they have done is they've taken a gold nanoparticle as the core of this molecule as the structure and then on to that they have added three different molecules one is apolipoprotein A-I and then they've taken two different phospholipids, one is a disulphide which binds very strongly to the gold nano particle and the other is phosphatidylcholine which is found in HDL itself.   So this structure itself is not really a drug, what it is, is a mimic of the actual structure of the high-density lipoprotein.

Interviewer - Chris Smith

And the idea of this would be that you could effectively artificially elevate someone's HDL which we know translates into protection from heart attacks.

Interviewee - Matt Wilkinson

Exactly yes, I mean, there's been lots and lots of interest in trying to make HDL raising compounds by the pharmaceutical industry.   LDL lowering drugs are well known, indeed the world's biggest selling drug Lipitor is an LDL-lowering drug and that is one of the stain families of drugs.   But so far there's has been a few attempts to make HDL raising drugs and unfortunately most of those have failed so far, I believe, there's one or two still going through clinical trials but everything is going quite on that front at the moment.

Interviewer - Chris Smith

So this could potentially be very promising, but would you use it on its own or the pharma industry suggesting that you could combine this with an LDL-lowering drug so that you get the best of both HDL up and LDL down.

Interviewee - Matt Wilkinson

Well Pfizer was looking at both lowering LDL cholesterol and increasing HDL cholesterol but unfortunately when the drug Torcetrapib failed a phase III clinical trial that seemed to put the kibosh on that whole idea but may be with actually using a synthetic mimic of HDL the future of the molecule look a bit brighter.

Interviewer - Chris Smith

Now research that has been done on these gold nanoparticles behaving as HDL is that actually into animals yet or rather they're still proving it in the dish.

Interviewee - Matt Wilkinson

I mean so far they've actually only proved this in the dish and what they've done is they've added this to a cell culture and shown that it does bind cholesterol.   One other things that they do say is that they actually rather than having created a drug they've created a drug lead that might help lead to actual therapeutics but I think the whole thing is that they've developed a new concept that does bind cholesterol very strongly.   One of the things that they will have to develop is that putting it into the body and making sure that it does not, you know, it does pickup the cholesterol but then also can be easily transported to the liver and that the cholesterol can be got rid of.

Interviewer - Chris Smith

Exciting news especially at a time when the drug pipeline is otherwise looking very empty, thank you Matt.  

(20:20 --   Nick Hewitt talks about atmospheric chemistry in the tropics)

Interviewer - Chris Smith

And now to the tropics where scientists have been trying to understand how rain forests influence the chemistry of the atmosphere.   It's an ambitious project called OP3 and Meera Senthilingam spoke with Nick Hewitt to find out what they've discovered so far.

Interviewee - Nick Hewitt

So OP3 is a very large consortium project it's called Oxidant and Particle photochemical processes above the south east Asian tropical rain forest which is a bit mouthful, so we abbreviated as OP3.   The aim of the project is to try and understand how tropical forests and the atmosphere interact together. The tropical forests emit certain compounds into the atmosphere. They take up compounds also chemicals from the atmosphere and in doing so, they mediate in the chemistry of the lower atmosphere, so we are trying to understand how tropical atmosphere and the biosphere interact together.

Interviewer - Meera Senthilingam

And how did you go about looking into this?

Interviewee - Nick Hewitt

Well this project is a mixture of field work and modeling activities. So the field work which took place in Malaysia last year was based at two grounds locations and also using an aircraft, research aircraft.

Interviewer - Meera Senthilingam

What did you actually measure?

Interviewee - Nick Hewitt

We threw everything at this. So we have measured practically every constituent of the atmosphere that is conceivable. We measured volatile organic compounds of which there are hundreds in the atmosphere.

Interviewer - Meera Senthilingam

And what are they?

Interviewee - Nick Hewitt

Well these are the compounds, basically hydrocarbons or partially oxidized hydrocarbons which are produced by plants by trees and emitted into the atmosphere, so these are the compounds that you can smell if you walk through a pine forest for example or if you smell flowers and you're smelling these reactive volatile organic compounds. The most important of them is isoprene which is a C-5 molecule. It contains carbon-to-carbon double bonds and it's highly reactive in the atmosphere and it takes part in reactions which leads to formation of ozone. Ozone in the lower atmosphere is a very important air pollutant. This is different to the ozone in the stratosphere where man's activities are removing the protective layer of ozone in the stratosphere which protects us from solar radiation. In the lower atmosphere ozone is harmful to human health. It reduces crop yield and is a very significant air pollutant. So we really need to understand how the atmosphere chemically works in the remote areas of the world, especially in the tropics because they contain most of the biosphere and so we need to understand, how the tropical atmosphere operates. Then we can begin to understand how air pollution and all the associated effects of man's activities are moderating that.  

Interviewer - Meera Senthilingam

So what have you found so far with your analysis?

Interviewee - Nick Hewitt

The site that we investigated in Malaysian Borneo is Bukit Atur.   It is in an undisturbed area of rain forests and we confirm that it is very clean. The atmosphere there is very clean. The oxides and nitrogen levels are very low, particles levels are low and ozone concentrations are low, so it is a very clean remote site, however, not too far away from this remote site, where the forest is been replaced by plantations, particularly oil palm plantations, man's activities there are influencing the composition of the atmosphere.

Interviewer - Meera Senthilingam

And how are they influencing the composition? What did you find in the plantation areas then?

Interviewee - Nick Hewitt

Well in the plantation areas, it's basically an agro industrialized landscape. So you are not only replacing natural trees or the natural rain forests with oil palm or palm oil trees but also all the associated agricultural and industrial activities in terms of trucks and people living there, burning fossil fuels for cooking, the processing plants where they process the palm oil and so this is introducing oxides of nitrogen into the atmosphere. Also very importantly is that these oil palm trees themselves emit huge quantities of reactive volatile organic compounds into the atmosphere, much more so is in the rain forests which they are placing.

Interviewer - Meera Senthilingam

So what this all mean then. Should we not be making so many plantation areas or should we be protecting our forests because they are actually taking away these compounds from our atmosphere as a whole.  

Interviewee - Nick Hewitt

Well, I don't think it means we should not plant plantations, it doesn't mean we shouldn't develop for example biofuels using oil palm as a biofuel. Now there's an important economic and environmental benefit to be done in that direction if we do it properly, what it does mean is we have to be careful about how that is managed and in particular how nitrogen is managed. Our results show that it is very important to minimize the emissions of oxides of nitrogen into the atmosphere in the tropical regions. Clearly it is very important to maintain the remaining areas of undisturbed tropical rain forests because they provide ecosystem services; they also act as lungs of the atmosphere. 

Interviewer - Meera Senthilingam

And so where are you going next with this project? What are you continuing to look into to understand this further? 

Interviewee - Nick Hewitt

Now we're analyzing with those data. We are running and developing models of the chemistry of the atmosphere. So we have another year or two of the predicted run and depending how our results span out, then we will look to see in which direction the follow up project should go.

Interviewer - Chris Smith

So we cut down the tropics at our parole. That was Lancaster University's Nick Hewitt talking to Meera Senthilingam about the OP3 project which is trying to understand the influence that rain forests have on the atmosphere. 

(26:13 --   Natural Ocean iron fertilisation)

Interviewer - Chris Smith

One thing that certainly has a major impact on the atmosphere is the ocean, mainly because it's a huge carbon sink. Green plants ut