August 2012

August

Chemistry World Podcast - August 2012

1:10 - Anti-social amino acids and the disease phenylketonuria

3:38 - Several papers claiming to break the 'oxo wall' have been retracted

7:34 - Andrew Harrison tells us about the neutron diffraction and spectroscopy experiments carried out at the ILL

14:54 - Recent Open Access policy changes from funders and government

20:58 - Robert West explains why smokers find it so hard to kick the habit - and how drugs can help

28:38 - Two different ways to make graphene - flattening nanotubes and building up hydrocarbons

32:15 - Printing 3D sugars to feed engineered organs

34:38 - Trivia: How are the Olympics like a ready meal?

(Promo)

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

(End Promo)

Interviewer - Meera Senthilingam

This month, printing sugars to engineer organs and amino acid causing changes in your brain, the rebuilding of the 'oxo wall' and success in the fight for open access publishing plus on the subject of battle, help is at  hand for those trying to kick the habit.

Interviewee -Robert West

If you are  average smoker in England tries to stop, 3% success rate and the other end of the spectrum, which is behavioural support plus using  one of the medications such as nicotine replacement therapy, you can boost that to 30%.

Interviewer - Meera Senthilingam

Robert West will be explaining the secret about success later in the program.  Hello, I'm Meera Senthilingam and with me for this August edition of the Chemistry World podcast, are Laura Howes, Philip Broadwith and Phil Robinson.

(Promo)

The Chemistry World podcast is brought to you by the Royal Society of Chemistry, look us up online at chemistry world dot org.

(End Promo)

(1:10- Anti-social amino acids and the disease phenylketonuria)

Interviewer - Meera Senthilingam

And we're kicking off this month with some antisocial behaviour, Laura.

Interviewee - Laura Howes

So I am going to be talking about some very antisocial amino acids specifically phenylalanine.  High levels of phenylalanine can cause a problem in  the genetic disease called phenylketonuria, you might see sometimes when you drink soft drinks, especially diet ones that it says it's a source of phenylalanine that's because people with phenylketonuria, when they get large amounts of this amino acid building up in can cause all sorts of problems in their brains for example and learning problems.

Interviewer - Meera Senthilingam

What effect has it been shown for this to have on the body?

Interviewee - Laura Howes

So, sufferers of phenylketonuria lack the enzymes that breaks down this amino acid to build up and then it goes into the blood and your sort of spinal fluid in your brain, it can cause organ damage, seizures and learning disabilities.

Interviewer - Meera Senthilingam

And so what's really been the finding here and who has been working on this?

Interviewee - Laura Howes

Okay, so this is work from a group led by Ehud Gazit at the Tel Aviv University in Israel and he was actually looking at what happens when there are large amounts of this amino acid together and they found a really interesting discovery.  If you think  back to things like Alzheimer's disease and Parkinson's those are associated with what we call fibrils , amyloid fibrils which are these sorts of clumps of proteins that form horrible things that stick in your brain and can cause problems.  What Gazit and colleagues have found is that you can actually get the same thing with just the one amino acid with this phenylalanine amino acid and it can form these fibrils on its own.

Interviewer - Meera Senthilingam

In the brain?

Interviewee - Laura Howes

Yeah, in the brain, in the spinal fluid.  They haven't actually I think looked at the brain, looked at sort of parts of the brain at the moment, this is just sort of looking at what happens when you get high concentrations of this amino acid and definitely this could lead to new treatments for the disease if you can work out what's causing it and potentially you can try and fight it

Interviewer - Meera Senthilingam

Have they mentioned what they'll be doing next with the finding?

Interviewee - Laura Howes

I think what they are trying to look out is to see whether other amino acids might do this, and seeing whether it could be involved in other amyloid diseases and obviously this has a lot of applications for not just phenylketonuria but things like Alzheimer's and Parkinson's disease which are associated with the same fibrils.  But I think it's just really, really interesting that these fibrils can grow when it's just a single amino acid rather than peptide which is what we thought before.

(3:38 - Several papers claiming to break the 'oxo wall' have been retracted)

Interviewer - Meera Senthilingam

And away from proteins to metals now and the bonds that  metals form, specifically the 'oxo wall' Phil and how something has actually been corrected here, or something has been proven to be wrong

Interviewee - Phil Robinson

That's right.  So you mention the Oxo wall there Meera and that refers to kind of root of chemistry, that governs the way in which metals bond to oxygen and we're talking specifically here about the transition metals, those are that metals that sort of sit in the middle of the period table, something is called the d-block as well.  So for members of that series, the early part of that series, as you progress across the periodic table, they form these terminal oxygen bonds very easily in contrast to bridging bonds, where you would have an oxygen atom on two metals and just creating a bridge between them, so this is just an oxygen atom bonded to a single metal atom.  For later members of the series, they don't form these bonds because of the electron density around the atom effectively, very simply as you progress along the period, you have more electrons around the centre of the metal atom and as the oxygen comes in, it wants to donate electrons into a bond with that metals, so the more electrons you have around the metal to begin with, the less likely that's going to have repulsion between two of these electrons.  So for later members in the series, you don't see these complexes being formed. 

Interviewer - Meera Senthilingam

And so what's really new here, so because this has been known for some time that this happens on either side of this wall.

Interviewee - Phil Robinson

Yeah absolutely.  This is a classic chemistry rule.  The 'oxo wall', but back in 2004, a chap called Craig Hill at Emory University in Atlanta in the US in collaboration with people around the world, actually they claimed they'd broken this rule, they'd broken the 'oxo wall' and they'd managed to create terminal oxygen bonds with platinum which is one of these late transition metals.  And he then went on in subsequent years to prove it  for a palladium, and gold, all members of this late transition series and all apparently breaking this fundamental rule of chemistry.

Interviewer - Meera Senthilingam

But unfortunately now, he's found that that wasn't actually correct.

Interviewee - Phil Robinson

That's right, that's right.  Craig admits himself that he was always sceptical about these results and the community at large was always very sceptical about this because it was such a well known longstanding rule, but as Craig says himself, he was among them, he was always a big sceptical about these results. So, over the years, even as they've been continuing to try do this, they've been analyzing their own results, and this year, they've come out with a paper that in fact says we were wrong, we didn't form those complexes and in fact the 'oxo wall' stands.

Interviewer - Meera Senthilingam

And what really happened to them to say this wasn't correct. So how did they manage to think they had the bonds before and now they suddenly see that they didn't?

Interviewee - Phil Robinson

Okay.  Well the precise ins and outs of it involves, it looks like, some quite heavy data crunching, they got huge amounts of data to support their evidence in the first place, but what they thought they had previously now on new analysis, where they thought they had platinum or gold, or palladium in the complex, as it turns out in most cases it was actually tungsten that was part of the ligands, the other ligands that were surrounding the metal, so in fact the 'oxo wall' rule was being adhered to all along.

Interviewer - Meera Senthilingam

And so what now, now they've seen that their earlier papers were in fact incorrect.

Interviewee - Phil Robinson

So as well as publishing this new paper, they've also taken a decision to retract all of the previous papers as well.  In the interest of science, so that people aren't misled or confused by them, and only allow the current paper to stand.

Interviewer - Meera Senthilingam

So it is taking us back almost in time to when the 'oxo wall' stood.

Interviewee - Phil Robinson

Exactly, exactly, erecting the 'oxo wall' once more.

(7:34 - Andrew Harrison tells us about the neutron diffraction and spectroscopy experiments carried out at the ILL)

Interviewer - Meera Senthilingam

Thank you Phil.  Now from the rebuilding of walls to the building of a large scale science facility, a neutron source, offering structural insights, no other institution can provide, using nothing more than a beam of neutrons.  Andrew Harrison is the Director of the Institut Laue-Langevin in France and explains why this sub atomic particle is so useful.

Interviewee - Andrew Harrison

Neutrons have a number of attributes that make them important.  First and foremost is the fact that the neutrons produced in our reactor have, although they're regarded as particles, they also have associated with them a wavelength and the wavelength of the neutron is reproduced.  It's comparable to the space in between atoms.  So just as x-rays are scattered by materials to tell you about the nuclear structure of those materials, so neutrons are scattered by materials, so in the centre is a complementary technique to x-rays. 

Interviewer - Meera Senthilingam

Yes,  people are used to using say x-rays to probe things, which perhaps are slightly cheaper and more widely available, but what does a neutron source offer, say that's better than an x-ray.

Interviewee - Andrew Harrison

The first is the fact that the strength of the scattering of a neutron by an element is not a very strong function of its mass.  You know the x-rays are scattered strongly or absorbed strongly by very heavy elements.  You see that in radiography, you know when you pass x-rays through a person for example, you see the bones picked out against the relatively less dense flesh and heavy objects as you know or heavy elements shield or block x-ray metals. Lead for example acts as a very good screen for x-rays.  By contrast, neutrons are scattered to a similar degree, not the same degree, but a similar degree by heavy and light elements and that means, you can determine the positions and learn quite all about the properties of light elements.  So, if you want to understand where the protons are in the material, whether it's in the biological system or whether it's in the material that's designed for hydrogen storage and then combination of hydrogen with other elements that make energy,  neutrons are an extremely good tool, pinning down precisely where those light elements are.  A second feature of the neutrons have is as neutral particles, they penetrate very deeply inside materials, so you could look at structure or part for example a complicated engineering component, many centimetres below the surface, in conditions where x-rays would simply be absorbed and wouldn't be able to penetrate.  Then there are two other features unique to neutrons, the first is neutrons have a small magnetic movement.  It behaves, if you like, like a little compass needle.  Therefore the way in which neutrons are scattered by materials also tells you about the magnetic structure of those materials and it's fair to say that neutrons tell us almost everything we know in detail about magnetic structure at the atomic level and that involves looking at fundamental properties of magnets, but also looking at where the structure of components of real functional magnetic materials such as the multi-layers you have in magnetic recording  media ,  all the materials  used in the magnetic recording head.  And in the final feature of neutrons that distinguishes it from x-rays is that the neutrons re-produce active moderation in the reactor are relatively low in energy and that means by measuring the changes in energy as they pass through a material, you can look at the excitations in the material, in other words, you can use neutrons to perform spectroscopy on materials.  And that gives us a very useful component to techniques that's infrared Raman spectroscopy. And again of course, you know, infrared Raman spectroscopic tools are much, much cheaper and much more abundant but because neutrons again have certain complexities, unique  properties compared to optical spectroscopy, they find themselves used in situations where they really only have to provide the appropriate tool and I'll give you one example.  If you want to look at the transformation molecule in a working catalyst, one of the things, tools you can use to do that is to follow, if you like, the vibrational fingerprint in the form, the vibrational spectrum of that molecule and that's often very difficult to do with optical spectroscopic techniques if the medium in which those molecules are supported is very opaque for that radiation.  Neutrons by contrast penetrate very effectively most materials.  So, you can actually image molecules in the middle of a porous catalyst or on the surface of a dirty working catalyst. 

Interviewer - Meera Senthilingam

And what's the source material  that you are using to create the neutrons in the first place

Interviewee - Andrew Harrison

So we, at the heart of a reactor is Uranium 235.  So it's a conventional fission reaction, not unlike that you'd find in a conventional power reactor. 

Interviewer - Meera Senthilingam

And I guess, as is the case with x-rays and x-ray diffraction as well, is there possibilities and the types of say, materials analyzed, is that quite diverse and so is it a quite a versatile technology?

Interviewee - Andrew Harrison

Absolutely.  I mean, so we support work from about 2000 scientists across Europe every year and they bring materials in every area of science.  So, again we support chemical crystallographers, we support polymer chemists, we support people who look at biological membranes and biological macromolecules, engineers, people who're developing alloys for containment in nuclear fusion, every field, where you need to know the structure of the material or the magnetic structure of the material or the vibrational character, particularly solids, is amenable to neutron scattering.

Interviewer - Meera Senthilingam

And could you give an example, say of something that has been looked at more recently at the facility, and a finding perhaps that's resulted from it?

Interviewee - Andrew Harrison

Yes, for example at the moment, we have several groups of scientists who wanted to develop better polymer electrolytes for use in fuel cells and the function of a polymer electrolyte among other things relates to the ability of water and charged species to move through membrane as the battery is discharging.  Some of the experiments that we are performing actually allow you to look at the dynamics of molecular transport in a real polymer electrolyte in working battery as the chemical reaction proceeds.  And again the beauty of the technique is because neutrons are penetrating you can look at precise region of the material in a working environment.

Interviewer - Meera Senthilingam

And I guess, as you touch on that, the aim is to see these kinds of dynamic structure in order to understand more and therefore advance these things further so to develop better fuel cells and so on. 

Interviewee - Andrew Harrison

Absolutely.  And I think one thing that's changed is, you know, 20-30-40 years ago, a facility such as ours or a facility that supported x-ray diffraction were more about looking at static structures, you know, looking at, trying to understand a lump of material in a particular state.  Increasingly, as sources get bright and as techniques develop, we can look at the evolutionary structure, we can look at systems, the work phrase for them is in operando, in a real working dynamic system, looking at the evolution of structure throughout a chemical or material processed.

(14:54 - Recent Open Access policy changes from funders and government)

Interviewer - Meera Senthilingam

Andrew Harrison.  Now what would you do to make science available to all, enabling a world where everyone can access whichever scientific information or papers they wish with ease.  It seems what it takes to achieve such a feat is some politicians, policy makers and a large influential funding body, Philip.

Interviewee - Phillip Broadwidth 

Yes Meera, the debate about open access publishing has been going on for quite a long time, but there's been quite a few developments in the last month that has really brought it to the fore, in terms of political and scientific discussion.

Interviewer - Meera Senthilingam

Well let's take a step back first of all and just discuss the whole concept of open access.

Interviewee - Phillip Broadwidth 

Okay Meera, well what open access basically means is that research findings that generally have been paid for by public funds should be available to anybody who wants to read them.  That sounds like a kind of obvious thing, but most journals charge a subscription fee to read the research.  Now if you don't want to do that, there are various ways of getting around it.  One option which is called green open access is for researchers to publish their research in the normal way in journals that charge a subscription but after a certain time generally between six months and a year they would then deposit the paper in a central repository or one that is run by their University which would then make it available on line on the web in its entirety to anyone who wants to read it.  The other option which is what's called gold open access is that a fee is paid to the publisher , whether that comes directly from the researcher or from their funder or whatever it is something that needs to be worked out, but the fees paid on publication and the publisher themselves makes the article available for free on the internet through their own web site.

Interviewer - Meera Senthilingam

And so what's happened more recently in this area because this is a longstanding debate?

Interviewee - Phillip Broadwidth 

Okay well at the end of last year, David Willetts, the Minister for Universities and Science commissioned Dame Janet Finch and a working group to examine the different possibilities for open access to UK research.  They put out their report last month and the general finding was that yes, the UK researchers should pursue open access publishing.  They should make their research available and the most sustainable route to do that from the point of view of both publishers, researchers and the funders would be to follow the gold open access model.

Interviewer - Meera Senthilingam

But I guess with such changes and recommendations there is going to be some kind of field cost associated with this.

Interviewee - Phillip Broadwidth 

Oh yes Meera, and that comes in kind of two aspects.  There is a quite a big cultural shift to go from the kind of status quo of publishing to a more open access mindset and that shift is happening a lot more in the biomedical sciences and physics to an certain extent but not so much in chemistry.  So there will need to be a more cultural shift in the chemistry community but there's also a financial burden and  the Finch Report estimates that the total cost to the UK higher education as a whole could be in the region of 50 to 60 million pounds a year, certainly not a small thing but there are potential mechanisms in place to find that money from somewhere.

Interviewer - Meera Senthilingam

And so Phil and the Wellcome Trust have also been getting involved in this area in this debate recently?

Interviewee - Phil Robinson 

That's right, that's right. So the Wellcome Trust are one the UK's biggest funders of research and in fact they have supported open access publishing for some time.  They actually have a policy, anyone who is funded by the Wellcome Trust, the research that they do has to be made available within six months after it has been published. But now the Wellcome Trust are kind of cracking down or they're tightening up this rule because while they apply this rule to anyone who is funded by them it's not often abided by.  So in fact almost half the research that is funded is not ultimately available.  , In fact , so, what the Wellcome Trust has now said is that for anyone who is feeling to do this, you're going to be penalized and they'll have portion of their grant withheld and also in the future people submitting grants to the Wellcome Trust, any publications that they have are not in open access journals will not be considered as part of the grant application

Interviewer - Meera Senthilingam

When are they planning on enforcing this?

Interviewee - Phillip Broadwidth 

Well, with immediate effect. So this starts with papers published in 2009, so if you get it before that then you seem to have got off the hook, but from 2009 onwards all papers  that still are behind pay walls they will need to survive otherwise you won't get your money.

Interviewer - Meera Senthilingam

And so this really should help, most journals are going to go this way. 

Interviewee - Phillip Broadwidth 

It's another incentive yeah, exactly, exactly to push the open access model.

Interviewer - Meera Senthilingam

And what about moving outside of the UK into Europe Laura?

Interviewee - Laura Howes

Yeah.  So, not only is the Wellcome Trust enforcing its open access rules, but we've had news from Europe that actually the European Commission is planning to make all of its research that has got its funding through a program called Horizon 2020, that part is 80 billion Euros worth of research and it would like all of its research that it funds through that program also be put through either gold or green open access.  They don't specify which,.  they leave it up to the researcher and presumably at the moment they say that they haven't got a massive pot of money funding the gold open access that Philip was talking about, but certainly that's another push for researchers and for publishers, which possibly would have happened anyway but may be it needed a kick and this may be it.

Jingle

Interviewer - Meera Senthilingam

You're listening to the Chemistry World podcast with me Meera Senthilingam.  Still to come, we're piecing the puzzle together to create new forms of graphene and printing out sugars to build artificial organs, but first a helping hand for the millions of smokers trying to kick the habit.  Smoking causes 5 million deaths globally each year from smoking related diseases, but despite many smokers wanting to quit, over 70% of those that try fail to fight their addiction.  Robert West from University College, London explains why.

(20:58 - Robert West explains why smokers find it so hard to kick the habit - and how drugs can help)

Interviewee - Robert West

One can use the term nicotine addiction, but it's a bit of an over simplification.  Ultimately if the cigarettes didn't have nicotine in them, no one would smoke them, but just like with any kind of drug or even behaviour addiction there's more to it than that, nicotine acts in many different ways in the brain to keep people smoking.  One of them is that after repeated ingestion of nicotine there's an alteration across the brain chemistry which means that if the nicotine levels become depleted like overnight for example or when you're trying to stop smoking, smokers experience what you might call a nicotine hunger, it's an quite drive, very like hunger for food so if you don't smoke, just think about yourself being very, very hungry for food, that then create obviously what can seem to the person, quite an overpowering urge to smoke, that's one thing.  The second thing is that nicotine forms links in the brain between the situations in which you smoke and the act of smoking.  So even the smokers who don't necessarily smoke every day, if they smoke in particular situations, they experience an impulse to smoke in those situations, it feels like a behavioural addiction, but actually it's completely attributable to the fact that nicotine causes release of  dopamine in the part of the brain that does this link forming.  And then the third factor is that being humans, we form beliefs about things and what happens when people don't smoke for a while, they start to experience withdrawal symptoms and one of them is irritability and other one is depression and anxiety and then they smoke a cigarette and you get that feeling of relief.  The smoker interprets that feeling as relief from stress and they come to the belief that smoking helps the stress, it doesn't help the stress, it helps with the stress caused by not smoking because you're nicotine addicted.  But that belief means that even months or years after you've stopped smoking, you encounter a stressful situation, your brain is thinking, aha what shall I do, I'll smoke a cigarette and that causes a lot of relapse.

Interviewer - Meera Senthilingam

Many say, ways that perhaps people know of trying to quit are perhaps some of the over-the-counter type options, so thinks like gums, and fake cigarettes and kind of metal cigarettes, but these are traditionally thought to not have a very high success rate.

Interviewee - Robert West

The problem is that nothing has a very high success rate.  If your average smoker in England tries to stop, let's take a hundred of them, by the time the year is out, 97 of them will be back to smoking, if they try and do it without support or help.  So that's the 3% success rate and vast majority of those will go back to smoking within the first week.  Say, the other end of the spectrum with the very best support that medical science and psychology can provide, which is going to see a specialist who knows what they're doing to give you behavioural support plus using one of the medication such as Chantix, or nicotine replacement therapy, you can boost that one year outcome to 30% rise, that still means that 70% are going to fail even with the very best that we can do, but the difference between 3% and 30% is a hell of a lot of lives saved.

Interviewer - Meera Senthilingam

Going down, the pharmaceutical route, what are the, say benefits of this work, does this actually do to the body to have such an improved success rate?

Interviewee - Robert West

Let's start with the nicotine replacement products, you know, they do what they say on the tin, they replace nicotine.  Now lot of people think well that doesn't make any sense, it's like giving alcohol to an alcoholic, but that's a misunderstanding of  the way that nicotine works.  Nicotine from a cigarette is delivered very rapidly through the pulmonary circulation to the brain and it's that bolus, that sharp intake of nicotine which is so addictive, you can think of it like crack, cocaine versus chewing cocoa leaves.  None of the nicotine products that you've got so far can mimic that or attempt to mimic that.  The long and short of it is that if you can simulate a cigarette in terms of pure nicotine delivery, then you can do a lot to overcome the cravings and the urges and so on and to the extent that your nicotine delivery system is delivering the nicotine more slowly than a cigarette, people will find it relatively easy to come of those nicotine products.  The other main drug is Varenicline known as Chantix and this was developed specifically as a nicotinic partial agonist which binds to the receptors that are believed to be particularly relevant to nicotine addiction and this particular drug is demonstrably more effective than say a single form of nicotine replacement like a patch, demonstrating more effect than its main competitor, which is drug called Zyban and it does get good success rates.  It reduces the cravings by giving you a certainly level of activity in the neural pathways concerned, but only up to a point, and that means that it is not in itself satisfying or positively reinforcing or rewarding, so you don't get dependent on it.  But it's also binding very tightly and very efficiently to the receptors that nicotine would normally be on and that blocks the nicotine from getting on those receptors.  So if you do have a lapse and you have a cigarette, then there's no way for the nicotine to go in the brain and so it's not so satisfying so it's less likely to lead to full relapse.

Interviewer - Meera Senthilingam

So, how successful say, has this been and would you say therefore, that this type of drug is the way forward in treating addiction?

Interviewee - Robert West

I think it's part of the way forward.  I think there are a number of issues that always comes up.  If a majority of smokers want to use this drug to help them stop, we would see smoking prevalence plummet because they would succeed. So in that sens