Chemistry World Podcast - July 2007
(Promo)
Brought to you by the Royal Society of Chemistry: The Chemistry World Podcast.
(End Promo)
Interviewer - Chris Smith
Hello, this is Chemistry World Podcast No. 10 with me Chris Smith and with the Chemistry World team Mark Peplow, Bea Perks, Richard Van Noorden, James Mitchell Crow, and Victoria Gill. In this month's edition of the program, there's a new kid on the antismoking block, but how does it work.
Interviewee - Robert West
It's what is known as a partial agonist. So, it doesn't have the same full effect that nicotine does, but what it does have is enough of an effect to reduce the withdrawal symptoms and the craving. So, if you do have a cigarette then it is not so satisfying or rewarding, so you are less likely to get back to smoking.
Interviewer - Chris Smith
Robert West with guidance on the best ways to quit and he is coming up in just a moment. Also biochemical credence for the Atkins diet.
Interviewee - Victoria Gill
A team at the University of Southwestern seem to have found the hormone that is responsible for the fat burning that happens during the Atkins diet. If you subject mice to a ketogenic diet, basically an Atkins diet very high in fat, high in protein, but very low in carbohydrates, you see a high production of FGF-21.
Interviewer - Chris Smith
And researchers discover why you can still feel pain even when your hands go numb with the cold.
Interviewee - Richard Van Noorden
And when they put these mice on blocks of ice, they couldn't feel a thing, they just stood calmly on the ice and you know they would have frozen solid.
Interviewer - Chris Smith
Ouch, mind you, a mutation in that gene would probably come in very handy on a cold day, rather like we are having this summer. Well, that's all coming up along with this month's Chemical Conundrum. We wanted to find out why orange juice tastes so disgusting after you have just cleaned your teeth. Don't believe me, well go and give it a try, but before you do that great news for the aerospace industry and even for my wife, who is fond of denting our car, because researchers have come to the rescue. Bea what have they done?
Interviewee - Bea Perks
I have got polymers that can heal themselves and heal themselves over and over again, which is a real first.
Interviewer - Chris Smith
How do they work?
Interviewee - Bea Perks
Well, first of all, this is Nancy Sottos' team at the University of Illinois in the States and she has used a direct-write technique to create an epoxy resin base that's infused with the network of horizontal and vertical channels 200 micrometer, something a bit like capillaries you might find in the blood system, but rather than having blood in them, they have a healing agent, very-low viscosity, monomeric dicyclopentadiene. On top of that vascularised layer, they put a solid epoxy resin layer, into which is incorporated a catalyst called Grubbs' catalyst, one of the catalysts that Robert Grubbs managed to win the 2005 chemistry Nobel prize for developing. So, what happens is when the polymer is injured by a crack that forms at the very top of the surface and goes down through the epoxy resin layer with the Grubbs' catalyst and it gets down to the bottom, where there's this almost, sort of, blood supply of healing agent and by capillary action was drawn up through the layer with the catalyst in it. So, when it meets the catalyst, it polymerizes and heals the wound.
Interviewer - Chris Smith
But, surely you said you could do it again and again, again, but surely it's restricted to actually how much of the healing agent is there or is there some kind of endless reservoir?
Interviewee - Bea Perks
Presumably, it's relatively endless. The reason that the other ones did not last forever and ever was because the catalyst was in capsules in that epoxy resin layer. So, while using capsules, of course, you only could use a very limited amount of catalyst, but this is all the way through the epoxy resin. So, you are not going to run out of it.
Interviewer - Chris Smith
Does it heal cleanly? Is it a sort of scar-free heal or do you end up with a mark?
Interviewee - Bea Perks
Well, I have to say the pictures they have in the paper there are marks, but I mean that is so heavily magnified that I think to the naked eye it would be pretty smoothly mended.
Interviewer - Chris Smith
And where would you see this being applied, where do they suggest this should be deployed?
Interviewee - Bea Perks
Well, we spoke to Ian Bond at the Aerospace Composites Research Group in University of Bristol, who is very excited about it, because in aerospace we don't want to have things that might get injured up in space if they mend themselves, hurrah!
Interviewer - Chris Smith
Pretty harsh conditions in space then?
Interviewee - Bea Perks
Well then, now that's the next thing. So, this paper was published in Nature Materials. The same team published in the Royal Society's journal Interface, a very similar system, but they used a different catalyst, because the Grubbs' catalyst apparently is expensive and it has limited temperature stability and could not use those temperatures they are going to be facing in the aerospace industry.
Interviewer - Chris Smith
Well, I guess we just have to watch this space with that one, but certainly sounds intriguing and sticking with this sort of science in the very small and ultra structures people are blowing nano bubbles James, what's this all about?
Interviewee - James Mitchell Crow
That's right. Scientists in Harvard have found a much improved way to incorporate nanoparticles into polymer films. What they have done is, taken a liquid mixture of the polymer and the nanoparticles and they have effectively blown a bubble of it. It's a process called blown film extrusion. It's the technique that's used to make things like beanbags, so not terribly expensive thing to do.
Interviewer - Chris Smith
So, you just got a giant bubble of polymer with the particles embedded in it, but do they therefore form organized structures in the bubble or are they all over the place?
Interviewee - James Mitchell Crow
No they are actually very well aligned.
Interviewer - Chris Smith
But why?
Interviewee - James Mitchell Crow
Well, that's a question that Charles Lieber, who has led the research hasn't yet worked out, although he told Chemistry World he was very excited that they did line up and not only do they all line up, but they are all distributed very evenly throughout the film, whereas other techniques to incorporate nanoparticles into polymer films have tended to end up with clumps.
Interviewer - Chris Smith
How big are these bubbles, James?
Interviewee - James Mitchell Crow
Well, the biggest they have made so far are about 20 x 30 cm, but the Harvard team thinks that there should be no problem with making these composites on meter scale.
Interviewer - Chris Smith
So, what you would do is make a giant bubble and then chop it up into small bubbles or small pieces that you can then use?
Interviewee - James Mitchell Crow
Exactly, and you can make flexible pieces or pieces that have natural curve to them.
Interviewer - Chris Smith
And it works with any material, you should be able to get any kind of species in nanoparticle and it will accommodate those?
Interviewee - James Mitchell Crow
Exactly, the team have shown that you can use nanowires and carbon nanotubes, so you could use these as sensors and the fact that all the wires are lined up means that they should be able to be incorporated into some sort of circuitry as a detector for gases or potentially even chemical warfare agents, and using the carbon nanotubes, these could be used for very strong coatings, say, for example, you might paint them onto airplane wings, for example, and if you could get enough of the nanochips into the polymer then you could end up with a material that is even stronger than Kevlar.
Interviewer - Chris Smith
Thanks James, and now to something else that's even tougher than Kevlar, that's giving up cigarettes, now that smoking is banned across Britain, at least in public, there has never been a better time to bite the bullet and give up. So, I asked UCL's Robert West, how worshippers of the weed should go about it?
Interviewee - Robert West
Percentage of people smoking is about 28% in the UK adult population and all of those if you ask random samples any one time, you find that about 70% will say yes they would like to stop smoking and you find that about 50% will have made at least one quit attempt in the last year.
Interviewer - Chris Smith
James Bond said 'giving up smoking is easy, I have done it hundreds of time', so, why have your 75% of the people wanting to quit and hardly any of them succeeding?
Interviewee - Robert West
Well, you know, we use the term addiction, but essentially it does come down to nicotine, but it's a bit more complicated than people think. The way that nicotine works is not in the, sort of, classic way that people think of drug addiction, in other words, that you have to have that particular nicotine level in the brain in order to be able to function normally. Nicotine actually operates in some more complex way to make the cigarette itself addictive by a process of association.
Interviewer - Chris Smith
So, how do we actually get people off them, because is it just a case of supplementing the nicotine, if it were that easy you would think that people would be able to stop smoking, but that does not seem to work?
Interviewee - Robert West
Now, first of all, one has to realize that you are talking about a behaviour and any sort of behaviour pattern is going to have a whole range of factor that contribute to it and essentially the way that we go about it is to look at both the psychological side as well as the pharmacological side and essentially what you are doing with the psychological side is you are bolstering the motivation to stop and what you can do is to use a whole range of trick, group pressure, empathy, all kinds of things to just add enough motivational force to keep them from having that cigarette. What we do on the pharmacological side is reduce the motivation to smoke and there are number of ways of doing that, obviously there is the nicotine replacement therapy, nicotine patch, gum, inhaler, lozenge, nasal spray, etc. There's Zyban otherwise known as bupropion, which is a stimulant drug also used as an antidepressant and then there's a new medication called Champix or varenicline,, which works by binding with very high affinity to the particular kinds of nicotinic receptor subtype with what are known as alpha-4 beta-2 subunits, then, which lie at the heart of nicotine addiction so that nicotine cannot get on there and is what is known as a partial agonist. So, it doesn't have the same full effect that nicotine does, but what it does have is enough of an effect to reduce the withdrawal symptoms and the craving. So, you do have a cigarette then it's not so satisfying or rewarding so, you are less likely to go back to smoking in full force.
Interviewer - Chris Smith
So, if you look at all of these different interventions, how successful is each of them, if you, sort of, rank them, what's the best thing to try and do to get off?
Interviewee - Robert West
I would say if you don't know anything about the smoker, about what the history is apart from the fact that there was smoker and assuming they are not contraindicated for I would go for Champix plus professional behavioural support of the kind that is available in the NHS stop smoking service.
Interviewer - Chris Smith
How many people if you would subject to them that would you expect on a good day will successfully give up?
Interviewee - Robert West
About 20-25% would be completely smoke-free for a year, of whom we would expect about 30-40% to relapse at some point later on.
Interviewer - Chris Smith
What happens if someone just did get a try of the chewing gum, how well would they do?
Interviewee - Robert West
They would probably do somewhere between 15 and 20% something like that with behavioural support as well. With the medications on their own, then the success rates are somewhat lower, because you are just dealing with obviously one side of the equation.
Interviewer - Chris Smith
And when July 1st kicks in, what sort of impact this is going to have on people's motivation, will this help?
Interviewee - Robert West
Yes, it does. People do try to give up in anticipation. They also try to give up on the day, but experience from Ireland has indicated that actually more people tried to stop once the sort of reality that it has become a bit more difficult to smoke kicks in. The problem that they found in Ireland and in Scotland is that people won't use effective treatments most will relapse. The government has estimated that in England it might cause maybe 600,000 people stop smoking, but I would be amazed if it's more than about 100 to 200 thousand, which is still, you know, a lot of people, lot of lives saved, but it is nothing like this, sort of, impact that one would hope.
Interviewer - Chris Smith
UCL's Robert West explaining how to do what even James Bond wasn't capable of, give up smoking.
(Music)
Interviewer - Chris Smith
Coming up, we will be continuing our lifestyle theme to this month's Chemistry World Podcast with a look at how to make your skin look younger, but first, how about losing some weight too, well, if you are tempted by the Atkins regime, then new research suggests that you may well be on solid biochemical ground, what's this all about, Victoria.
Interviewee - Victoria Gill
A team at the University of Southwestern seemed to have found the hormone that's responsible for the fat burning that happens during the Atkins diet.
Interviewer - Chris Smith
So, it's not just a lot of rubbish, there is actually credence given to what Atkins suggested in terms of eating a high-fat diet and losing weight?
Interviewee - Victoria Gill
There seems to be biochemical credence to Atkins after all. It is actually a dual publication of two studies that backup this factor. So, a group led by Steven Kliewer at University of Southwestern in the US and he was studying some receptors called PPAR? in liver that's connected to metabolism and he found that they were stimulated by this particular growth factor, a hormone called fibroblast growth factor 21, FGF-21.
Interviewer - Chris Smith
But what was the connection between that and Atkins diet then?
Interviewee - Victoria Gill
Well, because he had found that these particular receptor was stimulated by this hormone, he decided to look at the hormone and what he found was that the hormone stimulated fat metabolism in the liver and at the same time a group at the University of Boston found that if you subject mice to a ketogenic diet basically an Atkins diet, very high in fat, high in protein, but very low in carbohydrates, you see a high production of this FGF-21.
Interviewer - Chris Smith
And if you give this to normal mice, does it then fool them into thinking they are on the Atkins diet and therefore they lose weight?
Interviewee - Victoria Gill
That's exactly what Steven Kliewer's group did. They used transgenic mice that produced lot of FGF-21 and direct injections of FGF-21 and despite the fact that the mice were on a normal diet, they looked like they were starving, they were burning a lot of fat. What they do is when a person is starving and when he has very few carbohydrates to burn, which is a normal energy source, a food source, he will start to burn lipids or fat stores. This is why the diet is called ketogenic, because you will produce ketones, which are a different type of fuel for your tissues.
Interviewer - Chris Smith
Have they looked in humans to see if the same effect is triggered, that must be the critical thing?
Interviewee - Victoria Gill
Not yet, no. This is early days, early studies in mice. This is something that they will take forward into obesity research, but in actual fact, Steven Kliewer's next step is to look at the link between FGF-21 and aging. He is very interested in the link between calorie-restriction diet and longevity. There have been a lot of previous studies that have shown that animals on a calorie-restricted diet live longer, and a few scientists that I spoke to there, were involved in that research are now wondering, it could be Atkins diet actually make you live longer. There is actually an active group in the UK, who are undergoing their own personal experiment to stay on a calorie-restricted diet to see if they live longer, I mean, it's impossible to prove, but it's interesting.
Interviewer - Chris Smith
I spoke with some of those people and they said, you may not live longer through calorie restriction, but you are so miserable that life seems to last twice as long, and Richard, there's a very interesting piece of work, which has been done on, why it is that you can still feel the cold despite having completely numb hands and feet?
Interviewee - Richard Van Noorden
We all know the sting of winter air and the real agony of moving our frozen fingers and now scientists have discovered exactly why extreme cold does hurt. They have even managed to create mice who can stand on blocks of ice without feeling any pain. Now, it might be a surprise that we should feel pain in the cold, because as Katharina Zimmermann at the Erlangen University explains me and she led this research. We feel pain when protein channels let sodium ions flow across the membranes of neurons and that fires off electrical nerve impulses.
Interviewer - Chris Smith
So, in the cold, you would expect them to work more slowly and therefore the nerves would signal more slowly and less effectively and so, you should, in the same way as you go numb, feel less pain?
Interviewee - Richard Van Noorden
Exactly. It turns out that there are different types of sodium channels doing this job; one Nav1.7 fires very fast, very low threshold; another Nav1.8 fires more slowly, threshold is much higher, but what Zimmermann and her colleagues found was that as the temperature went down, Nav1.7 got much slower and it got sensitized with the cold and nothing seemed to be happening, but Nav1.8 really came into its own. It was really responsible for feeling the pain at very extreme cold temperatures.
Interviewer - Chris Smith
So, does this suggest it's a sort of evolutionary protector; it's there so that it does remain active in the cold and warns us, hey, you might be in danger of getting frostbite in this part of your body?
Interviewee - Richard Van Noorden
Yeah, it seems to be a primitive ion channel and everyone is really quite sure what it was there for and now that is the first clue we have got. Now, what's interesting is that the team, teamed up with John Woods at University of London in UK and he helped them create mice, which didn't have this Nav1.8 ion channel at all, and when they put these mice on blocks of ice, they couldn't feel a thing. They just stood calmly on the ice and you know, they would have frozen solid.
Interviewer - Chris Smith
So, this suggest it may be actually beneficial for humans, because there are some human clinical conditions where cold triggers extreme pain state. So, identifying this receptor or this particular channel could be very useful in helping to treat those people then?
Interviewee - Richard Van Noorden
Yes, you are talking about allodynia, which is when people suffer from bites and pains even when temperatures are normal. Now, it has actually been a real challenge to find drugs that act against Nav1.8, because it's actually so similar to Nav1.7, but in May this year, US companies, Abbott and Icagen did announce a potent drug which blocks the ion channel in rats, which is really quite an achievement and it's thought that maybe that might help people who suffer from cold allodynia.
Interviewer - Chris Smith
Now, there is a research you can warm to, thanks Richard. To China now, last month we heard from Mark Peplow on how China is rapidly becoming a chemical powerhouse, particularly in the area of the hunt for cleaner fuels and the second of his dispatches from China, Mark finds out how universities were increasingly opening up to international collaboration.
Interviewer - Mark Peplow
Chemistry is booming in China. The enormous investment in science and technology here along with a real conviction that science and development go hand in hand has made the subject enormously popular with undergraduate students. To find out more about the state of academic chemistry in China, I went to the Beijing University of Chemical Technology to meet Professor David Evans. David started his academic career in the UK, but in 1996, he started to collaborate with professor Duan, here in Beijing. I asked him what convinced him to move out here for good.
Interviewee - David Evans
Although at that time in 1996, the conditions were bustling here at UK or elsewhere in the west, then I could see that that was real potential for development and I thought well if I didn't take this chance I am going to regret it in 10 years' time, and here I am 10 years later.
Interviewer - Mark Peplow
Now, one of the things about this department, I understand this is the fact that there is a real emphasis on applied science here, can you tell me a little bit more about that?
Interviewee - David Evans
Yes, there's a very strong principle about that and other labs in the university that will focus not just on pure research, but always under pinning the fundamental research, there is a real actual application of the materials. With in our own lab we are not just doing lab scale synthesis, we've been identifying promising material, we actually have a pilot plant where we can actually do the initial scale up in half and this makes it very much more efficient, very much quicker, to actually implement full scale production if the pilot plant trials are success.
Interviewer - Mark Peplow
And you have actually had some successes in transferring stuff from the lab to actual full scale production?
Interviewee - David Evans
Yes, we now actually have three different types of materials being produced commercially that they used as additives in agricultural plastic foams, the green houses to keep the temperature high in that, they are used as environmentally friendly in electric cable insulation, for example, and other areas and they are also used as thermo stabilizers for PVC.
Interviewer - Mark Peplow
Now, in order to commercialize these sort of things that the university can work with governments as well, so it actually gets the sources of funds there are?
Interviewee - David Evans
Yes, in many cases they are very joined up. For example, in one of the production plants we have in the northeast of China, the factory we collaborated with have got individual development grant from one scheme under the government and in addition to that this plant is able to borrow money from the banks, which it would not have been able to do otherwise and then, the Beijing University putting the technology, then we have now set up the production line producing the material.
Interviewer - Mark Peplow
Now, as you said before, you have been working here for more than 10 years, when you first arrived, how unusual was it for a westerner to be working in a Chinese university?
Interviewee - David Evans
Doing science, there were very, very few and they still are. In the past, most Chinese students who went abroad to do PhDs or postdocs didn't come back. They have not seen the facilities here. In many cases, there are atleast scores of opportunities are perhaps more because the things are growing so quickly, so that certainly now some overseas Chinese are coming back and I am sure that in the future there will be more westerners like me to make China the place to build a career on their own there.
Interviewer - Mark Peplow
So, what's the effect been there on the science and technology in China of the last 10 years of this policy of openness and expansion and increasing international contact?
Interviewee - David Evans
There has been an enormous expansion in funding, both in terms of applied research and also basic research, certainly now the labs we have here are comparable to what we would found in most labs in the UK or most labs in the west. I think when I came we could describe what we had was out of the art, whereas now it is much closer to state of the art.
Interviewer - Mark Peplow
So, it is pretty clear that China is very quickly becoming a force to be reckoned with in cutting edge chemistry, but I think the real sign that China has reached big time will only come when people like David Evans are no longer considered unusual for having made their homes and careers here and as the research base grows stronger it seems almost inevitable that more and more scientists will want to follow him here.
Interviewer - Chris Smith
Chemistry World's editor, Mark Peplow, and you can find out more about chemistry in China when Chemistry World launches its Chinese edition in September. You will be able to find that online at www dot chemistry world China dot org. From that high note to a sad story now and why things are not looking too good for some players in the pharmaceutical sector, Victoria.
Interviewee - Victoria Gill
Well, one drug company in particular GlaxoSmithKline, their very widely prescribed diabetes drug, Avandia has come in for some pretty severe criticism from a meta-analysis that was conducted by Steven Nissen at Cleveland Clinic in Ohio in the US. He is a pretty influential figure. He is the man now famous for conducting the meta-analysis that highlighted the problem with Vioxx Merck's anti-inflammatory treatment for arthritis, which has now been withdrawn and there are lot of lawsuits pending on the back of risks associated with that drug. He has done a similar thing with Avandia. He noticed a problematic pattern with cardiovascular risks in clinical trials that have been published by GSK and so he conducted a meta-analysis with all of the clinical data that was available and concluded that indeed there was an increased risk of heart attack and death from heart attack.
Interviewer - Chris Smith
That's a real blow, because when this family of drugs, these glitazones drugs came out everyone championed them saying they can really transform the therapy of things like diabetes which they are prescribed for. So, what's going to be the spin-off, what's the implication of this finding?
Interviewee - Victoria Gill
You are quite right, they work by a different mechanism to other widely prescribed drugs so that they could be used in combination with existing drugs, which was brilliant for diabetes patients, because there were very few drugs out there and some people find that therapies don't work for them. The immediate reaction has been one of just absolute panic. Patients have insisted that they be taken off this drug and the share price of GSK plummeted. Few market analysts have estimated that the market share of Avandia, which was around about 10% of all prescriptions for type 2 diabetes patients has fallen to around 0.
Interviewer - Chris Smith
What about drugs like it, because it's one of a family of agents, so are other companies with rival products, are they now worried, were those included in this analysis?
Interviewee - Victoria Gill
The whole class was included in this analysis, but it particularly tackled Avandia because GSK had done such thorough clinical studies and published all of their studies and made them available to regulatory bodies like the FDA, but another drug that's in the same family that is available for prescription Actos, which is produced by Takeda Pharmaceuticals, which is the partner of Lilly and the same reaction has already occurred towards that drug as well. One of the things that has happened at the back of this is that the FDA and GSK have been involved in a meeting in congress in the US and the FDA off the back of this have insisted that GlaxoSmithKline put a black-box warning, which is the most severe type of safety warning you can have for a drug, but this was very different condition, this was for congestive heart failure and apparently critics of the FDA and people within the FDA are now saying that they spotted this pattern a year ago and the FDA did nothing about it. So, there has been a huge amount of reaction from the FDA, from the pharmaceutical industry, from patients, and from clinicians, but it all seems to be so little chaotic at the moment.
Interviewer - Chris Smith
We don't know who the precise patient groups are who are at risk, so you can't say we shouldn't prescribe it to this person, because they could have this side effect, but this bunch they would be okay, we don't know who those people are?
Interviewee - Victoria Gill
Exactly and the general advice is that you mustn't suddenly come off your medication. You must go to your GP and ask advice. But we don't know what really was going to happen with the actual drug it
No comments yet