Chemistry World Podcast -October 2010
00:12- Introduction
01:20 - Cement chemistry partly to blame in BP oil spill
04:33 - In full flight: making cruise emissions count
06:55 - Universityof Essex's Chris Cooper gives us an overview of the current research into artificial blood
14:38 - Oyster glue's secret ingredient
17:38 - Are nanotubes the future for radiotherapy?
20:50 - Cole DeForest, University of Colorado, on using click chemistry for biological applications
27:51 - Comet shockwaves helped stimulate life on earth
30:24 - Growing magnetic leaves
(Promo)
Brought to you by the Royal Society of Chemistry, this is the Chemistry World Podcast.
(End Promo)
Interviewer - Meera Senthilingam
This month a new revelation into the BP oil spill, the use of nanotubes to target radiotherapy, the cost of the environment of us cruising through the air and how comets help stimulate life on earth. We also discover how the field of click chemistry is transforming stem cell research as well as the latest development in the search for blood substitutes and the benefits these could provide.
Interviewee - Chris Cooper
Because it's long lasting, you could leave it in. it could be an ambulance; on the top of the mountain of Afghanistan; it could be with a remote doctor who's in Australia; it could be in the African bush. So you have this ability to be able to go anywhere with the product, keep it offsite or stockpile it for emergencies.
Interviewer - Meera Senthilingam
Essex University's Chris Cooper will be explaining the challenges faced when developing these substitutes and how his team are trying to overcome them. So all that coming up in this October edition of Chemistry World with me Meera Senthilingam and contributors this month Phil Broadwith, Andrew Turley and Anna Lewcock
(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)
Interviewer - Meera Senthilingam
First up this month, more revelations into the cause of the BP oil spill, Phil.
Interviewee - Phillip Broadwith
Okay so BP has put out a report saying that there were eight things that specifically went wrong that contributed to the massive oil spill and explosion that happened in the Gulf of Mexico earlier this year. And one of those, in fact the first one that they identified was to do with the cement. The cement job that they were trying to do is part of the standard procedure for finishing off drilling a well. You have to seal the bottom with cement so that you have a stable hole drilled in the earth and then you can start pumping the oil out, but to do that you have to get the cement down there to the bottom which can take quite a while if it is a deep well, so you have to have cement that is fluid enough to get down there and will then cure properly at the high temperatures and pressures that are down there in the bottom of the well.
Interviewer - Meera Senthilingam
So what was actually found then to be wrong with the cement as it had gone down and who has been looking into this.
Interviewee - Phillip Broadwith
The way that they were trying to make the cement fluid enough and get it flow down the well was by making a sort of foam with nitrogen gas. That makes the cement lighter and it also makes it more fluid so they can pump it down, spread out around the bottom of the well where it needs to be, and then as long as the foam stays as a foam, everything is fine. But what they found was the foam is likely to collapse under the conditions at the bottom of the well which means you get this thing called nitrogen "breakout". Nitrogen "breakout" is bubbles forming in the cement which make channels through the cement as it is drying which means that you then have holes and a porous structure that the oil and gas can get can seep through and then can escape up to and out of the well.
Interviewer - Meera Senthilingam
So this "breakout" was thought to have happened then?
Interviewee - Phillip Broadwith
That's what BP is saying. The picture gets a little bit less clear when you consider that the cement that they have done these tests on is not the actual cement that went down the well. So, it's quite possible that there were different additives and all things like that. And it's not just about the cement chemistry either, you got to get the cement in the right place which involves the whole engineering project of having to do the job and it's also some of the bits and bobs you need to get right, so that the cement spreads out around the bottom of the well in a sort of even way to make a good plug.
Interviewer - Meera Senthilingam
So now that there's the importance of say, the cement has been found out is this then going to be useful perhaps just in other oil rigs.
Interviewee - Phillip Broadwith
Well something that BP has identified in its report is that there might have been some problems with the cement. So, it's something that people are obviously going to have a look at a little bit more closely each time. Something that came out was that this process of using nitrogen to make the cement fluid, the conditions that were in the deep water horizon well are right on the limit of what's been done before with this kind of technique. So, it was possibly a little bit risky anyway, maybe we need to look at some different things to add to the cement rather than nitrogen that won't cause this "breakout".
Interviewer - Meera Senthilingam
Okay, so well avoiding anything like that in the future is obviously crucial, but now moving on from that environmental concern to another one and that is aircraft emissions, Andrew.
Interviewee - Andrew Turley
So this story is about aircraft emissions, but not carbon dioxide, which we've obviously heard a great deal about in recent years. This is about particulates, small bits of dust and grime that come out as traditional sort of pollution. What these researchers have found is that 80 per cent of the total health impact from aircraft emissions at ground level is coming from the cruise phase, so this is the main flying segment of the plane. Whereas in the past, scientists have focused on the take-off and landing.
Interviewer - Meera Senthilingam
Well so, how has this insight come about? So who's been looking into it and how big concern really are the emissions then during cruising?
Interviewee - Andrew Turley
Well, the researchers from the Massachusetts Institute of Technology in the US and they've modelling this to work these out. One of the most unfair aspects of this is that, even if much of the flight patterns, much of their traffic originates outside of Asia, the burden of these health effects lands in Asia.
Interviewer - Meera Senthilingam
But what's actually causing the problem then in these emissions?
Interviewee - Andrew Turley
The problem is aerosols. So these are droplets of liquids, in this case nitric acid and sulfuric acid and these are damaging the people's health.
Interviewer - Meera Senthilingam
And what makes them particularly damaging, say in the region of Asia, why that particular continent?
Interviewee - Andrew Turley
Well it is farming that is exacerbating the problem in that region because the nitric acid can react with high concentrations of ammonia, mainly from farming, and this can form ammonium nitrate.
Interviewer - Meera Senthilingam
What else can be done knowing this information? Should government be taking this on board or what's hoped to happen?
Interviewee - Andrew Turley
Well, it's really just another reason for us to reduce our air traffic generally. Something I've heard from atmospheric chemists in the past is that while a lot of the attention is being focused on climate change and carbon dioxide emissions, we really should be thinking of this more holistically alongside pollution at ground level from particulates.
Interviewer - Meera Senthilingam
So there's more to flying than just take-off and landing. Thanks Andrew. Now you may have come across the recent wave of vampire-related fiction in our books and on our screens, where these blood sucking characters are living in harmony with their human counterparts. Thanks to things like synthetic blood. But in the real world, this is an area scientists haven't quite reached and have been working on for a long time. Well, not feeding vampires, but developing artificial blood substitutes to provide a more comfortable and accessible bank of blood to call on and it's all quite complicated, as Chris Cooper from the University of Essex explained.
Interviewee - Chris Cooper
Well there are two different classes of blood substitutes; I would call one chemical blood and one biological blood. The chemical blood just consists of molecules that can dissolve oxygen very effectively. These are molecules, they are called the perfluorocarbons, they are very inert, they are very unreactive with anything and they just dissolve lots of oxygen. And a molecule of that class was the first one was officially allowed to be used as blood substitute in the US. It's no longer used, but still a version of that is in use at very few parts of Russia, but it's not used in a widespread way. So that's the chemical blood. The alternative, which is of much more interest and many more products tend to be developed is what we call biological blood and that takes the red part of the red blood cells, the haemoglobin and what it does is try to make it active and still able to carry oxygen outside the red blood cell and most products have gone down that route and most of the research is in that area, but it's not exclusive.
Interviewer - Meera Senthilingam
And I guess the problem really then, one of the main obstacles is actually haemoglobin in these substitutes, is that right?
Interviewee - Chris Cooper
Yes, I suppose it's both the greatest benefit and the greatest boon, the haemoglobin. So it's a wonderful molecule because it can carry oxygen around the body really, really effectively. But it could also do other chemistry. So, unlike the perfluorocarbon, which is a completely inert chemical, the haemoglobin, which does the job of carrying oxygen much better, is chemically reactive and that's the problem.
Interviewer - Meera Senthilingam
So, how are you setting about kind of researching this area now? So what do you focus on in order to develop hopefully useful artificial blood?
Interviewee - Chris Cooper
Well, there are two chemical problems, if you like, with the haemoglobin neither of which we think relate to its normal function of oxygen transport. It gets rid of your good radicals and it makes bad radicals. So it all relates to free radical biology. And obviously free radicals, every chemist knows are reactive species. What haemoglobin can do is it binds nitric oxide and nitric oxide is a signalling molecule, a gas in the body that controls blood flow and blood pressure and a whole range of other physiological parameters. Haemoglobin can scavenge that nitric oxide, that's potentially a problem and it can cause blood pressure changes and blood flow changes. That's one problem - the removing the good radical. The second problem is that haemoglobin also can create oxygen-based radicals by reacting with hydrogen peroxide or lithium peroxide that are always in the body and it's especially likely to do that when it's outside the protective environment of the red blood cell. What we're doing at Essex is trying to alter the haemoglobin, so it doesn't do the second part of that chemistry, the oxygen radical part; we're not doing the nitric oxide part as yet.
Interviewer - Meera Senthilingam
So, given with your actual product, how does this actually work then to actually function as blood?
Interviewee - Chris Cooper
So, what we discovered is that there are pathways in the haemoglobin molecule that are responsible for these free radicals being removed, these dangerous free radicals and the body does have compounds that it uses to remove the free radicals. One of these is vitamin C, ascorbate, which you've got in your blood, in your plasma. So we put a blood substitute into the plasma, and the ascorbate is one of the key ways of detoxifying these radicals and what we've done is genetically engineer the haemoglobin molecule to create new biological pathways, to make it easier for the ascorbate to get rid of the free radicals. So, it's simply like enhancing the body's own defence mechanisms.
Interviewer - Meera Senthilingam
Where are you currently with this work? How far away do you think we are then from this small, kind of biological form of artificial blood?
Interviewee - Chris Cooper
So, if you're asking about how far we are at Essex, we're still really in this studying the effect on the cells and trying to optimise our lead compound if you like. If you ask about how far the world is, there is still a compound going through clinical trials made by a company called Sangart. We don't know yet, whether it'll work or not and it's going through a quite complicated clinical trial in trauma patients at the moment. So I always answer that question really by saying that it could be a clinical product in 2 years or 10 years.
Interviewer - Meera Senthilingam
And I guess the big question is always cost as well. So, how expensive will these products be when they're actually on the market or is that just not known yet really?
Interviewee - Chris Cooper
I think it's not known because of the scale of how you make them, I mean, the thing about making blood products is that you're making them sort of pharmaceutical at an amount that nobody has tried before, but the idea would be to be competitive with blood. Of course blood is not free because although it's wonderful that people give their blood free at least in the UK, all the testing and the packaging of it costs money. So the blood costs about ?200 a unit in the UK. So you obviously want to be able to make a unit of artificial blood competitive with a unit of real blood.
Interviewer - Meera Senthilingam
And if this were to become available, how useful or how advantageous do you think it would be, just in relation to donated blood?
Interviewee - Chris Cooper
Well let's say that we had artificial blood that was completely equivalent to blood in terms of its normal use, the advantage you'd have with artificial blood was it would be much more long lasting. So normal blood, we have to get rid of it in 42 days. One of the products lasts a year already. That's been in clinical trials. So, you could. its long lasting and therefore some of the problems with having to get rid of all your blood within 42 days and having to throw some away would not be there. Because it's long lasting, you could leave it in places like, it could be an ambulance; on the top of the mountain of Afghanistan; it could be with a remote doctor who's in Australia; it could be in the African bush. So you have this ability to be able to go anywhere with the product, keep it offsite or stockpile it for emergencies. So that's a major issue. There's a very small problem with blood that it's mis-typed and that's always some very small human error. But because so much blood is used, you do occasionally get those mismatches. That shouldn't be a problem with this product. I'd say that's a rather minor benefit. But certainly the fact that you could have a generic blood, you could give it anywhere and could be long lasting is important and I'll just make one other point, although our blood is safe at the moment, it's not tested for every virus. Now the ones it's tested for are not really a problem at the moment, but if a new HIV came up, there are lot of people unfortunately who have caught Aids from blood transfusions. You would remove that possibility forever, if you had an artificial blood.
Interviewer - Meera Senthilingam
So plenty of important advantages there, reducing the risk and increasing accessibility and storage options. That was Chris Cooper, professor of biochemistry at the University of Essex.
Jingle
End jingle
Interviewer - Meera Senthilingam
This is Chemistry World with me, Meera Senthilingam. And still to come, we investigate a relatively new field of chemistry that's transforming the field of tissue and organ regeneration. But first Anna, a sticky insight into the world of oysters.
Interviewee - Anna Lewcock
Yes, so Jonathan Wilker and his team at Purdue University in the US and colleagues at the University of South Carolina have managed to identify the added ingredient that distinguishes oyster glue from the glue of other marine species like barnacles or mussels.
Interviewer - Meera Senthilingam
So what have they found? What is that distinguishes it?
Interviewee - Anna Lewcock
Oysters build these enormous reefs that are made of billions of oysters that they stick to one another and they build these massive shellfish walls that tens of metres deep and several square kilometres in that area. So they're really huge constructions, but there's not much, that's actually been known about how they do it and what that glue to hold it all together is made of. So the team used a range of spectroscopy and analysis techniques to look at the glue and they compared it to that of mussels and barnacles to see if there is any difference. The glues of mussels and barnacles are mainly protein and they found some crosslinked proteins in the oyster glue, so there were some similarities there, but that's about where the similarities ended. Barnacle glue, for example, has about ten times the water content of oyster glue, but the biggest difference that they found between the oyster glue and the glues of other shellfish marine species was that the oyster glue contains a very high proportion of inorganic material like calcium carbonate and it's this inorganic-organic hybrid that makes up the oyster cement and makes it different from that of other marine shellfish species.
Interviewer - Meera Senthilingam
But why does this increase say in inorganic compounds make it a better adhesive.
Interviewee - Anna Lewcock
The kind of difference between is that the glues that are in barnacles and mussels for example are kind of a soft, possibly more liquidy glue, whereas the low water content and high inorganic content in the oyster glue makes it more of a cement and therefore probably a stronger adhesive.
Interviewer - Meera Senthilingam
And so what kind of things could this be used in?
Interviewee - Anna Lewcock
Well there's several aspects to this really. There's massive reefs that I referred to earlier. They actually form quite an important habitat and ecosystem for other species and they've actually been destroyed quite a lot. In some areas, the oyster population has been reduced by over 90 per cent because of pollution, overfishing, that kind of thing. So, it's hoped that a bit more insight into things like the oyster cement would help to reintroduce oysters back into those habitats and the other thing they said that you'd be able to form synthetic versions of these adhesives that could be useful perhaps in medical implants and that kind of thing. But also the insight into how the cement works means they also might be able to develop coatings for example for the bottom of ships that would stop these oysters sticking in the first place. So the added insight would be able to be used to protect vessels as well.
Interviewer - Meera Senthilingam
And the use of this as a protectant then would actually have benefits compared what's currently used as well.
Interviewee - Anna Lewcock
Absolutely. At the moment, a lot of the antifouling materials are based on copper, for example, which isn't too good for the environment when it starts leaching out of the paints and things that they use on the bottoms of ships at the moment.
Interviewer - Meera Senthilingam
Okay, well thank you Anna. And now moving over to some potential biological applications, there's been recent work in the use of nanotubes in the fight against cancer.
Interviewee - Phillip Broadwith
Yes Meera. There have been a lot of people talking for a long time about using nanotubes to deliver drugs and this is one of the first actual examples of somebody putting a therapeutic agent inside a nanotube and delivering it to a specific area of the body. It's been done by Ben Davis from the University of Oxford and what his group have done is work with Malcolm Green who is also at Oxford, who recently developed a way of filling carbon nanotubes with stuff. So, the stuff in this case is sodium iodide. If you use the radioactive isotope of iodine in your sodium iodide and seal it inside the carbon nanotube, you've then got a kind of little deliverable radiation pill almost that you can take to whatever area in the body that you'd like.
Interviewer - Meera Senthilingam
But say, with this isotope in the nanotube, how would it actually be released and how would it be released in the right place as well?
Interviewee - Phil Broadwith
Okay, well that's the beauty of it Meera. You don't have to release the sodium iodide. In fact you don't want to. So these nanotubes are quite, slightly different from normal nanotubes, in that they're completely sealed at both ends with the sodium iodide inside. What you're then delivering is radiation. So, the photons of the gamma rays can get out in between the gaps in the molecule of the carbon nanotube. So, you're essentially delivering radiation to exactly where you want it. So all you then have to do is find a way of targeting the nanotube and what Ben Davis's group has done is attach a molecule to the outside that has a particular kind of sugar on it, which binds to a protein that's present in the lungs.
Interviewer - Meera Senthilingam
And what is the sugar then and how does this ensure that the tube gets to the lungs and also could you perhaps attach other things as well to get it to different locations?
Interviewee - Phillip Broadwith
Well yes. That's exactly the idea. At the moment they've got one type of sugar, N-acetylglucosamine, it's a particular arrangement of N-acetylglucosamine. It binds to one specific protein that happens to be in the lungs. The problem is we don't have a map of all of the sugars that bind to different proteins in different parts of the body or on different tumours. That's kind of the next stage, but you could also think about using antibodies attached to the outside to target the nanotubes as well.
Interviewer - Meera Senthilingam
What about risks? Are there any risks associated with this?
Interviewee - Phillip Broadwith
Okay. Well there's been quite a lot of talk about the toxicity, or not, of nanotubes and we've had several stories about it in Chemistry World, but talking to Professor Davis, he was saying that they've done some toxicity experiments. They don't see any kind of evidence of the nanotubes breaking down in the body and then because they're quite short these nanotubes, they don't have so many of the toxicity problems like much longer nanotubes acting in the same way as asbestos for example. So all they see happening to these nanotubes is that they go to the liver and spleen and they're just cleared out of the bloodstream in a normal kind of excretory system.
Interviewer - Meera Senthilingam
And finger crossed, it proves effective. Thanks Phil. Well moving onto a reasonably youthful field of chemistry now that's been shown to have applications across many areas of science; and that's click chemistry. One scientist using this on stem cells to further our prospects of tissue and organ regeneration is Cole DeForest from the University of Colorado. He explained more about just what click chemistry is.
Interviewee - Cole DeForest
Click chemistry basically refers to a chemical philosophy that was introduced by Barry Sharpless of the Scripps Research Institute of California back in 2001. And so this chemical philosophy really refers to a class of reactions that meet a number of criteria. Some of this criteria include that they proceed very quickly under mild conditions as well as in a variety of solvents or perhaps mostly importantly of all, they proceed extremely selectively meaning that the presence of the other functional groups in these reactions doesn't interfere with the desired reaction. So the most common of the quick reactions is the so called Huisgen 1,3- dipolar cycle edition, which involves the copper catalysed addition of azide to a terminal alkyne. This reaction has really been used in just about every field from polymer synthesis and modification to drug discovery, DNA modification and nanotechnology. This reaction really has proven to be the poster child of this so-called click revolution. More recently, another reaction of interest that's called the thiol-ene reaction has reached this click status and this thiol-ene reaction involves the radical mediated addition of a thiol across a carbon-carbon double bond. Now this reaction has a benefit over the Huisgen reaction in that it can be initiated and controlled with light, which ultimately enables the reaction to be controlled spatially as well as temporally giving the user control over where both in space and time of this reaction will occur. So this reaction has actually been used to selectively pattern substrates including DNA microarrays and microfluidic devices. But really those are the two main reactions of the field of click chemistry to date.
Interviewer - Meera Senthilingam
So is it fair then to summarise the reactions involved with click chemistry as reactions where you can essentially build up the addition of the chemical groups to each other.
Interviewee - Cole DeForest
Yes that's exactly right. So the idea behind click chemistry is that you're clicking multiple moieties together in an extremely controlled and quick and efficient manner.
Interviewer - Meera Senthilingam
And so within this area though, you're using stem cells.
Interviewee - Cole DeForest
That's correct. Because these click reactions are so selective, we can develop systems where multiple functionalities can be incorporated into the same platform. So in our case, we actually use the first of the click reactions the Huisgen reaction to form hydrogel materials in the presence of cells, which ultimately trap these cells in a supportive 3D environment. Now we use hydrogels because they have high water content and a tissue-like elasticity which adequately mimics the cell's natural environment. Now these materials, hydrogels, have actually been used to study in culture cells in 3D for a number of years. It may ultimately form the basis for the field of tissue engineering, which is what we're interested in. But once we form these materials using this first reaction, we can come back and build upon using the thiol-ene reaction and we can actually come back and decorate our hydrogel network with molecules of interest. So these molecules include growth factors, proteins, peptides as well as just basic chemical moieties be able to detect as well as direct cell behaviour in three dimensions. So in the case of stem cells, what we're interested in is being able to use these patterned molecules to actually induce differentiation of cells down different user-defined lineages. So this really opens up the door for starting with the initially homogeneous population of stem cells, patterning in molecules that will spatially pattern in areas of differentiation within the cell population in a way that ultimately mimics how the native tissue forms, in a way this technology ultimately enables us to build up printing three-dimensional organs within hydrogel material.
Interviewer - Meera Senthilingam
So you're largely suspending and keeping stable these stem cells but then using the other reaction to try and lead or direct the differentiation of these stem cells into the types of cells you'd like them to form.
Interviewee - Cole DeForest
Yeah, that's exactly correct.
Interviewer - Meera Senthilingam
So where are you currently with this? So what's been possible so far, what lines of differentiation have you been able to go down?
Interviewee - Cole DeForest
So we've mostly been working with human mesenchymal stem cells and these cells are ultimately are what's responsible for differentiation into bone, cartilage as well as fat cells. So we kind of envision being able to engineer sort of new knee joints where cells are initially in this hydrogel material and then we can direct spatially these cells to become both the bone as well as the cartilage interface that ultimately makes up this new knee. So now we're actually in the process of going about, verifying that we have successfully pushed these cells down, whatever lineages that we're aiming for and going about trying to just see that the cells that we've induced this behaviour in are really behaving the way that we would expect them to in the body as well.
Interviewer - Meera Senthilingam
Is it then possible with cartilage, you would then be pursuing all the other different types of cells in our body as well then?
Interviewee - Cole DeForest
Eventually yes. We're kind of in an interesting area where we work very closely with a lot of the molecular biologists, who are making great discoveries as far as what chemical factors are ultimately responsible for the differentiation of these different stem cells down a variety of lineages. So as they continue to make discoveries about what molecules are important, we can go about engineering them into our materials to direct different cell types down these differentiation paths.
Interviewer - Meera Senthilingam
This is really though
No comments yet