December
Chemistry World Podcast - December 2012
1:15- The latest findings from the Mars Curiosity Rover's chemistry instruments
4:20- The mechanism behind argyria - 'blue man syndrome' - has been discovered
7:28- Tamara Galloway discusses bis-phenol A
13:38- Making sure 'good bacteria' can get to where it will actually help you
17:25- Can 'living surfaces' act as renewable antibacterial agents?
19:37- Zoltan Takats tells us how he uses mass spectrometry in surgery to detect cancerous cells
26:58- An alternative to the dangerous - but useful - methyl isocyanate
30:42- A less invasive way to deliver insulin, involving a nasal gel, has been developed
33:11- Trivia: Who gave the first Christmas lecture at the Royal Institution?
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Brought to you by the Royal Society of Chemistry, this is the Chemistry World Podcast.
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Interviewer - Meera Senthilingam
This month news from Mars, how silver ions turn your skin blue, injection free insulin and using fungi to keep bacteria away. We also investigate a new way to deliver good bacteria to your gut, how a mass spectrometer is providing more effective tumour removal during surgery and the real risk associated with the infamous bis-phenol A
Interviewee - Tamara Galloway
Both members of the population who have the highest levels of exposure had an increased risk of presenting with cardiovascular disease and diabetes, so more metabolic illnesses, but we didn't see any associations with cancer, with angina, with a range of other health conditions. So, it suggested that what we're looking at might be quite specific.
Interviewer - Meera Senthilingam
Tamara Galloway explains more later in the program. Hello I'm Meera Senthilingam and also with me for this December 2012 edition of Chemistry World are Philip Broadwith, Laura Howes and Neil Withers.
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The Chemistry World podcast is brought to you by the Royal Society of Chemistry, look us up online at chemistry world dot org.
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Interviewer - Meera Senthilingam
First up this month, the Mars Curiosity rover delivers its first data. Phil.
Interviewee - Phillip Broadwith
Yes, Meera. Well, as we all know the Mars Science Laboratory or Curiosity as it is known has been trundling around the surface of Mars for a little while now and the first lot of data from some of the instruments has come back to earth.
Interviewer - Meera Senthilingam
So, what has it been analyzing in what part of Mars and what has come back really?
Interviewee - Phillip Broadwith
Okay, well at this particular stage it is looking at rocks. There are two instruments on Curiosity that analyze rocks. One is called ChemCam which is a laser ablation spectroscopy instrument and the other is called APXS, it's an alpha particle x-ray spectrometer and they both look at rocks but they look at them in a slightly different ways. The ChemCam has a very fine beam and it can look at very small areas whereas APXS, the alpha particle instrument analyzes a slightly bigger area, sort of a couple of centimetres rather than a millimetre or two and gets a more average kind of data.
Interviewer - Meera Senthilingam
And are they looking for different things then?
Interviewee - Phillip Broadwith
Well, Meera the two instruments are kind of complementary. Each one is better at looking at slightly different elements that might be in the rocks, but what the scientists have done is fire them both at the same rock. They've name the rock 'Jake Matijevic' after one of the scientists on the mission who sadly died, to see whether the instruments give the same data back and they agree very well which is a good sign that the instruments have survived the trip to Mars very well and are functioning properly.
Interviewer - Meera Senthilingam
So, it's good that they've agreed, but what kind of insights did it provide; what are the findings then from the two analyses?
Interviewee - Phillip Broadwith
Turns out that there is a slightly higher concentration of alkali elements in the rock than had previously been found in other rock samples and the composition of the rock is very similar to the rocks on earth, have crystallized from magma that's higher in water. So, potentially there was possibly more water on Mars at some point than we thought.
Interviewer - Meera Senthilingam
So, I mean, this is just the first set of data to come back and be looked at, though I guess it's setting quite good precedent for future insight?
Interviewee - Phillip Broadwith
Yeah, absolutely. I mean, Curiosity is scheduled to be on Mars for quite a long time and to look at lot of different rocks so the fact that the instruments are working is really good but there's obviously going to be a lot more data to come.
Interviewer - Meera Senthilingam
Now as well as the rocks though, there's been some insight into some of the gases, in particular methane.
Interviewee - Phillip Broadwith
Yes, well obviously these two instruments are not the only ones on Curiosity. The rover is packed with instrumentation and one of the other instruments analyzes gas in the air or in the atmosphere in Mars and that's particularly looking for methane because methane can both be a precursor to and a product of life on the surface of Mars. So, if they had found methane it would be a good indicator that there either was or could be life on Mars. Unfortunately at the moment, there's very little methane being detected, however that doesn't mean that there isn't any anywhere else. Spectroscopically, from earth we've seen that there is potentially methane but it's not spread evenly across the whole surface of the planet, so it may just be that we're not be in the right place yet.
Interviewer - Meera Senthilingam
Now moving away from Mars, so they haven't been able to find little green men there, but there are big blue men here on earth, Neil.
Interviewee - Neil Withers
That's right and it's quite surprising, you might not expect people to turn blue but there are some people who take colloidal silver suspensions which they use as health tonics because silver has antibacterial properties, so they kind of, the people who take these normally don't believe necessarily in conventional medicines, so they like unusual things and colloidal silver is certainly quite unusual and people who take a lot of this end up with their skin turning up kind of bluey-grey if you ever seen pictures of them on the internet they do look very, very strange.
Interviewer - Meera Senthilingam
So, this is a condition known as argyria and some scientists have now been looking into why this happens?
Interviewee - Neil Withers
That's exactly right. So, Robert Hurt of Brown University in Rhode Island, he knew that the compounds in the body that turn the skin silver or blue were silver sulfide and silver selenide particles in what are called argyrial deposits. So Hurt and his team look at silver nanoparticles in the environment more generally and they realized that the bodies just know their environment, so they looked at the very acidic solution in the stomach and tracked what happened to the silver nanoparticles from there.
Interviewer - Meera Senthilingam
What did they find? What causes this?
Interviewee - Neil Withers
So, it's a quite a complicated process but I will try and get through it step by step. So, the silver nanoparticles in the acidic environment of the stomach turn into silver ions, Ag+, as you might call it and these are able to get into bloodstream because they are attached to lots of different proteins because many proteins have thiols and other ligands in them and like to bind to silver, so the silver ions get into the blood like. Once they are in the blood, they end up in the skin generally. And as you might remember from whatever chemistry you learned about photography, silver ions when they're exposed to sunlight can change back to silver metal. So essentially the skin is kind of turning into a photographic plate almost but on the body. So, then you have silver nanoparticles in the skin and these reacts with sulfur and selenium and again the proteins and the like and they turn into these silver sulfides and silver selenides.
Interviewer - Meera Senthilingam
So, it's quite a few steps that process that they've managed to map out here. But what can be done now that they know this?
Interviewee - Neil Withers
I'm not sure really because I think it is a reversible reaction. I think eventually the blue people do fade back to a more normal colour, of course that's only if they stop taking the silver suspensions which a lot of them don't because they attribute it to how well they feel and they think they feel great and I think some of them secretly like the notoriety that goes with being blue.
Interviewer - Meera Senthilingam
Really?
Interviewee - Neil Withers
Yeah. I think one was a candidate for some political office and he got a lot of extra publicity because he was blue. So, I don't know if this necessarily will solve the problem of turning blue because it's pretty easy to fix it by not taking a suspension of silver, but no one ever really known until now how actually you turn blue from taking this solution. So, that answered that problem.
Interviewer - Meera Senthilingam
Can't say I'd enjoy the attention from being blue but each to their own at least the chemistry is now understood, thank you Neil. And now to a compound that's received a lot of attention throughout the press in recent years and for its risks rather than its benefits, Bis-phenol A. Tamara Galloway from the University of Exeter has been investigating the true extent of this risk.
Interviewee - Tamara Galloway
We are particularly interested in things that interact with hormone systems in the body and these are called endocrine destructors and one of the main compounds that does that is bis-phenol A and it's of interest to us because it's found everywhere. Bis-phenol A is used to make a kind of plastic called polycarbonate which is a very clear rigid plastic and is incredibly useful. And bis-phenol A is made from very cheap reagent, things like acetone and phenol and that makes it quite attractive because it's simple to make. So, it forms a monomer to form polycarbonate and that polycarbonate is used to make many, many different things from CD cases to components of computers, much of the food packaging that we use today particularly the kinds of containers that you might reuse. You might heat things up in the microwaves, things like baby's bottles, things like lunch boxes
Interviewer - Meera Senthilingam
And what really, I guess, started off the whole fear, I guess, of say the risks associated with this compound.
Interviewee - Tamara Galloway
The fear is that when it was originally synthesized in the 1930s, it was synthesized as a synthetic oestrogen and it showed a low level of activity in that regard and it was then put on the shelf because other more potent oestrogen were discovered and synthesized. And it was only pulled off again few years later when it became apparent that it might be useful in the production of plastics. It's not acutely toxic. So you can perform any number of toxicity tests that it won't cost death, it's not fatal, it's not something that's hugely harmful, but what has became apparent is as we've become better at monitoring the concentrations of these compounds in the environment is firstly that it's everywhere. So, you can find it in 95% of the people, if you measure the concentrations in their bodies, you'll find bis-phenol A and that's why it's become a public health risk because of its widespread presence and because it has these oestrogenic properties. And so researchers started to explore what effects the concentrations that are found in people might start to have and they started to throw up all sorts of interesting findings.
Interviewer - Meera Senthilingam
So, how have you been really looking into this with your work and really studying it to see, I guess if the risks are really there?
Interviewee - Tamara Galloway
We are basically interested in the chronic effects of the pollutants that you encounter every day. How might they affect you as an adult if you're looking at chemolytic exposures and one of the first studies that we did was to study the database called NHANES, which is a monitoring program that was set up in America and what it studies is it monitored very large numbers of people for repeated years
Interviewer - Meera Senthilingam
So, the actual levels, say of, bis-phenol A in various populations?
Interviewee - Tamara Galloway
There has never been studies done in populations around the world which have shown that really vast majority of the population has detectable levels in their blood. So, we're talking sort of 90-95% of people. Exposures may not be at a particularly high level, but it's there in everybody.
Interviewer - Meera Senthilingam
And what's the quite range say in the level you say, you've mentioned the levels weren't necessarily high, but was that a quite a diversity?
Interviewee - Tamara Galloway
Yes, there is a quite diversity of exposure. So we do see that some people have really quite high levels in their bodies. Bis-phenol A is one of these compounds that gets quite rapidly metabolized or it does seem to be quite rapidly metabolized. There is evidence that there will be fluctuations from day to day depending on what you're eating.
Interviewer - Meera Senthilingam
And so how will you really follow from this then? So, I mean, you've seen this then. Is it something to worry about or are the levels low enough that it's not a concern. What will you be looking into next?
Interviewee - Tamara Galloway
I think what we had found was that there is an association between those members of the population, you had the highest levels of exposure had an increased risk of presenting with cardiovascular disease. We hypothesize that bis-phenol A might be associated with adverse health conditions but we were not entirely sure what those adverse health conditions might be. So, the association was with cardiovascular disease and diabetes. So, more metabolic illnesses, but we didn't see any associations with cancer, with angina with a range of other health conditions, so it suggested that what we're looking might be quite specific. Subsequently repeated analysis in separate population of over a thousand people and found the same association. What we've then done is we've taken a population of people suffering from cardiovascular disease and matched set of controls and we've looked at samples which were taken up to 10 years before their diagnosis and we've seen the same effects but what that is suggesting is that the exposure comes before the disease.
Interviewer - Meera Senthilingam
And are there any thoughts as to why say they get these diseases in particular in these conditions?
Interviewee - Tamara Galloway
So, we and many, many other groups across the world have been doing laboratory studies to try and answer that very question. At the moment, our best guess is that we're seeing changes in the expression of genes associated with oestrogen but not necessarily just the oestrogen receptor which is one of the main ways in which oestrogen works. So, the effect seemed to be quite subtle.
Interviewer - Meera Senthilingam
And I guess so, I mean, now that you have seen I mean, a variety of studies really, this kind of link here, I mean, what should now really be done, I guess, because there have been certain restrictions put in place, I mean, is this a compound we should be seeing less often but shouldn't be as ubiquitous say, as it is,
Interviewee - Tamara Galloway
I think it's difficult. I mean this bis-phenol A is used to make polycarbonate. Polycarbonate is a very useful substance. If you're going to remove that from the food chain, you have to know what you're going to replace it with and of course many companies are now working on alternative compounds. I think that we need more research to find out what exactly is happening with this compound. But what we're also seeing is that there do appear to be voluntary reductions in usage in which many manufactures are voluntarily removing the bis-phenol A from their products.
Interviewer - Meera Senthilingam
Tamara Galloway from the University of Exeter. Coming up soon, a new way to identify cancerous or diseased tissue in the operating theatre in real time. But before that a way to ensure that all that good bacteria we consume to benefit our health actually gets where it needs to go. Laura.
Interviewee - Laura Howes
We all hear a lot about needing good bacteria in our guts to help healthy digestion. There are lots of probiotic drinks and yoghurts that get sold very much playing up the health benefits, but what they don't know often say is actually our stomach is very good at getting rid of bacteria. Our stomach has a lot of acid in it for digesting proteins and bacteria. So, not a lot of that actually gets through to the gut, to the intestines to where they're actually are needed to helping your gut flora for digestion and help digestion and that's one thing quite healthy individual with good general digestion, but if say you've taken antibiotics which have depleted the gut flora or if you have irritable bowel syndrome, for example, it's really important to try and get more bacteria into your gut into your intestines to help with digestion and general health and well being.
Interviewer - Meera Senthilingam
So, now a group have come up with a way to get around this problem of bacteria dying off in your stomach.
Interviewee - Laura Howes
Absolutely. This is a group from Reading University, and it's a collaboration between material scientists and microbiologists to try and use understood materials to try and protect the bacteria and keep them healthy and safe passing through the stomach acid and then release them where they actually need to go.
Interviewer - Meera Senthilingam
So, how is it possible to pass through, they've developed a coating essentially to protect them?
Interviewee - Laura Howes
Yes, they're actually using a fairly well known materials in particular calcium alginate beads which if you've ever look at molecular gastronomy say Heston Blumenthal or you watch Masterchef, you often see people making sauces and then dropping it into an alginate solution which makes these sort of soft beads that burst in the mouth, a lovely sauce flavour. What these guys are actually doing is making a bacterial solution and then containing that in the calcium alginate gel and then they're coating that in multiple layers of chitosan which is a sugar from crustaceans we've talked about it quite a lot at the podcasts here and also alginate and they do a multiple process, sort of, multilayer one and then the other, building up until they've got quite a nice safe environment for the bacteria.
Interviewer - Meera Senthilingam
So it's quite a few layers to protect it going through but then will it also then be able to deliver in the intestine?
Interviewee - Laura Howes
So they say three is the magic number. If you've got say one layer, when I say one layer that's one layer of alginate and then one layer of chatoyant then you get some problems with leeching before it gets to where it needs to go. If you get too many layers then there's problems with the sugars taking up lots of water and swelling and breaking but they say about three layers is three is the magic number and then it can get into the stomach, pass all the way through and get into the proper intestines where the pH level goes to about seven or eight and that's where suddenly the beads are released.
Interviewer - Meera Senthilingam
So, what would be the next stages really to make this I guess the reality and used in say probiotics.
Interviewee - Laura Howes
Well obviously at the moment, well, they haven't actually used in actual people's stomach. They've been using one for model things like a stomacher which is a mechanical machine with a highly acidic environment that does quite a lot of mechanical swishing around like a stomach does. So they're obviously going to have to test this in actual animal models I guess first. But all of these substances are already approved for dietary use. There is also a problem obviously between making sure that the size of the particles is good for delivery but it doesn't change the taste or feel of the food. So there's still a bit of work to do, but it's more in the tweaking rather than safety protocols or anything like that.
Interviewer - Meera Senthilingam
And well from trying to get bacteria into your intestine, but now keeping them away from your surfaces, Neil.
Interviewee - Neil Withers
So, in hospitals and other environments you don't want nasty bacteria, the bad sorts to infect you. So, one way that you can possibly get rid of the bacteria is by having a surface that released antibacterial agents. So what Wendelin Stark and his colleagues have done is they've made a surface which has got a fungus inside it.
Interviewer - Meera Senthilingam
Surfaces made of fungus?
Interviewee - Neil Withers
Well they're not made of fungus, but they have sort of gaps inside them where the fungus live and more importantly they've got small holes on the surface where small molecules can pass through and get to the fungus. So the idea here is nutrients and food can get to the fungus that way, the fungus eats them and produces penicillin like antibiotics, which can then go out of the holes of the surface and be released and kill the bacteria.
Interviewer - Meera Senthilingam
Is there a problem though, perhaps with resistance or things like that when you're I guess going to have this generic penicillin on many surfaces.
Interviewee - Neil Withers
I guess there's always going to be problems with resistance with any kind of antibiotics so having this just used more generally there may or may not be problems, it's just know the delivery method rather than a different antibiotic, so I guess it's the same kind of problem but used in a different way.
Interviewer - Meera Senthilingam
So what kind of stage is it used in now, and is it something that's feasible really, I guess to cover, I guess well in hospitals, may be kitchens or so on.
Interviewee - Neil Withers
I guess kitchens would be one of the best places to use them because food is being spilled there, so there'll be food for the fungus. But I think at the moment the key is that it might not be as robust as chemical treatments or things that release chemicals through having little pockets of antibacterial things, but the point is that it's renewable. So if you have a little pocket of an antibacterial agent, eventually that will all be leeched out, and so after a year or two years however long it won't be antibacterial anymore but because the fungus is alive as long as you feed it, will produce more of the agent. So that's where the real advance in this one is. One of the independent experts who commented on this said he wasn't sure about how long the fungus would actually survive in these things, so there is a question of how stable they are and how long they live. So I guess you'd need to keep an eye on that.
Interviewer - Meera Senthilingam
So watch this surface. Now one of the current challenges in the fight against cancer is ensuring that when a tumour is removed, that you also remove the cancerous or precancerous cells surrounding it to reduce the chances of the cancer coming back and now a new technique is providing this level of insight in real time, using the well known chemical technique of mass spectrometry.
Interviewee - Zoltan Takats
My name is Zoltan Takats. I'm a reader in medical mass spectrometry at Imperial College, London. My main area of research is mass spectrometry and the application of mass spectrometry in clinical diagnostics. Our main hypothesis is that different tissues with different disease have different chemical composition. And if we manage to get information about this chemical composition, then we have a chance to come up with a diagnosis and we're also developing a method which can give these chemical information within fragment of a second and if we use these kind of methods in clinical diagnostics, then we can eventually develop methods which give immediate diagnosis.
Interviewer - Meera Senthilingam
Now when you say disease tissues, I mean, in particular, you're focusing on cancerous tissues and precancerous tissues and non cancerous tissue, so how does the chemical composition of these vary.
Interviewee - Zoltan Takats
What we're trying to do is looking at the whole chemical composition of the tissue and looking at changes at the pattern level, cancer tissue and the surrounding tissue have the same molecular set, so we cannot really define any good specific biomarker for that tumour, especially if it's in the early stage of the disease, but the distribution of these molecules will be markedly different. They are built up of the same kind of bricks but in one case, there's a little bit more of this one and little bit less of that one and the other way around in case of the healthy tissue.
Interviewer - Meera Senthilingam
So you're looking for this kind of difference in their composition or organization.
Interviewee - Zoltan Takats
Yes, exactly.
Interviewer - Meera Senthilingam
And do you have perhaps an example of say a marker or a composition that would differ, in say, a cancerous and healthy tissue.
Interviewee - Zoltan Takats
Biomarker discovery generally focuses on proteins and in many cases, one can find specific tumour specific proteins, but this is not a universal thing, so in many cases, in many other cases, you cannot find a good protein biomarker. What we're looking at is a set of phospholipids, membrane lipids, so the building blocks of cellular membranes, and what we' found is that the phospholipids composition of cell membranes is quite different for any kind of different tissue including the disease tissue. So you can say that whatever can be differentiated using histology, we can differentiate it based on the phospholipids content of tissues.
Interviewer - Meera Senthilingam
So using this insight now, you've essentially tried, you've created surgical equipment, a surgical knife that has mass spec as part of it to try and see this kind of difference in composition of tissues, as a surgeon is cutting into cancerous tissue or tumours.
Interviewee - Zoltan Takats
What we've realized is that electrosurgery in any form, whether it's used for dissection or coagulation, it converts certain chemical constituents of tissues, mostly the membrane lipids into gas based ions, so gas based charged particles. And if we take these gas phase ionic species into a device called mass spectrometer, then we can directly analyze the chemical composition of the tissue.
Interviewer - Meera Senthilingam
You've shown me a video of this really in action, in the operating theater and you can see that as a tumour is being removed, there is this kind of smoke being created and alongside that you can see the mass spectrometry and the various kind of chemicals that are coming off. This is all really happening in real time, to immediately see, I guess what the composition is of the tissue is you're currently cutting.
Interviewee - Zoltan Takats
Yes, the challenge is rather how to convert the spectroscopic information into medical information.
Interviewer - Meera Senthilingam
So I guess, yes, how would this work in practice?
Interviewee - Zoltan Takats
The challenge is to compare your real time unknown spectrum to thousands of authentic spectra. We have a database, currently we have close to hundred thousand individual entries in this database, so spectra of identified tissues, and we have to compare for real time spectra in every second to this dislodge database, getting a feedback to the surgeon is still a problem, giving the feedback without destruction. One way to do it is a visual display as you've seen on the screen, so we can give a colour coded signal to the surgeon, which can be followed without staring at the screen, but we're actually working on different approaches, we're trying to convert it into a musical sound.
Interviewer - Meera Senthilingam
So that they don't have to look away.
Interviewee - Zoltan Takats
Yes, exactly.
Interviewer - Meera Senthilingam
So, currently you've got it, so there's kind of a red colour appearing when it's cancerous tissue, and that's with the mass spec kind of going on the chemicals that are coming off, and then I guess, as they get to sort of reaching the healthy tissue, it's changing into a green colour to tell them to stop cutting.
Interviewee - Zoltan Takats
Yes exactly and we can further refine this, I can imagine a continuous colour system which the surgeon can follow.
Interviewer - Meera Senthilingam
So what kind of stage is this is all at now?
Interviewee - Zoltan Takats
Yes the device is being used in operating theatres; but at the moment the surgeon doesn't have particular permission to make decision based on our data, so the whole system is learning at the moment.
Interviewer - Meera Senthilingam
Is this something that's universal across all types of cancer?
Interviewee - Zoltan Takats
At the moment we are looking at different tumour environments, we're not only looking at cancer but looking at chronic inflammatory diseases, inflammatory bowel diseases. We don't really see...
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