Chemistry World Podcast - September 2007
Music
(Promo)
Brought to you by the Royal Society of Chemistry. This is the Chemistry World Podcast.
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Interviewer - Chris Smith
Hello! Welcome to the September edition of the Chemistry World podcast with Mark Peplow and James Mitchell Crow. I am Chris Smith. On the way, how the legacy of Chernobyl lives on.
Interviewee - Mark Peplow
A group of researchers are claiming that radioactive fallout from the Chernobyl disaster has actually impaired the mental developments of Swedish children that were still in the womb at the time of the incident.
Interviewer - Chris Smith
That is the evidence after scratch. Well we'll find out shortly. We'll also be hearing how banned substances likes LSD might hold the key to new cures for common conditions.
Interviewee - John Halpern
When they took LSD or psilocybin, they didn't continue to have these exquisitely painful headaches or sometimes called suicide headaches because people will kill themselves, some of them, to escape the torture of this condition.
Interviewer - Chris Smith
And do you know, what's in your dinner? The chances are you may well have been consuming things that you haven't planned to eat because food fraud is big business.
Interviewee - Peter Barry Ottaway
Food fraud is an amazingly large problem worldwide in terms of commodities such as fruit juices, it runs into hundreds of millions of pounds in some smaller ingredients uses more amounts that are very high value, it probably still runs into millions of pounds.
Interviewer - Chris Smith
Plus we'll be taking a look a date question, which is well, a hangover from last month"
Interviewee - Stefan Cambridge
Hi! This is Stefan Cambridge. Why does the hair of a dog work as a hangover cure?
Interviewer - Chris Smith
Well, it's not a medical myth at all and the answer might just surprise you. It's coming up later in the program.
(Promo)
The Chemistry World Podcast is sponsored by AstraZeneca -- World Leaders in Pharmaceuticals. For a career with AstraZeneca, look us up online at AstraZeneca dot com.
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Interviewer - Chris Smith
First this week, over 11 years since it happened, the legacy of Chernobyl lives on, in babies that were in utero at the time, it seems, Mark.
Interviewee - Mark Peplow
Yeah! This is a really interesting study actually. A group of researchers are claiming, the radioactive fallout from the Chernobyl disaster, has actually impaired the mental developments of Swedish children that were still in the womb at the time of the incident. Now the Chernobyl nuclear reactor exploded back in April 1986 and it sends a cloud of radioactive material drifting over Europe. Now a group of economists, interestingly, at Columbia University in collaboration with a researcher at Stockholm University have now carried out an analysis of more than half-a-million Swedish children that were born between 1983 and 1988 and what they found - they've looked at their academic achievement over that period and they found that when you look at the children who were between 8 and 25 weeks old in the womb at the time the Chernobyl's fallout drifted over Sweden, you see a blip, a down-blip in their academic performance.
Interviewer - Chris Smith
This is done on the basis of IQ or something like that?
Interviewee - Mark Peplow
Well it's done on the basis of the fact that Sweden seems to have quite a rigorous educational system and records that they can actually look at their grades and also whether they qualify for high school or not because there is a qualification exam there. So what they found is that children born in this period, August to December in 1986, which is just a few months after Chernobyl exploded, were 4% less likely to qualify for high school and they had 5% lower grades in average compared with other children born in different times.
Interviewer - Chris Smith
Have they any ideas as to why they're seeing this? It's not just a small blip, because that is quite a small difference, isn't it?
Interviewee - Mark Peplow
It is a small difference and this is one of the many reasons why this is, I'm sure, going to be quite a controversial study. This is something, like I said, they pulled out the statistics, from looking at more than half-a-million children. The effects, of course on development in the womb at this period, 8 to 25 weeks post conception, is probably the most vulnerable period for a child's development, so any kind of effect on the mother, any kind of strain on their system is potentially going to have an effect on the child. Now one of the sources of controversy that I mentioned is the fact of course these people are economists, they are very well used to dealing with statistics which is how they've done the study, but normally when people look at the effects of Chernobyl, It's like radiation physicists and environmental monitoring people, things like that And.
Interviewer - Chris Smith
So what are those, sort of, parties think it is?
Interviewee - Mark Peplow
Well we went back and talked to a variety of people that are well used to looking at these sorts of studies and while, of course, this study doesn't prove, of course an effect. It only proves an association between the timing of Chernobyl's fallout and the timing of these children's academic performance. On the whole, the reaction was that the statistical method they used looked sound and in fact another of the researchers that we talked to, James Smith, who works at the University of Portsmouth says that this study appears to have control for some factors of uncertainty quite well and they should now go on and do a similar analysis in neighbouring countries to really know, whether this has happened.
Interviewer - Chris Smith
And another reason why you mustn't wear Russian underpants, because of Chernobyl fall out. Now James some interesting work is also ongoing in terms of how we clean up our wastewater act, because we could be in trouble in the future.
Interviewee - James Mitchelle Crow
That's right. Well, you might think that the water coming out of sewage plants would be pretty clean, but it's actually not as clean as it looks. Certain molecules, in particular, drug molecules and pesticides are passing through these treatment plants, completely unscathed and so over time they are accumulating in the water system.
Interviewer - Chris Smith
Why aren't they being removed? Is there some particular chemical reason why they accumulate like this?
Interviewee - James Mitchelle Crow
They are not being removed because they are resistant to breakdown. Some of them have unusual structures that are not necessarily found in nature and so there's probably not that many organisms that will be able to breakdown that sort of structure.
Interviewer - Chris Smith
So what are the consequences of something like this building up in the way you described and by how much have they gone up?
Interviewee - James Mitchelle Crow
Well certain compounds have gone up about 60 times over a 30-year period, so in surface water, about 30 years ago, these things were kind of at nanogram quantities per litre, now they are up to microgram levels and so if that trend continues then we could have problems and in particular as pressure on water resources grows, we're going to have to recycle our waste water a lot more.
Interviewer - Chris Smith
I guess the key question is, is this actually likely to be a problem for human health though? It's very well to say, well these chemicals have increased, but do we have any direct evidence that is a problem?
Interviewee - James Mitchelle Crow
The evidence at the moment is not clear, I don't think, on exactly what effect they might have, but the concern that this will become a problem in the future and so these researchers in Italy have been working out ways to try and tackle this problem and breakdown these molecules that are coming out of the waste water using a combination of techniques. They found that these compounds are amazingly robust. They have to use a combination of photocatalysts and titanium dioxide, ultraviolet light and also microwave irradiation to be able to break these things down.
Interviewer - Chris Smith
Is the answer to just break them down or should we be encouraging people not to use them in the first place; I mean, surely that's going to be a better solution, isn't it.
Interviewee - James Mitchelle Crow
Well, some of these compounds are good, important drugs; for example, one of them is naproxen which is a non-steroidal anti-inflammatory, which is used in arthritis, others are good insecticides and herbicides, so these compounds do have their important uses. It's just a case of, can we break them down once their use is finished?
Interviewer - Chris Smith
Thanks James! Now from drugs in wastewater to drugs in trials and how safe they are? It's recently been found that the drug rosiglitazone, which is marketed as Avandia may be triggering heart attacks in vulnerable patients. By why wasn't this picked up in trials? Well, Cliff Rosen thinks we need a re-think with more emphasis on patients than on biochemical measurements.
Interviewee - Clifford Rosen
Rosiglitazone which goes under the brand name Avandia, is an activator of PPAR gamma which is a nuclear receptor, which when activated, by drugs like Avandia, can stimulate glucose transport and also fat differentiation. In this particular instance, the major effects appear to be insulin-sensitive cells such as fat cells and muscle cells.
Interviewer - Chris Smith
So, they are good because they lower blood glucose by.
Interviewee - Clifford Rosen
They lower blood sugar rather dramatically and they don't do it by stimulating the pancreas unlike some of the other drugs like insulin. These drugs actually sensitize the cells to insulin, so that you are not adding more insulin to the system. You are just making whatever insulin is around more sensitive.
Interviewer - Chris Smith
That sounds really good, so what went wrong?
Interviewee - Clifford Rosen
I think what went wrong was the fact that when we test drugs for diabetes, the primary endpoint for all our studies has always been lowering the blood sugar, which is measured by haemoglobin A1c. So when these new drugs were discovered, they were found to lower blood sugar and reduce the haemoglobin A1c, much more so, than some of the other drugs. So that prompted the FDA and the European Regulatory Agency and everything to jump aboard and say, "Look these drugs are relatively safe, the six-month studies look reasonably good and they clearly lower sugar, which is the main end-point for diabetic management any ways."
Interviewer - Chris Smith
So, when did that silver lining turn cloudy then?
Interviewee - Clifford Rosen
It turned cloudy two years into the evaluation after approval. The FDA and the European Agency said, we want to do some post marketing studies and in the post marketing studies they said "Aha! you know there is something going on here, we don't really know what it is but there seems to be more anginal attacks and may be more heart attacks." This was really contrary to what everybody thought; they actually thought that this drug was going to protect against heart disease.
Interviewer - Chris Smith
So, how did the trials miss that? Because when you trial a drug, you are supposed to look into things like these kind of adverse outcomes.
Interviewee - Clifford Rosen
The sponsors chose patients that were not at high risk. They were obese and insulin resistant, but they didn't have diabetes, so their risk of heart disease was low, so when these events occurred, they were relatively uncommon. So even with large numbers of people, if you have relatively small numbers of events, that signal is going to be difficult to detect.
Interviewer - Chris Smith
So it's not really anyone's fault. The people that regulated..
Interviewee - Clifford Rosen
No! I don't think it was anyone's fault because theoretically and in the laboratory in cells it looked like this drug could do a lot of great things. We still see papers now coming out that, you treat cells with rosiglitazone and their vascular reactivity is less and they don't migrate and they don't build plaque and so you wonder and you say "Gee! You know, this is a good drug."
Interviewer - Chris Smith
But the worry is that, this kind of thing is going to really put a spanner in the works of the pharmaceutical sector because we are trying to encourage companies to develop new agents and make people better, but when you end up with an adverse outcome like this, Everyone flinches and it becomes so uneconomically viable for companies to develop new products, then what you do is create new versions of beta-blockers that don't do anything different than the ones we have for years.
Interviewee - Clifford Rosen
That's right. This is a big problem for industry. Because what it means really is you can't just say, haemoglobin A1c is the surrogate endpoint, it means better glucose control, that means better patient outcomes, that's what we've been operating under.
Interviewer - Chris Smith
So, what're we going to do? Are you going to completely advocate a rethink?
Interviewee - Clifford Rosen
Well, we have to have a rethink. We have to say, "Look we need a minimum of two years and we need a lot better safety data." One of the problems is that the data accumulated at all these sites, where the studies are being done, were not adjudicated; were not judged for some of these events. If a person had chest pain on the study what was that chest pain, how do you code it, what happened to that patient? This was not developed in the original trials and this is a real problem.
Interviewer - Chris Smith
Well obviously Clifford, we've got to sort this out, but the fact is who is going to pay for it because its already costing drug companies the average molecule that goes in test tube to patients costing 50 to 200 million dollars in 10 years, so who's going to pay for this in terms of finances and time?
Interviewee - Clifford Rosen
If the FDA is under-funded and that we need more resources, which everybody in the United States is talking about for the FDA, it shouldn't go into post marketing studies, where we just collect data, but it should go into helping to do some of these phase-III trials where safety is a huge issue.
Interviewer - Chris Smith
So what you are saying is that the companies can focus on making the agents and governments and politicians can focus on making sure they are safe.
Interviewee - Clifford Rosen
Yeah!
Interviewer - Chris Smith
Do you think that's likely to happen, because the budget will be absolutely monumental?
Interviewee - Clifford Rosen
I don't think it's likely to happen but things are changing. Already this has had some impact and people are rethinking. There is a letter coming out next week in the New England Journal by the FDA and they've already got one drug that has great efficacy for diabetes but they are doing more phase-III trials for safety and this is what we should be doing. I think the emphasis again should be both, efficacy and safety with patient outcomes, the final arbitrator.
Interviewer - Chris Smith
Cliff Rosen, he's at the St. Joseph Hospital in Bangor, Maine. In a second, how penguins are fouling up the Antarctic, food fraud, and a psychedelic cure for headaches. But first James, lead in paint has been big news recently with millions of toys being withdrawn from sales which is a health farce, but why put lead in paint anyway?
Interviewee - James Mitchelle Crow
Lead paint was a very popular paint in the first half of last century, before people realized, just how toxic it was, because as well as a giving a nice colour to the paint, it also had all sorts of other really quite nice properties.
Interviewer - Chris Smith
Do you actually have to eat it to get poisoned by it? Is it okay as long as you leave it alone?
Interviewee - James Mitchelle Crow
Well eating it, is a particularly bad thing to do, but you can also ingest it by breathing in the dust for example. There is a lot of advice out there for people renovating old houses that might have had lead paint still on.
Interviewer - Chris Smith
Apart from just making the paint look a nice colour, whether any other benefits of putting the lead in, which is why it become so popular?
Interviewee - James Mitchelle Crow
Well yes, there certainly were. White lead is very water insoluble, so it gives a really durable water resistant layer, and also lead carbonate neutralizes the acidic decomposition products of the oils that make up the paint. That makes the paint much more durable and long lasting. And I mean it retains its kind of flexibility so it prevents the paint from cracking for a long period.
Interviewer - Chris Smith
So, if we no longer can use lead, because it's obviously banned because it's so toxic, what have people substituted instead to get the same chemical effects?
Interviewee - James Mitchelle Crow
The pigment that lead has been substituted with is titanium dioxide, which has the same kind of the pigment effects, but is incredibly safe. It's even used in things like food colouring and sun screen, so there is no toxic effects of that at all.
Interviewer - Chris Smith
Obviously the ban isn't very well enforced, worldwide though, is it? Because we've seen millions of toys everywhere in Britain being withdrawn because they came from China and this paint had been used. So some countries still using large amounts of lead paint, presumably they are?
Interviewee - James Mitchelle Crow
They shouldn't be, but it seems like they are. This particular case, Mattel which is the world's biggest toy maker house had to recall thousands of toys that were painted in China and this particular company used lead-based paint rather than the non-toxic paints that the company were supplied with, so certain factories in China are using it illegally, it would appear.
Interviewer - Chris Smith
Very worrying indeed! Also very worrying is the accumulation of nasty things in penguins, Mark, tell us about this.
Interviewee - Mark Peplow
You'd normally think that the Antarctic was this pristine area of snow. But unfortunately it's not quite as pristine as it ought to be. You find molecules that are called persistent organic pollutants, things like organic chlorine pesticides, brominated flame retardants. Now they are not all bad, I mean brominated flame retardants will cause the thing that stops your sulphur going up like a candle, if you drop a fag end on it, but of course they shouldn't really be accumulating in the Antarctic. The latest research on this is actually looking at how these materials get distributed in the Antarctic, how they get there in the first place and what happens to them once they are there? Now in the past, people just assume that these volatile compounds have drifted there, if you like, through atmospheric transports, but quite recently people came up with the idea that may be they are being transported there by migratory birds.
Interviewer - Chris Smith
Well, how much more concentrated are they in the Antarctic than one would expect by just looking at background levels elsewhere.
Interviewee - Mark Peplow
This is the thing, in the Antarctic, there's virtually nothing that can break them down at all, out in the fields, just outside the studio, for example, there is enough things that will slowly but surely erode these things away, if you like. There are bacteria that can break these things down slowly but surely. In the Antarctic, once they are there, they really do tend to stay there, that's why they are persistent organic pollutants. But this latest study by a group of researchers at the University of Antwerp in Belgium, have basically looked at the role of penguins down in the Antarctic. Now they are not migratory birds, they are down there for generations and hardly a place or two, so they were actually looking at colonies of penguins and seeing what effect they had on distributing these persistent organic pollutants and what they found was that in these colonies, the penguins poop and carcasses of the penguins that die there are absolutely riddled with this stuff. The finding, concentration stand to a hundred times in many cases, greater than so of other areas of the Antarctic.
Interviewer - Chris Smith
So where are the penguins getting them?
Interviewee - Mark Peplow
Well, the penguins are getting them basically they eat so many fish which have trace amounts of these chemicals and these chemicals basically stay in the penguin system and accumulate and accumulate and either through their poop or through their carcasses when they die, they create these hot spots, if you like, of these persistent organic pollutants in the Antarctic.
Interviewer - Chris Smith
Is there anything we can do to clean this up?
Interviewee - Mark Peplow
Well, that's a good question. All of these sorts of compounds are now pretty tightly controlled. They weren't 30 years ago. A variety of legislation has come in most recently some thing called REACH, which covers all of chemicals in Europe, that has really cut down on the amounts on these chemicals which are used in some cases, banned them altogether, because people had realized that there is this accumulation effects. So from one point of view the answer is time, over the course of 100 years, these things will disperse and because we are not putting more of them into the system, if you like, their levels should go down. In terms of active cleanup, I suspect that it's simply too remote and too cold to actually get down there with a shovel and beanbag, to actually clean this stuff up.
Interviewer - Chris Smith
Has anyone speculated about what the consequences could be of these accumulations, secondary to the penguins?
Interviewee - Mark Peplow
The higher up the food chain you go, the more likely you are to see this sort of accumulation. There is a similar effect in the Arctic, when you see polar bears, because they are right at the top of the food chain, it's the chief carnivores. They are eating all the other things which have eaten all the fish, which contain the pollutants. So in some cases, certainly in the case of polar bears, it has been shown to ultimately have problems. With the accumulation of these chemicals, it may be shortening their lifespan, we don't know if that's the case with the penguins, but one can imagine that if you do see these rising concentrations of these pollutant hotspots around their colonies, its probably not good news for them.
Interviewer - Chris Smith
Poop-lution on an unprecedented scale. Thanks Mark. And now food for thought or at least this will certainly make you think next time you buy something to eat in a supermarket, especially if it's expensive. Here's Peter Berry Ottaway.
Interviewee - Peter Barry Ottaway
Food fraud is an amazingly large problem worldwide in terms of commodities such as fruit juices, it runs into hundreds of millions of pounds, in some of the smaller ingredients, for use in small amounts but of very high value, it probably still runs into millions of pounds collectively.
Interviewer - Chris Smith
So it's a massive problem, not just in this country but internationally. So what sorts of things tend to be the targets of this kind of adulteration?
Interviewee - Peter Barry Ottaway
Most of the ingredients in foods are of very high value, so things like fish oils which we've been working on, some of the ingredients in the health food industry such as aloe vera have been the target for quite a bit of adulteration over the years and we go right into the main commodities such as the adulteration of rice with different and cheaper species, basmati rice for example.
Interviewer - Chris Smith
How do most of these cases of fraud come to light? How is it noticed in the first place that somewhere there's something is fishy about your cod liver oil, let's say?
Interviewee - Peter Barry Ottaway
Well, the cod liver oil is quite fascinating because after we cracked the problem and worked out what they were doing, I had a off-the-record comment from somebody from one of the Dutch Ministries of Trade who said, "Aw! That explains the problem we thought, was a computer problem. We had 300 tons of oil going into the refinery and appeared to be 500 tons coming out, which is the reverse of what one would normally expect.
Interviewer - Chris Smith
But how was it that you actually cracked that puzzle. How did you solve the problem?
Interviewee - Peter Barry Ottaway
We had suspicions for sometime relayed to us from various companies and it's very competitive business, very high value business. We had to be very careful how we went about it. It turned out that the people doing it were very clever. Fish oils and cod liver oil in particular have a particular fatty acid profile that's high in certain fatty acids and low in others, and they had managed to just get these within the normal limits and ranges. We finally cracked it by finding a route via the cells. These are steroid alcohols and they are found in both plants and animals. If you take a fish oil from a pure source you'll find it's about 95% cholesterol, which is the same form of cholesterols we have in human source, similar to what we have in humans. If you look at plant sterols then there is a whole range of these which you can identify by both technology such as in the chromatography and HPLC and these plant sterols shouldn't be in fish oils; however, we found that in some samples of fish oil we were suspicious of, plant sterols were comprising up to 55%, which brought the cholesterol level down to about 45-50%. We then had to prove that the fish couldn't have consumed the plant sterols by other means, and that includes feeding on plankton for example.
Interviewer - Chris Smith
So, how did you do that?
Interviewee - Peter Barry Ottaway
First of all, we had various ideas, which we had to disprove. One was that in the troller, cutting of the fish, they might have been cutting into the guts itself which will spill the plankton over the liver while it is being removed from the carcas. And this ended up with me having to fly to Northern Norway and getting on the troller, going up into way into the arctic circle to try and catch cod and then we cut it then, to cut the livers and put them into serial samples for expression of the oils when we got back to the Fish Research Institute.
Interviewer - Chris Smith
So these people back, who are the manufacturers who have been fraudulent, they were cutting the cod liver oil with plant synthetic oils. This is presumably what this story is telling you.
Interviewee - Peter Barry Ottaway
Yes, it was in fact, the intermediaries who were doing it. And they were probably taking lots and lots of money out of it. In fact at the end of the day, we found it was rapeseed oil, which is a very cheap plant oil and as soon as we started publishing the fact we discovered this the whole market cleaned out rather rapidly, which is what we tend to find.
Interviewer - Chris Smith
Sort of, a Domino effect?
Interviewee - Peter Barry Ottaway
Yeah.
Interviewer - Chris Smith
But what about other things because that's one particular example? You mentioned quite a few. It seems like this is quite widespread.
Interviewee - Peter Barry Ottaway
Oh Yes! One that we did a lot of work on was aloe vera which is a cactus plant, which tends to grow in arid areas; very expensive juice and gel, and is used in a number of health food products; it's also used in some toiletries, shaving creams, because of its wound-healing potential. At one point about 9 or 10 years ago, we found probably a third of the aloe vera products in the market in Europe had a degree of adulteration.
Interviewer - Chris Smith
Gosh! That's very high.
Interviewee - Peter Barry Ottaway
Credibly high.
Interviewer - Chris Smith
If you look at the Olympics, going back a number of years, you can see the effects of people doping and using drugs and things. Athletics has had to clean up its act, but that forced the people that were, let's say, a bit less willing to obey the rules to be even more cunning. So what we're going to see now, these food frauds does becoming even more cunning, working out clever ways to deceive people like you.
Interviewee - Peter Barry Ottaway
I always find it a challenge because those who are doing it, those who don't want to get caught early on are being very clever. They do analyze the chemistry of the products, they know how far they can go under normal techniques, what limitations of the analysis are and they make all the modifications so that it is very hard to actually prove it first time off. With the aloe vera we were wallowing around for a whil
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