January
Chemistry World Podcast - January 2007
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Brought to you by the Royal Society of Chemistry, the Chemistry World Podcast.
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Interviewer - Chris Smith
Hello Happy New Year and welcome to the Chemistry World podcast episode number 4 with Chemistry World's Editor Mark Peplow...
Interviewee -Mark Peplow
Hello!
Interviewer - Chris Smith
With science correspondents, Victoria Gill...
Interviewee -Victoria Gill
Hello!
Interviewer - Chris Smith
And Richard Van Noorden...
Interviewee - Richard Van Noorden
Hello!
Interviewer - Chris Smith
And with me Chris Smith. This month how there's a fortune in precious metals and concentrated ores lurking on the seabed.
Interviewee - Steve Scott
There's a lot of secrets in the deep ocean that we're just beginning to understand and one of these is the hot springs on the deep ocean floor that are spewing out fluids at temperatures as high as 420 degrees centigrade and in this fluids are dissolved metals, iron, copper, zinc.
Interviewer - Chris Smith
Steve Scott will be exploring the feasibility of harvesting hydrothermal vents very shortly. Also, the washing machine that's got the U.S.'s Environmental Protection Agency - the EPA, all in a spin.
Interviewee - Richard Van Noorden
The saga begins when a Samsung washing machine which released silver ions into your clothes to kill bacteria was classed as a pesticide by the EPA, these silver ions could accumulate in wastewater treatment plants, might possibly kill bacteria that were meant to treat the wastewater.
Interviewer - Chris Smith
And deferring to death row - how a trial to size up the risk of organophosphate exposure amongst farmers could be back on track? Or is it?
Interviewee - Sarah McKenzie-Ross
Although DEFRA have agreed to continue funding us, though it states that, we have to write a report finding an alternative control group from the one that we originally suggested. I am making a very strong argument for why it is feasible.
Interviewer - Chris Smith
That's all on the way, but first cast your mind back to the Christmas festivities and Mary's chemical conundrum from the December Chemistry World podcast.
Interviewee - Mary
When Christmas presents were invented what made them go bang?
Interviewer - Chris Smith
Any ideas? Well keep listening to find out if you're right later in this program. Now first this week Mark is getting straight to the heart of the matter with a look at a way to use cardiac cells to pump fluids around labs on chips.
Interviewee - Mark Peplow
Yeah that's right. Normally when you have miniaturized, labs-on-chips, you use conventional electrically powered pumps to move fluid around tiny channel to make chemicals react together for example. A Japanese team have managed to replace those electric pumps with heart cells, so this device is essentially a bowl of silicone polymer and on either side of it you have a little bundle of heart cells. The whole thing is only about 5 mm in diameter. They set little Teflon tubes in either side of this squeezy bowl and they found that as long as they keep feeding nutrients to the heart cells, the heart cells keep beating and they can go for about 5 days continuously pumping fluid through this bowl.
Interviewer - Chris Smith
So, as the heart cell or group of cells contracts, then this squashes the bowl and therefore squeezes the tubes.
Interviewee - Mark Peplow
That's right. Yeah. Now its one of the applications could be for moving liquids around these sorts of lab-on-a-chip devices. Looking further into the future, the researchers are suggesting it may be useful in medical implants. Normally if you have a pump working in your body, and it will need a battery with it and these need replacing. If you could have a system, where it is relying on the heart cells to actually do the squeezing of the bowl to do the pumping, in theory they could last much longer and take up a lot less room as well.
Interviewer - Chris Smith
But if you're using this kind of a near patient monitor system just to have a lab-on-a-chip, then really the size constraint is less important, so is it worth the practical application to do this with these cells?
Interviewee - Mark Peplow
Well, one of the things that people working on these labs-on-chips are trying to do is to try and bundle all things that would normally get in a laboratory, all the huge big equipment and try and get that all on one postage stamp sized chip effectively. Now it is all very well having that, but if you need a huge power device or a pumping mechanism stocked to the side, you lose the benefits of that miniaturization. So, this is just one more way that they are trying to cramp everything they need onto the size of a postage stamp.
Interviewer - Chris Smith
A piece of technology almost or just in the space of one heartbeat, but talking about cancer now and the 'morning after pill' allegedly can prevent breast cancer, Victoria
Interviewee - Victoria Gill
Yeah that's right. The active ingredient mifepristone, the active ingredient in the 'morning after pill' can prevent breast cancer development in quite a specific group of patients, patients with a susceptibility gene mutation in a gene called BRACA 1 and these are really small group of women at the moment, but these patients have to go through a very traumatic experience when they are diagnosed with this particular mutation and there is so high risk if they have this mutation. They often undergo double mastectomies just to prevent themselves developing these cancers.
Interviewer - Chris Smith
So how did researchers find that taking the 'morning after pill' might actually offset that risk set by that gene?
Interviewee - Victoria Gill
Well, the crucial component is progesterone and progesterone is a hormone that's very important in pregnancy and mifepristone is a progesterone antagonist, which is how it works to cause basically a miniature abortion when you take the 'morning after pill' as an emergency contraceptive. Now, the BRACA 1 gene produces a protein which degrades progesterone receptors. If you degrade these progesterone receptors in this tumour mammary cells then the progesterone contact upon them to cause the cells to proliferate. So it prevents cancer developing.
Interviewer - Chris Smith
And are they planning to do some clinical trials because this sounds like a very important step forward for this subgroup of patients who carry these BRACA mutations.
Interviewee - Victoria Gill
It is, but at the moment, this is just work that's been done in the lab on mice with induced mammary tumours, so this comes from the University of California, so it's early stages now, but yeah, that will be the next step.
Interviewer - Chris Smith
I guess it will be interesting too because the BRACA mutations aren't just associated with breast cancer because they lead people to have an increased risks of things like ovarian cancer as well.
Interviewee - Victoria Gill
Yeah exactly! So these are all things that can be investigated and obviously when you are dealing with an already approved drug, it's something that can be taken forward quite quickly.
Interviewer - Chris Smith
Heartening news! Thanks Victoria. And now we're off to the bottom of the sea with University of Toronto's Steve Scott, who is searching for buried treasure. Now it's not the stuff you'd associate with pirates, but in fact concentrated deposits of ores that might be very cheap to exploit.
Interviewee - Steve Scott
The deep sea occupies a big part of our planet. The oceans are 71% of our planet and the deep sea is about 80% of that, so there's a lot of secrets in the deep ocean that we're just beginning to understand and one of these is the hot springs on the deep ocean floor that are spewing out fluids at temperatures as high as 420 degrees centigrade and in these fluids are dissolved metals, iron, but more interestingly, economically at least, copper, zinc, lead, silver, and gold that are precipitating around these hot springs on the sea floor and building up towering chimneys as much as 40 meters high that of course are unstable and they eventually fall over and produce accumulations of chimneys that grow into mounds and produce, what for all intents and purposes, are ore deposits on the ocean floor.
Interviewer - Chris Smith
How abundant are those ores, Steve? How much of them, is down there?
Interviewee - Steve Scott
Well there's about 350 sites that we know about now and in total thousands of these so called hydrothermal vents or hot springs. Some are very small, some of it would fit in somebody's dining room; others are quite large. For example, the ones in the Bismarck Sea off the East Coast of Papua New Guinea, some of those deposits measure a few hundred meters in diameter.
Interviewer - Chris Smith
So are they actually exploitable because some people have suggested that these particular ore deposits are much more enriched than all that we could get out of the ground normally, in the normal mine or something, and therefore they might actually be worth the sort of pillaging, to get the goodness out.
Interviewee - Steve Scott
Yeah, I definitely think they are exploitable, at least ones in the Manus Basin, exactly a site that I discovered back in the '90s, our own sampling plus the much more detailed sampling by mining exploration group called Nautilus Minerals has verified that this is incredibly rich. Now they took a 15-ton bulk sample out of one of the deposits and it averaged something like 5.2% copper and 6.6 grams per ton of gold. Now a typical mine of this type on land, that are in volcanic rocks, which we have around the world in various places, lots of them in Canada, they would average may be 2 to 4% copper and may be a gram or two a ton of gold.
Interviewer - Chris Smith
Is it actually economically viable to recover though because whilst it may be richer, of course, you've got the added problem of a lot of seawater above you?
Interviewee - Steve Scott
Yeah, you've got a lot of seawater. The Manus Basin site, it's in 1600 to 1700 meters of water, but you know, there are mines on land that are down 3000 meters, for example in Timmons, the Kidd Creek mine here in Canada and it's a whole lot easier to go down through a couple of thousand meters of water than a couple of thousand meters of rock. All you have to do is put a pipe down there, whereas on land you've got to do an awful lot of blasting and drilling that's very expensive to do.
Interviewer - Chris Smith
Can you actually do a sort of environmental calculation to work out which is actually better for the planet in the long run? Is it better to go down to these pristine marine environments and exploit those or is it better to do the drilling and blasting that you mentioned?
Interviewee - Steve Scott
I personally think that in fact the ocean mining will be less environmental problem than mining on land and it's not a question of how to(UNCLEAR 9:44) the mine, because no one will accept that. On land, you have to dig big holes in the ground. If you have an open cast mine, you've got to remove awful lot of barren rock to get out the ore, you know, may be for every ton of ore you might have to remove 5 or 10 tons of barren rock and you have to put that rock somewhere and you will leave a big hole behind the ground and when it rains it produces acids from the breakdown of the iron sulphide, makes sulphuric acid and creates acid mine drainage, which is a big problem. In fact those are three biggest problems of mining on land. In the oceans, you won't generate acid drainage, because the oceans are alkaline. So you just simply don't generate the acids, there'll be no big holes in the sea beds because these things are sitting like bumps on the sea floor. You're going to remove that bump. It's referred to as surgical mining. You take just the ore and so you are not removing any waste rock. So, the three biggest problems for mining on land don't exist in the oceans. The other environmental side of this is the biological side and there it's different. You know on land, you're going destroy some trees, may be a few animals and so forth. In the deep ocean, there are ecosystems that are not terribly well understood and I don't think anybody including the companies who want to exploit these things would want to be labelled as the destroyers of the only living example of something and as a result, that is the one company called Nautilus Minerals, that is exploiting or intending to exploit the Manus Basin site in 2009, they have been actually for many month now carrying on a baseline environmental study using Ph.D. biologists to do it.
Interviewer - Chris Smith
Steve Scott and sticking with that watery theme, a washing machine's got itself into hot water of nanoregulations, Richard!
Interviewee - Richard Van Noorden
Well apparently Chris, yes. The US Environmental Protection Agency - the EPA, were trumpeted as the first ever regulation on nanoparticles and it was all down to a washing machine. The saga begins when a Samsung washing machine, which released silver ions into your clothes to kill bacteria was classed as a pesticide by the EPA because possibly these silver ions could get out, could accumulate in waste water treatment plants, might possibly kill bacteria that were meant to treat the waste water.
Interviewer - Chris Smith
But people have been using silver particles for thousands of years. The Egyptians sterilized their water with it, didn't they?
Interviewee - Richard Van Noorden
That's right, but we know a bit more, know about the toxicity of the silver dependent on its environmental concentrations. So, all the EPA wanted to know was, you know, what is the exposure of silver, but that got turned into a regulation of nanoparticles because Samsung were marketing their washing machine as containing nano silver. Now the EPA can't possible really regulate nanoparticles because they can't ask questions to Samsung about the nano aspects -- the aspects of the size and shape of the particles rather than just asking about the silver aspects and this is a general problem. There really isn't enough research into the basic health and safety aspects of nanoparticles, to say, what does a nanoparticle do, that a particle of silver that's larger doesn't.
Interviewer - Chris Smith
So we're looking at having rather like we've got the biohazard side at the moment, there will be something similar constructive for nano hazards and you've to stamp it on absolutely everything all the time.
Interviewee - Richard Van Noorden
Well unfortunately a nano has its sign with probably being entirely meaningless and that's probably why we need more research into the different classes of nanoparticles and their effects. Many people have suggested that both US and the UK need to invest a lot more money into health and safety research and a lot lesser proportion into what the nanoparticles can do.
Interviewer - Chris Smith
So, at the moment, do we actually have any of that in place or people just generating nanoparticles willy-nilly for absolutely everything, I mean they're in socks - on the odour-eating socks, are in various clothes, they are in things to keep fridges sterile. Do we actually know what the consequences are and are there any mechanisms in place to check them?
Interviewee - Richard Van Noorden
Well at the moment, all the research that is being done. The US are throwing around 40 million dollars this year into research groups independently looking at different aspects of nanoparticles. Andrew Maynard the director of the projects on emerging nanotechnologies in the US told us that that was rather haphazard; there was no overall strategy. Well the UK has got a lot of high-powered groups together, the Royal Academy of Engineering, Royal Society, but that's all rather slow. So they're taking a much more integrated approach but they may never get to the end. But when we actually have our first nanoparticle regulation, in Berkeley in the US, they have a small municipal regulation now that anyone working on nanoparticles has to survey the literature and report their nanoparticle exposures and so on, but that are very much depends on what literature there is and at the moment there isn't enough.
Interviewer - Chris Smith
And the fate of the washing machine?
Interviewee - Richard Van Noorden
As yet undecided. Samsung say they will cooperate with the EPA.
Interviewer - Chris Smith
Thanks Richard. And we'll be returning to the safety of nanoparticles, this time in the form of air pollution, later on in the podcast. But first, here's Sue Ferns from Prospect, the union that represents public sector scientists, in other words, scientists who work on issues like food safety, climate change, pollution, and biodiversity. She's very worried that the erosion of funding and a poor career structure are threatening to jeopardize this key part of our infrastructure.
Interviewee - Sue Ferns
The core problem is that really nobody in government is taking a strategic overview of public sector science, so we've got this very good science going and we wouldn't want to say otherwise and although government have invested in science base, inside, government departments are crushing back on their science budgets, the funding that is coming through some of it is going into new facilities which is fantastic but those facilities are very expensive and what we're concerned about is there doesn't seem to be the same investment going through into the scientific staff which of course are equally as important as having good facilities.
Interviewer - Chris Smith
I suppose the senate could argue that one should let market forces drive what's happening in the scientific world though, shouldn't we?
Interviewee - Sue Ferns
Well, I think to some extent market forces do drive some science; however, what we're concerned about is that the science that will simply won't be done if it is left to market forces. In the kind of science I'm talking about, there is long-term data gathering, for example, for climate change monitoring, also science in support of public policy and also we do know from experiences that BSE and the Mad cow disease crisis and that the people in the front line in those times are public sector scientists and the government needs to be able to call on them very quickly.
Interviewer - Chris Smith
The figures don't make exciting reading, do they? I mean, in fact they look really rather scary when your own study shows that 40% of scientists you asked said they will or might quit science.
Interviewee - Sue Ferns
Yes, well our study also showed however that with that three-quarters of them actually wanted to stay in science, though many of them are being forced down either due to retirement or redundancy because of budget pressures, but other scientists are coming in fast; very enthusiastic and young scientists which is what our survey seems to show, after they get on their second or third fixed term contract they see there is no great progression, they very quickly get upset and they realize that they can take their talents else where
Interviewer - Chris Smith
But even more worrying Sue, it must surely be the fact that the government doesn't even have any clue how many scientists at least it would appear they actually employ?
Interviewee - Sue Ferns
Absolutely, they doesn't have the clue because we've asked them and we've asked questions in parliament and they simply don't know that. They don't know how many scientists they employ, they don't know what their scientific capability is and first that's hugely worrying not just for today, but looking ahead in terms of the scientific challenges the UK is likely to face, government can't actually say with any confidence that it has the scientists to meet those challenges.
Interviewer - Chris Smith
But what do you think it is actually going to take in the workplace to convince these 40%, 4 people in every 10, who want to quit? What's going to convince them to stay?
Interviewee - Sue Ferns
What's going to convince them to stay is not having to spend one day for every working week, bidding for funding, what would convince them to stay is if they had core funding and not have to compete for funding all the time if they could look ahead with some certainty over five years rather than 18 months or so on, they need to have basic pay, they need to have basic career prospects, they need to be treated like the professionals they are.
Interviewer - Chris Smith
Sue Ferns from Prospect and you can read Sue's article about the problem in this month's Chemistry World. On the way, will new chemical legislation make Europe a safer place or just less viable for business and out of sights and out of mind or not; we will be taking a look on how nanoparticles in vehicle exhaust fumes may be a previously overlooked threat to our health. But first Victoria, bacteria are now having scientists to target tumours more effectively with anti-cancer drugs.
Interviewee - Victoria Gill
Exactly! A new meaning to friendly bacteria. This particularly exciting bacteria has a protein within it that can break open little packages that contain cancer-fighting drugs and because one of the problems with chemotherapy is, although it is very effective at fighting cancer it also causes a lot of collateral damage and is equally damaging to healthy tissue, so one of the things that cancer researchers have been doing is finding ways to package it to protect healthy tissue and deliver it specifically to tumours and one of the things they can do to do that is package it inside liposomes, which are lipid membranes surrounded with water-filled capsules that you can put a soluble drug inside. But you then need to get into these little packages and deliver the drug at the site of the tumour. Now this is where the bacteria comes in because the bacteria Clostridium novyi that they have used, contains a protein that lyses or opens up these liposomes but the really exciting thing about this particular Clostridium is that it selectively infects tumours, because it likes the anaerobic conditions of tumours, tumours proliferate really quickly and they don't form a good health vasculature; so they're very hypoxic and this particular bacteria likes to live in tumours, so if you inject the bacterial spores at the same time as injecting these liposome-encapsulated drugs, then they will pop open but only within the tumours.
Interviewer - Chris Smith
Is this in animals or have they've got this in people yet?
Interviewee - Victoria Gill
Well it is moving pretty quickly, but at the moment this data, these results come from mice, they have induced colon tumours and they've managed to eradicate pretty much all of the tumours, it was something like 90% of these tumours were eradicated. They then wanted to look at how they were going to take this to the next stage without just injecting humans with bacteria, because there are a lot of side effects associated with injecting bacterial spores into people, you get..
Interviewer - Chris Smith
Can't see many people wanting to be injected with Clostridium, given that same family has got the bug that causes tetanus; now the bug that causes gas gangrene; and one that causes botulism.
Interviewee - Victoria Gill
Yeah exactly, you're going to get a lot of nasty side effects that is pretty much guaranteed. So what they've managed to do is that they have isolated the protein that is doing the lysing, what they found is that there is a new protein that they have not seen before, it is a new enzyme and they have termed it liposomase because it breaks open liposomes, and so what they can do now is that they can take this liposomase and eradicate the need for these nasty bacterial spores that might cause all sorts of problems in people and use this to break open liposome encapsulated drugs.
Interviewer - Chris Smith
Thanks Victoria. This is Chemistry World podcast with me, Chris Smith. Now if you've been listening to previous editions of this program, you probably will recall our report on the suspension of a study that DEFRA commissioned into the possible link between organophosphate-containing pesticides and ill health amongst farmers who use them. The study began in 2003, but it has encountered a number of problems tracking down a suitable control group of individuals. The team have come up with a number of possibilities, but they've all been rejected by the VMD or Veterinary Medical Directors. DEFRA have now allowed the study to continue but the problem is far from solved. UCL researcher Sarah McKenzie-Ross is leading this study.
Interviewee - Sarah McKenzie-Ross
We're trying to do a study which is investigating whether low level exposure to organophosphate pesticide is associated with ill health and as a part of the study we wanted to recruit farmers who have worked with sheep dip over the years but also we wanted what we refer to as a control group which is a group of people who look very similar like the farmers but haven't been exposed to pesticides. Initially we hoped that we could find some sort of farming population but this turned out to be impossible because it seems that all farmers even organic farmers have at some point in the past used pesticides, so we have to look at using alternative occupational group and we made several suggestions to DEFRA as to what might constitute the suitable comparison or control group.
Interviewer - Chris Smith
And they weren't happy with that?
Interviewee - Sarah McKenzie-Ross
Well DEFRA also thought that the rural police might make a feasible comparison group, but when DEFRA asked advice from a scientific committee within the VMD, the scientific committee had very strong views on this issue and felt that the police wouldn't make a suitable control group.
Interviewer - Chris Smith
And did they volunteer a more suitable alternative.
Interviewee - Sarah McKenzie-Ross
No they didn't give us any alternatives. We came up with 12 possibilities in total and it's quite easy to find faults with any one of the suggestions we made and certainly the VMD had no difficulty finding fault with things, but they weren't helpful in helping us find an alternative.
Interviewer - Chris Smith
And have you now resolved that problem?
Interviewee - Sarah McKenzie-Ross
No we haven't done, although DEFRA have agreed to continue funding us they've said that we have to write report finding an alternative control group from the one that we originally suggested and making a very strong argument for why it is feasible and I don't know what they would do with that information once we've given it to them -- presumably it will go back to the VMD and may well be criticized again.
Interviewer - Chris Smith
Have there been any major consequences for your study as it has progressed because it has been ongoing throughout this, hasn't it? What have been the impacts of this on the actual progression of the study?
Interviewee - Sarah McKenzie-Ross
There are two main impacts, firstly we wanted to start testing comparison subjects at the same time with farmers, so when farmers were busy we could get on with testing comparison subjects, but that hasn't been impossible to have them agree to who the comparison subjects will be. So all in all what will remain is that this project will no doubt have to ask for an extension in order to be completed, so that's one outcome. The second more worrying outcome has been that a number of farmers have heard that our funding is underswept because of this issue and so when they've been phoned up and asked to take part in the study, they've said to my researcher, Oh! What's the point, they're probably going to pull the funding on your study, why should I bother taking part, so we have lost participants.
Interviewer - Chris Smith
And your message to DEFRA of the back of your experience would be what?
Interviewee - Sarah McKenzie-Ross
The main issue in terms of control groups is that, of course, there isn't a farming population that has not been exposed, you have to use an alternative occupational group and any occupational group you can criticize on some level because they don't look exactly like farmers, but the main important point is that they only need to be matched on variables that might affect the measures that we are using, so really we just need to find a group of people who have of similar age, live in a rural location, similar gender and similar level of intelligence to the farmers that we're testing; those are the only things that matter. It doesn't really matter whether they're police or postal workers or shopkeepers.
Interviewer - Chris Smith
Sarah McKenzie-Ross and I am sure we'll be returning to that story sometime in the future. Now to the safety of chemicals used in Europe. REACH is the acronym, but what does it stand for and what does it mean for industry, Mark?
Interviewee - Mark Peplow
REACH is the largest and most complicated piece of legislation that's ever come out of the European Union. It also stands for the registration, evaluation, authorization, and restriction of chemicals. Now that (UNCLEAR 26:14)honestly it is important and essentially quite interesting. Up until now we have had this hotchpotch of about 40 different acts, which has overseen how chemicals manufacturers can move around and sell their chemicals, some are more dangerous than others, bad for the environment, bad for health, but this is really not been terribly joined up and extended to over-regulate for newer compounds, but not pay enough attention to those that had been in use for decades.
Interviewer - Chris Smith
Which may be equally as destructive?
Interviewee - Mark Peplow
Which may be equally as destructive, who knows? And the lack of data on those older compounds has been one of the things that has been driving REACH. European politicians have been debating about this for more than 3 years with a lot of lobbying going on for both the chemical industry and the environmental campaigners and trying to work out an alternative to the existing system and what they have come up with is REACH. Essentially what it's doing is putting the onus on determining how safe chemicals are back onto the chemical industry themselves, so rather than government agencies going out and saying, let's test these chemicals to see whether they're bad or good, it is up to the industry to provide that safety data.
Interviewer - Chris Smith
But to do that you need massive great epidemiological study, you need thousands of study participants and you need really good records, you need very careful evaluation to work out over a period of time whether something does have nasty side effects, so is that doable by average industry?
Interviewee - Mark Peplow
Well that's right, one of the issues is, of course, how do you assume whether something is safe enough, what level do you cut off at, do you just do some animal studies or do you look at the effect on population of 60,000 or more and in a sense what's going to happen? Is it depends on what people already know about the risks of these chemicals.
Interviewer - Chris Smith
Is that what they're really expecting companies to do, to commission animal studies and then human trials to see if this average chemical that they want to put in their plastic bottles is safe?
Interviewee - Mark Peplow
One other problem with the existing system is that lot of this data actually already exists. It's just because of the proprietary nature, if you like, the fact that this is an all intellectual property and there's not been awful lot of data sharing, so one of the things that REACH is trying to do is to ensure that, that epidemiological data, the animal study data gets shared around freely between industries so that there is less duplication, ultimately although you expect there to be a small rise in animal testing over the first few years of REACH, ultimately they hope that this data sharing will severely reduce the amount of animal testing that needs to go on.
Interviewer - Chris Smith
On the other hand if they might restrict their claim here too much, won't you see people to a country where REACH does not extend its reach, if you like, and therefore people will go abroad and do their work?
Interviewee - Mark Peplow
A lot of industrial lobbyists have said that this will be the outcome. It's coming from actually the industry say, that regulations are far too stringent, environmentalists say, that it does not go nearly far enough, but one of the argument says, as you said that, if you set up too much regulation where it is actually very expensive to get a chemical approved for sale or use within the EU, because this will cover to some extent imports of chemical into Europe for use as well from outside of the EU, then yeah, the fear is among industry that investors looking to put capital into a new manufacturing plant, for example, will say, well actually it's going to be simply easier for us to make that plant in China or India, where the regulations are perhaps less stringent. To be honest only time will tell. REACH is being phased in over the next 11 years up until 2017, so it's going to be at least a decade before the full impact of this is felt.
Interviewer - Chris Smith
Thanks Mark, over to the pharmaceutical industry now and the collapse of the top-tipped clinical trial. Derek Lowe is medicinal chemist and he is also the Editor of the drug discovery web site 'In the Pipeline'.
Interviewee - Derek Lowe
What I've written about is one of the worst clinical failures to occur in the drug industry in many years, which is quite a competition because we've had some especially bad ones over the last few years, but this was one of the most anticipated drug launches especially by Pfizer because they're trying to replace the biggest selling drug ever, Lipitor, and they had what they thought could have been new a record holder for the biggest selling drug ever. On Thursday of the week, they came out and talked about how great things were going and on Saturday the drug was gone.
Interviewer - Chris Smith
What actually is that drug? How does it work and why is it thought to be such a prize chalice to the drug industry.
Interviewee - Derek Lowe
Well the drug is called torcetrapib and the idea was that this would raise HDL, the so-called good cholesterol. Lipitor and the other statins all lower LDL, the bad cholesterol so this was a natural companion piece. There are number of other companies that had been working on drugs to raise HDL, but torcetrapib was by far the farthest along and was going to be the proof of concept for the entire area.
Interviewer - Chris Smith
And it was in phase III, wasn't it?
Interviewee - Derek Lowe
It was.
Interviewer - Chris Smith
And what actually went wrong and why did they subsequently decide to withdraw it?
Interviewee - Derek Lowe
Well, the earlier studies had looked good. They showed that the mechanism seemed to be working, HDL was coming up and there was one worry though, there was a slight rise in blood pressure in the patients getting the drug, so that was a cloud on the horizon, but what happened was Pfizer expanded to a larger trial as you do in phase III and what they found was that the death rate in the drug treatment group was significantly higher than the placebo group and of course that immediately put the brakes on the entire project.
Interviewer - Chris Smith
Pfizer aren't the only company that are producing drugs which are targeted at this particular enzyme, you know, CETP, the cholesterol ester transfer protein, other companies are too, so does this put the kibosh also on other companies then?
Interviewee - Derek Lowe
They would certainly like to know that Roche, for example, has a compound they licensed in from Japan from JTT and that is the second farthest along and Merck is understood to be working in the area as well. The complication is that these three compounds may be acting on CETP slightly differently, so the big question is, is it a mechanistic problem, anything you do to CETP will cause this or can you hit CETP in a slightly different way and honestly no one knows yet and I can tell you, I'm sure that people at Roche and Merck are just holding their breath trying to find out.
Interviewer - Chris Smith
And you put it very well when you say it is like making a living by staggering blindly around in a casino waving a wad of cash in one hand and a fistful of test tubes in the other, that must be how they feel, because they have got no option now but to go ahead and explore the compounds because they've taken it so far and they can't wind it up, because the outcome actually might be okay?
Interviewee - Derek Lowe
Exactly! It's like Macbeth you know, 'should I step no more returning were as tedious as go o'er,' they really have no choice. It is quite an industry to make a living in, I can tell you.
Interviewer - Chris Smith
From a clinical point of view, what do you think the ramifications of the failure have been?
Interviewee - Derek Lowe
Well, they've really made people think about HDL. Clearly the idea that just raising HDL is across the border a good thing is too simplistic. We should have learned this lesson before, because every time we go into the clinic we find out things aren't as simple as we thought, but the human lipid profile has just been getting more and more difficult to understand whatever the advance we make in the field and now it's HDL's turn, there is something else going on there that we have to figure out.
Interviewer - Chris Smith
Derek Lowe commenting on the collapse of torcetrapib trial which was Pfizer's drug test to raise HDL the good cholesterol in the blood. Right back to nanoparticles now and the question on everyone's lips is what's coming out of your exhaust pipe, Richard?
Interviewee - Richard Van Noorden
Well Chris, it refers to quite an interesting study done by researchers at Leeds. They went to a roadside in Leeds and they measured the particle concentrations in the air in rush-hour traffic and interestingly they found that those particles were a lot smaller then you might have thought; in fact the number of particles in the air was really dominated by small nanoparticles.
Interviewer - Chris Smith
Didn't we know this already, I mean, we know that diesel was being highly efficient as a fuel is actually quite savage for your lungs, isn't it?
Interviewee - Richard Van Noorden
Yeah, we did know this, but we tend to regulate what is called PM10's, particles of around 10 microns or less. Nanoparticles were lot smaller than that and at the moment legislation on air quality tends to go on these, sort of, massive particles that you find in the air, but the Leeds researchers point out that the nanoparticles don't make up much mass in the air, they are very light may be one to 20%, but they make up 90% of the volume of particle in air, they've got such a large surface area and the nanoparticles are the ones that might do damage even more than the micron-sized particles.
Interviewer - Chris Smith
Had we just not looked for them before then?
Interviewee - Richard Van Noorden
I don't think the extents of the amounts of nanoparticles may have been appreciated before -- this is a very preliminary study.
Interviewer - Chris Smith
And what do they say the bottom line is? Do they think these things could harm health?
Interviewee - Richard Van Noorden
Well nanoparticles can actually get into your lung, penetrate deeply and crossover possibly into your bloodstream which micron-size particles might not be able to, so there is that danger but we simply don't really have the safety research.
Interviewer - Chris Smith
So you're urging more of a look-see to find out what the consequences are?
Interviewee - Richard Van Noorden
That's right, yeah! The Leeds researchers want more details into the consequences, more details on what's in our air and possibly a change in the way we think about the mass or the volume of particles in the air.
Interviewer - Chris Smith
Because people who have looked in the past at the stickiness of blood on high pollution days and we find the heart attacks go up on days when air pollution and air quality is bad, this could be a part of that?
Interviewee - Richard Van Noorden
That's right, it could be. They did actually find that when they looked at the particles in the air during the day, during the rush hour afternoon, the vehicle emissions were dominated by larger particles, but in the morning when the sun was shining they found that nanoparticles were actually made photolysis and were much smaller. So, actually depending on different times of the day and different formation mechanisms, you can actually get different sizes of particles in the air. None of this really appreciated before.
Interviewer - Chris Smith
Thanks Richard and now back to Mary's question, which was when Christmas crackers were invented, what made them go bang? To explode the story for us, here is Edinburgh University's Colin Pulham.
Interviewee - Colin Pulham
There is no Christmas cracker complete with a loud bang. It was developed by London-based confectioner called Tom Smith in 1860. It's actually proved quite difficult to predict on the precise nature of the chemical mixture used in the early crackers; however, one source suggested saltpetre or potassium nitrate were used. Now potassium nitrate is an oxidizing agent that is used in gunpowder and when combined with a fuel such as sulphur, carbon or sugar, it provided oxygen necessary for rapid combustion of these fuels. This results in rapid release of gases such as sulphur dioxide, carbon dioxide and steam and hence the loud bang. Another possibility is that Tom used a mixture based on a type of match commonly used at that time, known as Lucifers. These matches contain potassium chlorate and antimony sulphide mixed with a little gum and to be ignited by friction by rubbing against sand paper, there was also reportedly a loud bang when struck. In this reaction, potassium chlorate act as an oxidizing agent and the products of the reaction are sulphur dioxide, potassium chloride and antimony monoxide. Modern day crackers generally contain very small amounts called silver fulminate, formula AgOCN. Silver fulminate is termed an endothermic compound and is also very sensitive to shock or friction. When set off in a cracker, it decomposes rapidly to giver silver, gaseous nitrogen and oxides of carbon. Silver fulminate is also found in so called throw-down snaps. These are the twist of paper containing grit coated with silver fulminate. When these are thrown at hard surfaces, friction sets off the fulminate and we get a loud bang.
Interviewer - Chris Smith
So, it all started with the confectionary trade. I wonder if that's where the saying, "business is booming" comes from. We've got a painful question to tackle this month, it's from Petro.
Interviewee - Petro
I would just like to know why bruises are the colour they are and why do they change colour over time?
Interviewer - Chris Smith
So if you can help us with that then please use the contact details at the bottom of the page and you can also use that address if you'd like to send us any feedback. That's it for this month's edition, which was produced and presented by me Chris Smith with by Chemistry World's editor, Mark Peplow and science correspondents, Victoria Gill and Richard Van Noorden. I'll be back next month, until then Good Bye!
