September

Chemistry World Podcast - September 2012

1:08- Will the Curiosity rover be able to find life on Mars?

4:34- Fluorine - the most reactive element - has been found in nature

7:38- Ruth Mcnerney discusses the challenges in detecting and treating tuberculosis

15:36- Can a skin cream deliver insulin and replace daily injections?

18:08- Magnetic bonds predicted to exist - but only in the magnetic fields around neutron stars

21:03- Paul Workman, Chemistry World entrepreneur of the year 2012

29:22- Summer storms drive ozone depletion

33:18- A cyborg jellyfish that should help test heart drugs

36:11- Trivia: If the sky on Mars is red, what colour is the sunset?

(Promo)

Brought to you by the Royal Society of Chemistry, this is the Chemistry World Podcast.

(End Promo)

Interviewer - Chris Smith 

This month, the disease that affects about a third of the world's population and is becoming resistant to all of the agents that we can throw at it. 

Interviewee - Ruth McNerney

Once you're resistant to the second line drugs then it's very, very difficult to treat.  We've even seen cases now being reported where what we're calling total drug resistance where the bacteria is resistant to every single drug that's being tested on them so far.

Interviewer - Chris Smith 

Plus scientists find fluorine seeping out of rocks in Germany, cyborg jelly fish and sunsets on Mars, we ask what colour are they?

(Promo)

The Chemistry World podcast is brought to you by the Royal Society of Chemistry, look us up online at chemistry world dot org.

(End Promo)

Interviewer - Chris Smith 

Hello, welcome to September's Chemistry World podcast.  I'm Chris Smith and with me this month, due to spill out some of the biggest and brightest breakthroughs in chemistries for you, our Philip Robinson, Elinor Richards and Neil Withers.  We kick off this month on Mars.  There's been much fanfare about Curiosity, the rover that's there, but some scientists are saying this is destined to fail to find life before it even got started.  Phil.

(1:08 - Will the Curiosity rover be able to find life on Mars?)

Interviewee - Philip Robinson

Back at the beginning of August, NASA landed a rover on the surface of Mars.  Now that it's there, it's going about the job that it was designed to do which is analyzing the earth, the Martian surface and atmosphere.  One of the things that it's going to be looking for is the presence of organic molecules. 

Interviewer - Chris Smith 

With the idea being that this could be a hallmark of past life.

Interviewee - Philip Robinson

Well exactly.

Interviewer - Chris Smith 

Or even present life I suppose.

Interviewee - Philip Robinson

Possibly present life, but if it had at one time harboured life, then we might expect to see some of these organic molecules. 

Interviewer - Chris Smith 

But isn't that what Curiosity is set out to do?  It's got a laser that can zap rocks then look at the gas plume that comes off, it's got a whole laboratory, a miniscule laboratory inside it. 

Interviewee - Philip Robinson

Yeah it has, it's incredibly high tech.  It's festooned with analytical instrumentation designed for exactly for this purpose.  However, there are those that say, its mission in that respect is going to be a failure.

Interviewer - Chris Smith 

Why?

Interviewee - Philip Robinson

This isn't the first time that a rover has been to Mars and it's not the first time that it's been there with the purpose of looking for these organics and all previous attempts to do so have also failed.

Interviewer - Chris Smith 

Well can I therefore be devil's advocate for a second and say what if I just went to random bits of space, where we don't think there's any life and never has been, you will find organic molecules because of chemistry going on around stars and just naturally in space, so they should have found something surely.

Interviewee - Philip Robinson

Exactly, so there's a huge question here, which is that regardless of whether or not Mars has ever harboured any life, it should have organic material present on its surface. 

Interviewer - Chris Smith 

What you're saying, you're saying, perhaps the analytical techniques themselves don't work?

Interviewee - Philip Robinson

That is one of the arguments for the reason the failure to find, these organic molecules.  Sam Kounaves of Tufts University thinks what happens when the Martian soil has been analyzed is that certain species that are present there called perchlorates oxidize these organic species and turn them into carbon dioxide and that's why you don't see any of these organic molecules.

Interviewer - Chris Smith 

So, we know that perchlorates are there.

Interviewee - Philip Robinson

We do know perchlorates there, yeah that has been established.

Interviewer - Chris Smith 

So if he is right.  Is there a way around this?

Interviewee - Philip Robinson

So, he's proposed his own solution, which is an alternative analytical device that in fact exploits the fact that perchlorate is present on the Martian soil and it will oxidize the organics.  So, in his analytical instrument, the sample of the Martian soil is fed into an electrolysis device where the perchlorate itself acts as the electrolyte and all of the organic material is oxidized to produce carbon dioxide and then you just detect the carbon dioxide.  So that gives you a measure of the total amount of carbon.  Obviously, he doesn't tell you in what form.

Interviewer - Chris Smith 

Is this something that can be reverse engineered into Curiosity, the present mission?

Interviewee - Philip Robinson

Unfortunately it's too late for Curiosity.  So it's a consideration for future missions. 

Interviewer - Chris Smith 

They will still be able to detect minerals and things like that, weren't they?  which would have been an indicator of a very wet environment, certain temperatures that kind of places where we know life flourishes on earth today and where we think it evolved.

Interviewee - Philip Robinson

Yeah that's what they're really out there looking for is places where life might have been able to survive or have originated.

(4:34 - Fluorine - the most reactive element - has been found in nature)

Interviewer - Chris Smith 

Let's move off a Mars and back to earth because something which was always taught in my chemistry lessons Neil was that fluorine that Tyrannosaurus rex oxidizing element does not exist as F2 in gaseous form on earth because it's just too reactive and now you're going to blow it out of the water.

Interviewee - Neil Withers

I'm afraid I'm going to ruin all the preconceptions about fluorine, elemental fluorine on earth as you have them because Florian Kraus from Munich, he was intrigued by stories, when he was researching his inorganic fluorine class  class he was going to teach that  a mineral known as fetid fluorite contains some fluorine as fetid because of their smell, we thought it might be fluorine, but the thing was that geologists weren't sure if the smell was fluorine or whether it was something else.

Interviewer - Chris Smith 

So when you say smell, people were literally sniffing bits of rock.

Interviewee - Neil Withers

Yes.  So when you break this mineral, fetid fluorite or antozonite, it releases a very characteristic smell, which is quite unpleasant.

Interviewer - Chris Smith 

And people wondered, is this really fluorite because they knew there was fluorite in the rocks.  So they put a sort of leap of faith.

Interviewee - Neil Withers

yes, This is a calcium fluorite, CaF2 mineral, so there is fluorine in some form but he as a fluorine chemist thought he had a good chance of being able to identify, so he found out where he could find some of these rocks,

Interviewer - Chris Smith 

Which is where?

Interviewee - Neil Withers

Which is in W?lsendorf in Germany, so he just drove down there.

Interviewer - Chris Smith 

It's just down the road.

Interviewee - Neil Withers

Just down the road for him, so he drove there, picked up some rocks and took them back to his lab.  He smashed them with a hammer and he smelled the characteristic smell.

Interviewer - Chris Smith 

But how does he know that's fluorine though.

Interviewee - Neil Withers

Well, he then compared that by smelling fluorine gas itself.

Interviewer - Chris Smith 

He really smelled fluorine, but I thought it was really toxic.

Interviewee - Neil Withers

Well, I suppose and he said that in very low concentrations and very briefly, it is safe and the smell of fluorine is so characteristic that he was absolutely sure, that it had to be fluorine.

Interviewer - Chris Smith 

This is a man after Humphry Davy's heart, isn't it? He was famous for sniffing things including entonox but that's a different story.  So, he reckons on the basis of his own olfaction, this is fluorine coming out of these rocks so how did he prove it?

Interviewee - Neil Withers

So he tried to prove it with a mass spectrometer, but he thinks that the fluorine gas was so reactive it was reacting with parts of the spectrometer before it could get to the detector. So he was a bit disheartened that it wasn't working but fortunately, he was talking to one of his colleagues over a social evening of beer and pretzels in a symposium and his colleague works on solid state NMR.  So he persuaded his colleague to put a small sample of the actual rock itself, so not the gas into his NMR machine and they saw the characteristic chemical shift that showed that it is fluorine gas.  So the shift is.

Interviewer - Chris Smith 

Wow! So where did this come from?

Interviewee - Neil Withers

It turns out that antozonite has a small amount of uranium which of course is radioactive, so the beta decay from uranium and from the daughter nuclide causes some of the fluoride anions in the lattice to kind of become dislodged after a bit of a mess you end up with two fluorine atoms coming together to form Fluorine F2 as we know it, and they even observed some bubbles the size of I think 200 nanometres using a electron microscope.

(7:38 - Ruth Mcnerney discusses the challenges in detecting and treating tuberculosis)

Interviewer - Chris Smith 

Thank you Neil.  And now to a scourge that has infected one person in every three and during the time it takes you to listen to this program, it will kill over three hundred people, but why is TB such a problem for whom and where?

Interviewee - Ruth McNerney

My name is Ruth McNerney, I work at the London School of Hygiene Tropical Medicine, a senior lecturer doing research.  I'm also an advisor in trustee of the UK Charity for Tuberculosis (TB) Alert.  There are about 9 million new cases every year of TB.  We have a problem in about 3 million of those we think are not diagnosed so we're talking about estimates.  We're talking about one and a half million people every year dying from tuberculosis.

Interviewer - Chris Smith 

So, we're on the scale of HIV in terms of new cases a day, people dying a day, it's about 10,000 then.

Interviewee - Ruth McNerney

It's interesting.  HIV, it's very closely related disease to TB, the two run together really.  Most people who die from AIDS, which is the HIV disease, they're dying of tuberculosis. 

Interviewer - Chris Smith 

So in other words, geographically, are we seeing a massive overlap?

Interviewee - Ruth McNerney

First and foremost, TB is a disease of poverty, it's in the parts of the world where people are poor, where they're malnourished, but it's also where the HIV is.  So though  the most number of cases are in India and China because that's where the most people live, in terms of the proportion of cases, it's South Africa, southern Africa, Zambia, Zimbabwe, all over Africa wherever you find HIV, you find a huge problem of TB.

Interviewer - Chris Smith 

If you look at some Victorian literature though, you read a bit of Dickens and a few others, there are people dying of "consumption" as it was then known, they didn't have HIV though.  So what happened here, so what's rife and now isn't, and is it still rife in other bits of the world then?

Interviewee - Ruth McNerney

Well, there's lots of contributing factors, it's a lot of that to do with improving social conditions.  People eating better, eventually we've got drugs, but it's interesting that the cases came down very dramatically in Europe as lifestyles got better, people got richer.  So it's very much about people's lifestyle, the pressures they are under,  the way they live their lives, overcrowding, diabetes is a risk factor, smoking is a risk factor, and now of course you got HIV, it's a huge risk factor in Africa.

Interviewer - Chris Smith 

What actually is the problem now because we had got the numbers down here in Britain to really low levels, now they're going back up again; so are we reverting to the Victorian era or is something else driving this recurrence?

Interviewee - Ruth McNerney

Well the problem we are facing is a development of drug resistance, and it's emerging all over the world.  Drug resistance is not a huge problem in UK yet, but in other parts of the world it really is.  We use a cocktail of drugs for TB and you have to treat for months, six months is the shortest treatment for TB and often it goes on for longer than that and if those drugs fail, then you don't get treated, you stay infectious.  If TB spreads, when people cough, they are coughing out the bacteria into the air. So if you can't treat people, they stay infectious and they stay spreading the disease.  So you've got two problems.  One is a lot of the people we don't detect.  Some people don't realize they're sick and if they do realize they are sick, they've got a cough and eventually they didn't call that cough and  if we are looking at , the tests aren't  very good for actually detecting the disease.  And so lot of people miss, don't get the treatment early.  The other big problem is if they've got drug-resistant TB, we put them on the standard drugs so they don't get back to and they continue to transmit, the reason we get.

Interviewer - Chris Smith 

Why are those treatments so long? Why are people having to take 6 months of therapy when if you get a sort of splinter in your finger and a bad infection at the end of your finger onto your finger nail, it's, you know, a week of flucloxacillin and you're better.

Interviewee - Ruth McNerney

Well TB is very interesting bacteria.  It kind of coevolves with humans.  It's very unusual, it grows much more slowly than those other bacteria, the bacteria are E. coli, they double every 15 minutes, it takes just a whole day like 20 hours for TB to double and it can also, it can just sit there and do nothing.  It's resistant to lots of antibiotics, you just can't get inside the bacteria to do any damage. It's resistant to most disinfectants as well and so it's actually very difficult to kill. You can have drugs that will kill it when it's actively growing, but if it's just sitting there and it sits inside organs, inside cells, it's quite hard for drugs to actually find where is the bacteria.  It can just sit there, and it's not growing, most of the drugs can't really kill it.

Interviewer - Chris Smith 

So, it gets inside cells that's where it grows. 

Interviewee - Ruth McNerney

TB, the disease is actually a sort of battle between the immune system and the bacteria.  It gets into the lungs and then it gets the immune system recognizes it and gets to work, but 'it's not effective, it's a horrendous problem, we don't understand why some people develop the disease, some don't.  We think about a third of the world's population like 2 billion people have been affected by TB, but only about a 10 or 15% actually developed the disease and we just can't understand why some people are susceptible.

Interviewer - Chris Smith 

Now when you say that a third of the world population, quite literally more than 2 billion people could have infected with TB.  Does that mean they infected and they stay infected and that it can't come back in them or does it mean that they have cleared the infection?

Interviewee - Ruth McNerney

It probably means both.  We don't really understand.  Certainly you can be exposed to TB, and not develop a noticeable disease, then 30 years later, you can develop TB.  Some people may clear the disease completely.

Interviewer - Chris Smith 

Now looking at the way we're treated, if you take drugs for 6 months to clear it, obviously the compliance is going to be quite poor among patients for that.  Does that lead to resistance?

Interviewee - Ruth McNerney

Yes, it's one of the big factors in resistance.

Interviewer - Chris Smith 

What fraction of the TB that's now circulating, if you were to put people on the standard regime that we would give someone who turned up in the hospital here, what fraction wouldn't respond now?

Interviewee - Ruth McNerney

It varies around the world.  Throughout the UK the rate of drug resistance is very low, there  are other parts of the world like Moldova over half of the patients have got multi-drug resistant TB.  Of new cases, people who've never been treated before, we think between 3 and 4% of them have multi-drug resistant TB.

Interviewer - Chris Smith 

And although it's multi-drug resistant, it's still treatable is it?

Interviewee - Ruth McNerney

It is.  Yes.  We define multi-drug resistance as being resistance to two of the major drugs, Isoniazid and Rifampicin and if you're resistant to those drugs, you're likely to fail treatment if you change to a new treatment.  The new treatments, there are separate treatments there, there are several problems.  One is they're very expensive drugs.  But another big problem is they're actually very toxic, so the side effects are very unpleasant for people, a lot of nausea, so very difficult to take and the problem is then also we've got resistance to those drugs.  And once you're resistant to the second line drugs, then I'm afraid it's very, very difficult to treat.  We've even seen cases now being reported, where what we're calling total drug resistance where the bacteria are resistant to every single drug that's been tested on them so far.

Interviewer - Chris Smith 

And what can we do about it and why are there so few drugs that will tackle TB, really I mean it's been around for donkey's years, I would have thought it was one of those things that was really easy to deal with.

Interviewee - Ruth McNerney

Well there are lots of reasons, well one of the lack of political will.   We thought TB was going away in the world, it wasn't really a big problem, so there wasn't much research going into it. It's not a big money spinner, so drug companies are not going to put lots of money. So there is some research going on. There are some new drugs in the pipeline, but TB bacteria is a very, very challenging bug and you've got this amazing cell wall that's very waxy and to get the drugs in is quite difficult.  So a lot of drugs just bounce off TB eventually they don't work.  Getting a compound that might work is a first step, that's kind of cheap, but then you've got to do very, very expensive studies just to see if they really work or not in a population and they take years because TB takes that long to treat and then you've got to follow-up patient for years to see if they relapse and it comes back again.  So it's a very big investment to get a new drug going.

(15:36 - Can a skin cream deliver insulin and replace daily injections?)

Interviewer - Chris Smith 

Ruth McNerney from the London School of Hygiene and Tropical Medicine.  And now good news for needle phobics potentially, Elinor.

Interviewee - Elinor Richards

Well, diabetics need insulin injections every day.  So insulin is produced by the pancreas and it allows cells to take up glucose from food, to use for energy.  So, a lack of insulin leads to glucose build-up in the blood and this leads to diabetes.  So injecting yourself with insulin can't be a pleasant experience for those who've got needle phobia, I can completely understand.  So scientists have been trying to come up with a more pleasant way to take insulin.

Interviewer - Chris Smith 

But you can't swallow it of course because rather like eating your egg in the morning with lots of protein, it just breaks down in stomach acid, proteases and digestive juices.

Interviewee - Elinor Richards

That's it.  Scientists have worked on getting it in an oral dose, but the concentration just gets reduced in the stomach.  So now a group from Kyushu University in Japan, led by Masahiro Goto have come up with a way of delivering it through the skin.

Interviewer - Chris Smith 

Well, how?

Interviewee - Elinor Richards

Well they've made capsules loaded with insulin, covered them in a peptide that's known for enhancing skin penetration and then they dispersed the capsule in an oil that also has a permeation enhancing effect.

Interviewer - Chris Smith 

What's the protein that gets it into the skin?

Interviewee - Elinor Richards

Well, the protein is oligoarginine.  What they did was they first surrounded the insulin molecules with proteins and then they coated these with hydrophobic surfactant thus forming a protein surfactant complex, then they added the oligoarginine peptides on top of this and then dispersed the complexes in oil.

Interviewer - Chris Smith 

And then what you rub this on or you have a patch or something, how do they use it?

Interviewee - Elinor Richards

I think it's just rubbed onto the skin.

Interviewer - Chris Smith 

And how much goes through.

Interviewee - Elinor Richards

Well, they tested it on pig skin and found that it delivered six times more insulin into the skin, then capsules in an aqueous solution, but we're not quite sure if that's enough of a dose.

Interviewer - Chris Smith 

But it's clinically relevant, because obviously getting it through the needle is very good, I mean that's people are doing but if you can only get a tiny amount through by shoving it on in a cream or a patch or something, it's going to be terribly effective.

Interviewee - Elinor Richards

No I don't think that's something they need to look up. 

Interviewer - Chris Smith 

If this enables things like proteins to go through skin, does that mean then the same technology, regardless of whether it works for diabetes could be used for other drugs or things that are protein based that we want to get in.

Interviewee - Elinor Richards

Yes, the researchers do say that that is their future plan.  They want to produce a vaccine as well that could be delivered through the skin.

(18:08 - Magnetic bonds predicted to exist - but only in the magnetic fields around neutron stars)

Interviewer - Chris Smith 

Which means again good feel needle phobic problem, I suppose.

Interviewee - Elinor Richards

Oh, Yes

Interviewer - Chris Smith 

 All right we'll sort of blast off into outer space for a second because Neil, you got some interesting news for us on the question of neutron stars and the kind of chemistry that goes on there.

Interviewee -Neil Withers

Absolutely. So neutron stars are incredibly dense.  I think a neutron star about the size of the earth would weigh half as much as the sun so they're incredibly dense and they spin very quickly and this generates incredibly strong magnetic fields that are ten thousand or hundred thousand Tesla whereas the magnetic field in an NMR machine or an MRI that we might use in a hospital or in a lab will be around 1 Tesla.  So these are incredibly strong magnetic fields.

Interviewer - Chris Smith 

So with that kind of power, in terms of the field effects what would be the behaviour of various chemicals if they are added in the environment then?

Interviewee -Neil Withers

So it's very hard test this in the lab for example, or we can't go to neutron stars.  So a team from the University of Oslo have computationally looked at the behaviour of simple diatomics like dihydrogen and helium and they found that if just promoting an electron to an anti-bonding orbital in dihydrogen for example, that would normally be enough to tear apart the molecule because it's no longer energetically favourable, but they found in these incredibly tense magnetic field, the molecule would align itself perpendicular to the magnetic field and the interaction between the anti-bonding orbital and the magnetic field would be enough to stabilize it so it wouldn't fall apart. So this kind of magnetic bonding they've discovered that would be complimentary to the normal electron bonding that we know, ionic and covalent and so on.

Interviewer - Chris Smith 

Is this chemically relevant though?  Is this likely to provoke or promote some kind of new chemistry to take place, if atoms and molecules will behave in strange ways in these fields.  Does this mean that other kinds of interactions are possible that wouldn't normally happen and that could lead to some new chemistry?

Interviewee -Neil Withers

I think in terms of the discovery itself, I think the magnetic fields are so strong that it's very, very unlikely that there's ever going to be a practical use on earth or even studied in the kind of glove boxes in strange environments that we can use.

Interviewer - Chris Smith 

But my point is not that.  If you can drive new kinds of chemistry, I don't mean necessarily here on earth, but out in space because of these interesting phenomena that we hadn't accounted for before. 

Interviewee -Neil Withers

I guess, it could mean that in neutron stars there are other effects going on we haven't thought about, but I think that equally the kind of magnetic and high pressure stuff would probably over compensate for these relatively subtle magnetic effects.

Interviewer - Chris Smith 

Not that Blue sky research is the right way to describe that because it's not a Blue sky, it's a neutron star.  It's a sort white colour isn't it?

Interviewee -Neil Withers

Probably yeah.  I have not seen one.

Jingle

Interviewer - Chris Smith 

You're listening to the Chemistry World podcast with me Chris Smith.  Still to come new reasons to worry about ozone depletion and cyborg jelly fish.  First though to a celebrated scientist who is also a worthy recipient of Chemistry World's Entrepreneur of the Year Award.  He has pioneered the discovery of molecularly targeted cancer drugs.  He is also a passionate proponent of personalized medicine and so far he's founded two successful chemical companies.  We began by discussing why and despite huge investment, cancer still remains largely uncured.

(21:03 - Paul Workman, Chemistry World entrepreneur of the year 2012)

Interviewee - Paul Workman

I'm Paul Workman and I'm the Head of cancer therapeutics at the Institute of Cancer Research in London.  I think we've made, you know, incredible inroads.  There are number of leukaemias, there are childhood cancers, where patients are cured. There are breast cancer survivors that are surviving 20 years or more, but it's certainly true that we haven't made across the board, the level of cures that we were aspiring to do and the biggest problems are twofold and those two issues are understanding the molecular basis of cancer so that we can come up with therapies that are more effective than the old one size fits all cytotoxic drugs and we're in the process of sorting that out now and then the second one is the problem of drug resistance which is certainly something that is a major problem.

Interviewer - Chris Smith 

Is the fact that we're getting better at interrogating cancer and understanding what the disease is? Is the fact that it's not advancing a reflection on technology because we now have the ability to probe the genome in unprecedented detail?  What we can do in a day to years, 10 years ago.

Interviewee - Paul