Chemistry World Podcast - November 2008

00:10 --   Introduction

02:40 --   Better than geckos: the glue that clings to walls

05:00 --   How to cure wrinkles with LEDs

07:45 --   Martin Chalfie, one of this year's three chemistry Nobel prize winners tells us how his research changed course when he discovered a glowing green jellyfish protein

13:30 --   Jeff Bada explains how Stanley Miller's 50-year-old origin of life experiments were rediscovered in a lab cupboard

19:35 --   A gentle solution to the chemical problem of breaking up wood to make biofuel

22:22 --   How microscopic diving boards can help drug discovery

25:36 --   What exactly is wrong with the LHC? Brian Cox explains

31:36 --   This month we have a glowing, sweet chemical conundrum

(Promo)

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

(End Promo)

(00:10 --   Introduction)

Interviewer - Chris Smith

Hello! Welcome to November's edition of Chemistry World Podcast with Victoria Gill, Richard Van Noorden, and James Mitchell Crow. I'm Chris Smith. Coming up, our researchers have shed some light on the aging process and how we can stop it. The one downside is that the process seems to take a lifetime.

Interviewee - Victoria Gill

It was disappointingly long time I thought, they did this therapy over a period of about a year and it was, sort of a therapeutic session of about 30 minutes a day and it's a particular device that's been created. It's a medical light therapy device with a quite cool name, it's called WARP 10. Yeah, it's not just a case of sort of shine the LED from your TV remote control at your face and see the results within a week, it does seem to take a quite long time.  

Interviewer - Chris Smith

Victoria Gill ironing out the wrinkles in that aging story. That's coming up very shortly.   Also this year's chemistry Nobel laureate, Martin Chalfie, reveals how he came up with the idea of putting a jelly fish gene into a worm.

Interviewee - Martin Chalfie

But I actually don't remember anything that I heard in the seminar after having this idea. I was so excited. I spent the rest of the day trying to find out who was working on green fluorescent protein and how far they have gotten and I soon found that Douglas Prasher was the person that was trying to clone the gene.

Interviewer - Chris Smith

Martin Chalfie and also on the way how scientists have reincarnated a famous experiment from the 1950s that showed how the early earth could have spawned the building blocks of life. 

Interviewee - Jeffrey Bada

Stanley once reached up and got this   card box down from his bookshelf and said "Hey look, I got some vials in here from my original experiment," and I also realize that that stuff was in my lab, so I came back to my office and lab and we sat down and found these boxes. We opened them up and "Lo and Behold! Here're all these vials from the '53-'54 experiments he conducted."

Interviewer - Chris Smith

Jeff Bada, who found the remains of Stanley Miller's original experiments sitting on a shelf in his lab. He will be telling us what he found when he re-analyzed those materials.   Also on the way of course is the answer to last month's chemical conundrum.

Interviewee - Victoria Gill

It's 50 years since this scientist, the only scientist ever to have won 2 chemistry Nobel prizes, one his first Nobel, what is his name and which protein would you associate him with? So if you sent in a scientific suggestion then you could be one of this month's winners. The answer is on the way.

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(02:40--  Better than geckos: the glue that clings to walls)

Interviewer - Chris Smith

First up this month, James it sounds like scientists have come a step closer to creating a spider-man suit.

Interviewee - James Mitchell Crow

Yes, that's right. Chris you might be able to stick to walls yourself one day. This team of scientists in America have made a material that mimics the surface of gecko's feet and so it can stick very heavy objects to walls and then can detach as well.

Interviewer - Chris Smith

Well, first of all tell us James, how did geckos do it?

Interviewee - James Mitchell Crow

The trick that geckos have is that they have got a surface of very fine hairs on the patch of their feet and that gives a very high surface area. So that gives you strong van der Waals interactions between their toes and the wall. So if you can make a surface that has a similar sort of coating of very fine hairs then you could potentially use the same trick.

Interviewer - Chris Smith

And so is that what these guys have done?

Interviewee - James Mitchell Crow

Yeah, they have made a surface that is coated with carbon nanotubes which when not attached to a wall, it's quite a messy sort of jumbled up surface, but when you attach it to a wall and then put some sort of force on it and it pulls all those nanotubes straight and aligns them and that's what gives you the really high surface area that sticks the stuff to the wall and so they say that.

Interviewer - Chris Smith

Well, I was just going to say on that note, when you plaster it on the wall, does that mean then it is easy to pull off in any direction or does it have the same amount of attraction in any direction that you apply the force to it?

Interviewee - James Mitchell Crow

Well, it's dependent on hanging a force on it and so as soon as you remove the force then the fibre, sort of, tangle up again and so then you can just pull the stuff off very quickly.

Interviewer - Chris Smith

Which makes it very useful because if you can obviously hang a great weight in it but very easily lift it off, it's a bit like a posted noted, I suppose isn't it?

Interviewee - James Mitchell Crow

Yes, that's right. Yes, 3 centimetre squares of this material can hold 150 kilo.

Interviewer - Chris Smith

Is it easy to make and how will we use it?

Interviewee - James Mitchell Crow

They say that is pretty straight forward to make and carbon nanotubes get easier to make all the time and they suggest they might be used for things like the pads of feet of robots for example, so that they might be able to climb walls.

Interviewer - Chris Smith

I did also hear once suggestion that things like this could be useful in space, because astronauts can then put it on the bottoms of their boots and go walking around on the outside of their spacecraft in order to stick them on.

Interviewee - James Mitchell Crow

Yeah, there are many applications that you could think of, where being able to attach and detach from a surface with really high strength would be amazing.

Interviewer - Chris Smith

Thanks James.

(05:00 --  How to cure wrinkles with LEDs)

Interviewer - Chris Smith

Well, from wrinkly feet on geckos to wrinkles on your face. This is very interesting, Vic. You might have a way where you might better shed some light on how we can deal with the problem.

Interviewee - Victoria Gill

Indeed. This work comes out of the University of Ulm and this is a group led by Andrei Sommer who actually looks at the structures of water and it's sort of interactions with surfaces and it's kind of a side study in some of his latest work that he has discovered that light in the form of a penetrating LED light source that's actually used for pain relief and has been used for quite a long time can reduce the wrinkles in your skin.

Interviewer - Chris Smith

What sort of light does the LED pump out?

Interviewee - Victoria Gill

It's visible light. It's the same wavelength of visible light and what they have found is that those wavelengths of light can penetrate the skin and it has been used therapeutically, light therapy for over long time for many decades, but they found a sort of a physical interaction with water molecules in your skin that has a visible effect.

Interviewer - Chris Smith

And tell us a bit more, how does that actually work. What do we think it is actually doing to the skin?

Interviewee - Victoria Gill

So this is all to do with elastin, which as its name suggests is an elastic protein, long fibres of stretchy protein that gives skin its elasticity and young skin can sort of stretch back and reform quite well without forming wrinkles, when you smile. You know, you don't get the crow's feet surrounding your eyes or the smile lines around your mouth.

Interviewer - Chris Smith

Well, at least not straight away.

Interviewee - Victoria Gill

At least not straight away. But as these proteins age, they have a sort of crystal layer of water around them because the actual protein fibres are hydrophobic, they are water hating. So they keep the water on the outside in these sort of interfacial layers, they call them. But as the elastin breaks down as you age, this water gets sort of in amongst the fibres and it forms a viscous layer that stops the fibres from being able to stretch and reform and do their job. So, what they think that the light source is doing is actually physically interacting with these water molecules that are forming this viscous layer, they are stripping the water molecules away, so that elastin can sort be freed up to become stretchy and bounce back again.

Interviewer - Chris Smith

So, how much therapy do you need? Am I going to have to sleep under this thing to preserve by beauty forever or do you need just a few minutes a day?

Interviewee - Victoria Gill

It was disappointingly long time I thought. They did this therapy over a period of about a year and it was a therapeutic session of about 30 minutes a day and it's a particular device that has been created. It's a medical light therapy device with a quite cool name, it's called WARP 10. Yeah, it's not just a case of sort of shine the LED from your TV remote control at your face and see the results within a week. It does seem to take quite a long time.

Interviewer - Chris Smith

Any negative effects?

Interviewee - Victoria Gill

No, it doesn't seem to appear so. No, they have just seen this very happy sort of side effect that if they use this on facial skin and crow's feet, they seem to very gradually, I should put it, disappear.

Interviewer - Chris Smith

So, a little light relief from the effects of the aging process. Thank you, Victoria.

(07:45 --  Martin Chalfie, one of this year's three chemistry Nobel prize winners tells us how his research changed course when he discovered a glowing green jellyfish protein)

Interviewer - Chris Smith

And now on the subjects of light to an illuminating story that led this man to win this year's Nobel prize for chemistry. He is Martin Chalfie and his breakthrough was to take a glowing green gene from a jelly fish and add it to a worm.

Interviewee - Martin Chalfie

Okay, well the story starts with another of the Nobel laureate's Osamu Shimomura. It was his fascination with bioluminescence that led him to try to understand how the jelly fish produced light and he isolated a protein called aequorin. Now aequorin is a light-producing molecule from the jelly fish, but the light that it produces is a blue light and he knew that the jelly fish didn't produce blue light, they produced a green light. So, it meant to him immediately that there must be something else that is converting the energy from aequorin into green light and he found that there was this other protein that he originally called the green protein, now we call it green fluorescent protein that actually took the energy from aequorin and converted in into green light. My involvement occurred many years after he had made this discovery. I was listening to a seminar and as part of the introduction to the seminar, Paul Brehm, mentioned that in addition to aequorin, there was this rather unusual protein called the green fluorescent protein and he described some of its properties. Well, for the 12 years or so before that seminar, I had been working on the nematode Caenorhabditis elegans and the animal was transparent. Since we were at the time doing some gene expression studies, it immediately occurred to me that it would be a wonderful thing if we could possibly have as a marker for gene expression, a fluorescent protein.

Interviewer - Chris Smith

But actually you hadn't worked on the protein before then? How did you actually go about trying to get hold of it and therefore begin to understand how it worked and how you might be able to apply it to the C. elegans, the worm work?

Interviewee - Martin Chalfie

Well, I actually don't remember anything that I heard in the seminar after having this idea. I was so excited. I spent the rest of the day trying to find out who was working on green fluorescent protein and how far they have gotten and I soon found that Douglas Prasher was the person that was trying to clone the gene. He had previously already cloned the gene for aequorin. We had that wonderful conversation and we arranged that we would do a collaboration. The next important step in this story is that I got married, but my wife at the time was at a university, which was about 2000 miles away from where I am here in New York and so I took a sabbatical in her lab. It was just during the time that I was in her lab that Douglas Prasher cloned the gene and he couldn't contact me. I was no longer here at Columbia and then when he tried to call at the University of Utah, people there hadn't learned who I was and so they said, "Oh, no. He's not here." Douglas interpreted this as meaning that I had dropped out of science. About 3 years later, I had a student studying in my lab, Ghia Euschirken and when we were talking I said, well, I'll tell you a wonderful project I'd like to do, but I've never been contacted by the person who is cloning the gene. So we look it up. We look up green fluorescent protein and the first paper that comes up is Douglas Pressure's paper about the cloning of what at the time was called apo-GFP. I called him up and we arranged to continue the collaboration we had talked about several years before and he sent us the cDNA for green fluorescent protein. 

Interviewer - Chris Smith

So then did you get the Ph.D. student in question to begin to clone the gene say into bacteria for example?

Interviewee - Martin Chalfie

Yeah. The first experiment was to put the gene and try to express it into E. coli, which Ghia did and in fact within one month of getting the clone, we had green fluorescent bacteria and we knew that this would work and then when we put it into worms, and it was also fluorescent. We knew that it could be a marker really anywhere.

Interviewer - Chris Smith

And once you got it into the worm, of course, then the floodgates were open because you can begin to use the fact that it is a tiny well-understood model system, transparent with glowing cells now, which you can follow, understand their fates, and work out what difference all you need is to do?

Interviewee - Martin Chalfie

We can do many things with this. So an example from my own lab, we are interested in the sense of touch. There are only six touch sensing cells in the animals. We can express, GFP only in those cells and those are the only cells that have the bright fluorescence. We can then take those animals and look for mutants variant that are unusual in the growth of the nerve cells, either the nerve cells are not there, there is no GFP-positive cells or the nerve cells and our processes that grow in the wrong direction or may be they have abnormal branching pattern and we can look for these defects in nerve development simply by looking at the animal and seeing how these cells are different from the wild type or normal animals.

Interviewer - Chris Smith

Columbia University's Martin Chalfie, one of the winners of the 2008 Nobel Prize for Chemistry. And if you're wondering what happened to Doug Prasher, the man who cloned the GFP gene in the first place and then collaborated with Martin in the early days. Well, because he was unable to secure a further funding for his work, Martin tells me that he now drives a bus. How is that for scientific justice?

(Music)

(13:30 --  Jeff Bada explains how Stanley Miller's 50-year-old origin of life experiments were rediscovered in a lab cupboard)

Interviewer - Chris Smith

This is the Chemistry World podcast, with me Chris Smith. Still to come, better biofuels. Scientists have found a more effective way to liberate the beneficial chemicals in wood and also Brian Cox joins us to explain what exactly has gone wrong with the LHC. But first, to a story that began in the 1950s with a paper published in the journal, Science by California-based researcher, Stanley Miller. He showed that the conditions on the early earth could naturally have produced some of the building blocks of life and now 50 years later, one of his former co-workers has found the original material that was produced in those experiments and subjected it to modern-day chemical analysis. Here's Jeff Bada.

Interviewee - Jeffrey Bada

Well in 1953, Stanley Miller, published a short paper in Science, describing how you could synthesize amino acids which are components of all living organisms today in a model primitive earth experiment and what he did is he took methane, ammonia, hydrogen and applied an electric spark to it, sort of to simulate a lightening in the early atmosphere and in that he produced like I said amino acids which was a great breakthrough, because all of a sudden we had evidence that you could create raw materials ought to be necessary for the origin of life in a simulated prebiotic earth environment. And fortunately going from amino acids to more complex molecules has proven to be a bigger challenge in making the simple molecule themselves, but we are making progress in that area.

Interviewer - Chris Smith

What was your kind of role in the present paper that you've just published in Science?

Interviewee - Jeffrey Bada

I was Stanley's second graduate student, so I've been immersed in this whole field of prebiotic chemistry and the origin of life my whole career and just by chance another dear friend of Stanley's, Antonio Lazcano and I were in Texas to give a series of back-to-back lectures and Antonio said, by the way, you know, Stanley once reached up and got this card box down from his bookshelf and said, "Hey look, I got some vials in here from my original experiment." And I also realized that that stuff was in my lab. So I came back to my office and lab and we sat down and found these boxes. We opened them up and "Lo and Behold! Here are all these other little boxes inside with vials clearly labelled, indicating that they came from the '53-'54 experiments he conducted 

Interviewer - Chris Smith

And he had actually kept those pristine, so you can be reasonably confident that the material in there was the material that he synthesized in those experiments. 

Interviewee - Jeffrey Bada

Absolutely, because they were very meticulously collected and stored and labelled and it turned out that his laboratory notebooks were present in the archive at the UCSD Library and so we went up and looked at his notebooks and we were able to assign each of these various boxes of vials to a specific experiment that he had conducted in '53-'54. I was particularly interested in one experiment that he had conducted using a different apparatus that had an aspirator on the flask where the water was boiled and what this did is it produced a jet of hot steam directly into the spark chamber and I was intrigued by the possibility of how this might mimic a steam-rich volcanic eruption, particularly since we now know that volcanic eruptions are accompanied by very intense lightning. The surmise here was that you could have a volcanic system that was belching reduce gases and these were immediately subjected to lighting. This resulted in local synthesis of amino acids rather than a global synthesis that Stanley had imagined.

Interviewer - Chris Smith

So, how did you then go about analyzing the vestiges of what was in those flasks to see whether or not it agreed with what he had published and if there was anything else lurking in there?

Interviewee - Jeffrey Bada

The first thing we did is we carefully suspended, you know, the residues in water and took a very tiny (UNCLEAR 17:34). With today's modern analytical techniques, we have sensitivities that are many million times better than what he had available. The first thing we did is look at it and see okay, is there anything here into the compounds that we see that he had identified looked to be in the same proportions and sure enough he had identified five amino acids in each of the experiments with a different apparatus, but more intriguing was that the compounds that we could detect that he didn't have the capability of detecting were much more diverse than we could have imagined.

Interviewer - Chris Smith

So, how much more was lurking in there than Stanley Miller thought?

Interviewee - Jeffrey Bada

Well, he identified five amino acids and we've now identified over 22. In the Science paper we stopped at C6 amino acids, I would safely guess that the actual number of compounds that are present in there could be approaching up to 50 or so.

Interviewer - Chris Smith

So this sounds like an amazing breakthrough really because it adds a lot of credence to this early model that the early earth was actually spawning all kinds of interesting soups, which could quite well have produced some quite exciting chemistry.

Interviewee - Jeffrey Bada

Oh! Absolutely, and I hear today the comment that most of the scientists think that the atmosphere wasn't reducing. It did not have methane and ammonia and hydrogen and thus the Miller experiment is irrelevant and I take exception to that because what I think is happening is you could've had all these little hotspot volcanic island type systems on the early earth and they could have been locally synthesizing amino acids that could have been then part of the global prebiotic soup and so instead of having a sort of a global synthesis, you had all these little tiny chemical factory, sitting on the surface of the earth, producing the ingredients necessary for the origin of life. 

Interviewer - Chris Smith

Amazing to think that that box containing all that material has been sitting on a lab for over 50 years. That was Jeff Bada from the University of California, San Diego, reanalyzing Stanley Miller's original work on the origins of the building blocks of life. 

(19.35 --  A gentle solution to the chemical problem of breaking up wood to make biofuel)

Interviewer - Chris Smith

We are now to some more modern experimentation and this time into biofuels because scientists assume that you need to treat your wood gently, James.

Interviewee - James Mitchell Crow

Yes, that's right. You should be good to it because it could be potentially a source of fuel and thanks to some new research done by Ferdi Sch?th and colleagues at Max Planck in Germany. He's worked out a new, easier way to breakdown cellulose fibres from wood and sort of, related waste plant material into short chains which could then be fit enzymes to be broken down into sugars like ethanol, which could be a potential fuel, so a biofuel.

Interviewer - Chris Smith

Why do we need this and why haven't we been able to do this before?

Interviewee - James Mitchell Crow

We have been able to break down cellulose before, but it takes really a harsh treatment, for example, you have to use very strong acid or very high temperatures and pressures to break it down because the sugar chains that make up the cellulose and they're sort of tangled up into microfibres within the wood and that sort of protects the bonds from easy chemical attack, which is why it's been a problem to break the cellulose down. The reason we really want to do it is because cellulose is a hugely abundant stuff and is not a food, we can't break it down ourselves in our guts and so it could be a potential source of fuel that wouldn't impact on food supplies, you could just use food waste or the sort of leftover agriculture waste.

Interviewer - Chris Smith

And so this new technique, how does it work?

Interviewee - James Mitchell Crow

What he has done is he has taken an ionic liquid and an acid resin. It turns out that cellulose will actually dissolve in ionic liquids. You can actually put in small wood chips and they will slowly break down. So once they are dissolved, if you also add in a solid acid resin then that acid is enough to start breaking down those long chains into smaller pieces. Once you started to breakdown the chains and then that means that other techniques for example, enzymes that can be used to breakdown those short chains into the sugars.

Interviewer - Chris Smith

And is this actually scalable? In other words, is this practical at an industrial or even a domestic level? 

Interviewee - James Mitchell Crow

Well potentially, yes, should say that he is actually in talks with BASF to look at the industrial potential of this technique. The slight downside with the technique is that to get these shorter chains out of the ionic liquid, you have to add water, they dissolve in the water and then you separate the two, but that separation takes quite a lot of energy, so that's the downside.

Interviewer - Chris Smith

I was just going to say does this actually make energetic sense, is it worth doing this?

Interviewee - James Mitchell Crow

It's going to need a little fine tuning but potentially this could be a neat way.

Interviewer - Chris Smith

Thanks James. So let's hope that we can all power our cars by putting not a tiger in your tank, but perhaps an oak tree in future, who knows? 

(22:22 --   How microscopic diving boards can help drug discovery)

Interviewer - Chris Smith

Richard, this is very interesting and you waited to take drugs using a cantilever.

Interviewee - Richard Van Noorden

That's right, Chris. This is fascinating stuff from researchers in the UK, Australia and Kenya and they're using arrays of tiny cantilevers as you say, tiny micrometer thin diving boards of silicon as sensors to detect the binding between drugs and their targets. So what's going on here is that on your diving board, you've covered it with receptors that your drug is going to attack and when your drug comes in and binds through the receptors, it causes the board to bend. Now this is already being known, it's already been used to detect various number of biochemical interactions, but what the researchers do here and they are led by Rachel McKendry, University College London is that they can use arrays of boards and they can screen very very rapidly, very high throughput screen for patent drugs. They can screen thousands of drugs an hour and if you have different receptors on a different board, you would be able to screen lots and lots of variants of the same drug 

Interviewer - Chris Smith

And presumably this is a way of determining how tightly the drug bonds or locks onto those receptors, so you can work out affinities and all that kind of stuff.

Interviewee - Richard Van Noorden

Yeah, what this team have done, you might not think it's possible, but they've actually related the bending of the board mathematically to the affinity of the drug to the receptor, which is pretty clever and then a completely different way of working out, binding interactions. What they actually did in practice is they looked at the interaction between vancomycin, an antibiotic and an artificial amino acid sequence that mimics what it attacks in the bacterial cell wall and having shown that the cantilever bends w