Chemistry World Podcast - July 2008

00:10 --   Introduction

02:07 --    Taking fingerprints from wiped metal with the help of chemistry

05:00 --    A new way to capture carbon from the air

07:34 --    Synthetic biology part I: John McCarthy from Manchester University explains how synthetic biology could help design new biofuels

13:30 --    Waking up and smelling the coffee could be enough to soothe the sleep-deprived brain

15:12 --    Computer-designed insect repellents

18:00 --    Synthetic biology part II: Jason Chin from Cambridge University on engineering cells capable of producing completely novel proteins

23:12 --    The makers of Botox release a drug that could make your eyelashes grow longer

25:33 --    A new family of high temperature superconductors

28:34 --    What compound is responsible for red wine's health-boosting properties? And you could win a brand new set of RSC Visual Elements top trumps

(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 the Chemistry World podcast with Mark Peplow, Ananyo Bhattacharya, and Richard Van Noorden, I'm Chris Smith.   Coming up we will be looking at the cosmetic equivalent of fertilizer for eyelashes, although there are some consequences.

Interviewee - Ananyo Bhattacharya

The same drug maker that brought you Botox has now come up with a new cosmetic drug that could make your eyelashes grow longer.   The US Pharma firm Allergan has confirmed that they're going to be applying for approval for their drug Lumigan.   It is known to cause eye reddening and it also darkens your eyelid and also causes darkening of your eye colour and that could be permanent.

Interviewer - Chris Smith

Well, that's certainly one to keep an eye on.   Also we have scientists who have taught a computer to beat off mosquitoes better than we can.

Interviewee - Mark Peplow

A group of scientists at the University of Florida have effectively trained a computer to predict the structure of insect repellent molecules and they've actually found several that are much more effective than the current 'gold standard' repellent, DEET.

Interviewer - Chris Smith

And we also take a look at the science of synthetic biology and artificial life.

Interviewee - John McCarthy

Beyond that of course there is the rather more controversial, potentially of going the whole hog towards creating the relatively basic living cell, in other words, creating a system that can replicate itself and perform metabolism, essentially like any living cell that had naturally evolved.

Interviewer - Chris Smith

That's Manchester University's John McCarthy.   You can hear more from him coming up shortly.   In the meantime did you manage to solve last month's chemical conundrum?

Interviewee - Mark Peplow

What is the name of the compound in red wine that is lauded for its health-giving properties?

Interviewer - Chris Smith

Well, the answer is on the way and if you sent in a chemical solution, then stay tuned to find out whether you are one of our winners this month.  

(Promo)

The Chemistry World podcast is brought to you by the Royal Society of Chemistry.   Look us up online at chemistryworld dot org.

(End Promo)

(02:07 --   Taking fingerprints from wiped metal with the help of chemistry)

Interviewer - Chris Smith

First Mark, you've got news of a way to fingerprint, the previously unfingerprintable.

Interviewee - Mark Peplow

That's right.   Forensic scientists have developed a way to take fingerprints from metal surfaces that had been wiped or heated.   This is a group of scientists working at the University of Leicester along with Northamptonshire police.   Basically they realized that conventional fingerprinting techniques which rely on highlighting the sort of ridges of natural oils that are left on surfaces when people touch them.   In essence it is quite limited because if a surface has been wiped, we've all seen it on cop shows, the guilty man just wipes off a gun with a handkerchief and magically there are no fingerprints left.   So this is, kind of, a limitation of conventional fingerprinting.   What they've done is to look much closer at the surfaces and found that the chloride ions from the salt in people sweat, actually etches in permanently fingerprints into metal surfaces, particularly soft metal surfaces like brass.

Interviewer - Chris Smith

So what you're saying is that you leave a permanent chemical impression of yourself behind on the surface in the form of, well for want of a better term, a rust pan.

Interviewee - Mark Peplow

Yeah, that's right.   The question is, can you actually magnify that enough so you that can actually detect it and they found that yes indeed you can.   The way that they do it is first of all you take your metal sample and you wash it in hot soapy water, so as to actually remove all the grime and all those other traces of oily fingerprint residue and then they put an electrical charge of about two and a half thousand volts across it and add this fine conducting powder, so it's quite similar to photocopier toner and that preferentially adheres to all the corroded ridges.

Interviewer - Chris Smith

So, do we know why the powder sticks preferentially where the ridge pattern is?

Interviewee - Mark Peplow

Well, one of the scientists that we spoke to, John Bond says that the corrosion leads to impurities and sort of imperfections in the crystal lattice on the metal surface and that increases its resistance, so it makes grains and the metal particles preferentially stick to those areas.

Interviewer - Chris Smith

So once you've got your image where do you go next with it?

Interviewee - Mark Peplow

Well, what they are doing at the moment is being able to take that image and use sort of conventional fingerprint databases to compare it.   One of the areas which they think they are going to try and fence this in particular, in gun crime.   One of the scientists points out that the corrosion that you see from the chloride ions on the metal surfaces is actually accelerated by heat, for example when you discharge a fire arm you can imagine that when you're putting bullets into a gun, you have to press quite hard on them.   So combination of pressing down on the bullets and the heating that is involved in actually firing them means that these should be a prime place to actually look for these sorts of corrosion fingerprints.   Now they've done some trials on spent cartridges and actually they have only been able to retrieve prints from a few of them at this stage, but they think that as they develop the technique they should be able to get more of these things off gun cartridges.

(05:00 -- A new way to capture carbon from the air)

Interviewer - Chris Smith

ThanksMark, well from recovering fingerprints from the previously unfingerprintable we move to our carbon footprint Richard, and may be a way, to do with it.

Interviewee - Richard Van Noorden

Well, yes Chris, this is a fantastic way to try and suck carbon out of the atmosphere.   Now this is the work of Klaus Lackner at Columbia University and colleagues at his company, Global Research Technologies and for some years, ever since GRT was founded in 2004, they've been saying why don't we suck carbon out of the atmosphere and try and mitigate global warming.  

Interviewer - Chris Smith

But it is in very low concentration, isn't it.   Doesn't that kind of make it difficult to do?

Interviewee - Richard Van Noorden

Exactly, it's only a 380 ppm or around about that and that means you need chemicals that bind very, very strongly to the gas molecules to quickly get them out of the air, and that means, you really have to get, over kill something like sodium hydroxide that will (UNCLEAR 5:41) the carbon dioxide molecules out, which makes it very hard to rejuvenate the sodium hydroxide again afterwards.

Interviewer - Chris Smith

And so what's their strategy?

Interviewee - Richard Van Noorden

It turns out that they've discovered some ion exchange resins of the salt used in water softeners, It's known that they absorb CO2, but what Lackner discovered was that when you raise the humidity, expose them to warm steam, the CO2 will come off again.   So instead of using sodium hydroxide, and pulling the CO2 out strongly, you're pulling it out weakly, and you can use a humidity swing, or some kind of change in temperature, to get the CO2 back again.

Interviewer - Chris Smith

Which makes the whole thing much more efficient presumably and cheaper?

Interviewee - Richard Van Noorden

The key thing is that it saves energy efficiency as you say.   Now what Lackner thinks is that he'll have millions of these filters all over the world.   They'll each cost a lot to make, 100,000 for just the prototype, which they've taken to develop for about 2 years.

Interviewer - Chris Smith

So once you've got the carbon dioxide in the gel and then you release it with the humidity swing, what do you then do with it?

Interviewee - Richard Van Noorden

Right, what you do is you have ended up with carbon dioxide and water.   They've to exclude air from this when they release it in the swing.   You then of course need to get that out of the way and dry the membranes, you need may be desert's air; where else can be, very dry surrounding air.   Now with your carbon dioxide and water, you can convert that to synthetic fuels using the Fischer-Tropsch reaction.  

Interviewer - Chris Smith

And what does the Fischer-Tropsch reaction do? What is it?

Interviewee - Richard Van Noorden

A Fischer-Tropsch reaction turns carbon dioxide and water into hydrocarbons, so it's very well understood chemistry.   Now the other option is that you could pipe your water and carbon dioxide for say, use in greenhouse to help plants grow, which is already being done from some power plants.   And so this is another thing Lackner wants to do or finally you could just bury underground with the water and the carbon dioxide will, sort of, fizz out of the water as you push it underground.   So these are all the options Lackner is considering.

Interviewer - Chris Smith

Well, who would have thought that the solution to successful CO2 sequestration, which is just sitting inside the average kitchen dishwasher, thank you Richard.  

(07:34 --   Synthetic biology part I: John McCarthy from Manchester University explains how synthetic biology could help design new biofuels)

Interviewer - Chris Smith

Nowtalking of tailor-made solutions to the World's problems, scientists have recently begun to ask whether we can take the processes that drive life and alter them to produce the biological equivalent of a Savile Row suit, in other words, something that's made to measure to do a certain job much better.   Well, that's the field of synthetic biology and someone who is at the heart of that is Manchester University's John McCarthy.

Interviewee - John McCarthy

Synthetic biology is linked in a fundamental way to an approach to biology called systems biology.   Living systems are built from a wide range of biomolecules including proteins, nucleic acids, and lipids, which are assembled like building blocks into complexes and these are then put together to generate cellular functions.   Now sequencing technology has advanced enormously so that we can now analyze the sequences of all of the genes in genomes, even of complex organisms and so we understand what all the components are and with the known identities of all the components, we consider assembling them in different ways in new ways into human design systems and this is what synthetic biology is really about.

Interviewer - Chris Smith

What sorts of things are people trying to do?

Interviewee - John McCarthy

Well, synthetic biology, I think has two sides to it.   The first is things like the production of biofuels.   There is hope and a lot of investments in the United States that new biofuels will be generated by recombinant organisms that have been created through synthetic biology, for example mid-length hydrocarbon chains that can be used as substitute for oil-based fuels.   Then there are biosensors where one might make relatively cheap sensing systems based on living cells, where you introduce circuits into the cells genetically, which enable them to for example, sense particular molecules in the environment, environmental sensors, which for example could pick up the presence of arsenic in drinking water and things like that.   Then you have the area of therapeutics and there are probably going to be hybrid devices ultimately, which combine products of synthetic biology, generated by cells with inorganic materials, but the other area of synthetic biology which I think is equally as important is it can be used to test fundamental principles of function of naturally evolved systems, in the sense that if you really want to demonstrate that you understand how living systems work you should be able to test your models of function, by designing new systems predicting how they behave and actually testing whether they do behave the way that you think they do.

Interviewer - Chris Smith

But that's already happening isn't it? Because we've had some tools to enable scientists to do that for quite a while, so in what ways is that moving on now?

Interviewee - John McCarthy

Well, genetic engineering, I think, is what you are really referring to.   Genetic engineering has been around for sometime.   Distinction between genetic engineering and synthetic biology is very much in the extent to which rigorous engineering principles are applied in synthetic biology.   The approach that is taken involves essentially designing a system, modelling it computationally and then constructing it and testing it, and then going through what is essentially, typically engineering cycle of optimization.   So it is a very quantitative and precise process.   Much of genetic engineering in the past has been pretty qualitative and focused on say the production of one particular product through the construction of pretty simple pathways.   Synthetic biology can really reach up to quite high levels of complexity.

Interviewer - Chris Smith

And what do you think now is the really big challenge for synthetic biology? What would be the Holy Grail that you would like to see solved in the next few years?

Interviewee - John McCarthy

If you ask many synthetic biologists, particularly working in companies, that have sprung up in the US in recent years, the Holy Grail for them would be to essentially design and create synthetic biological systems that will generate biofuels that are economic and can indeed substitute for natural oil-based fuels, but I think also again equally is important will be to demonstrate how valuable synthetic biology is to understanding living systems and that will come through demonstrating our ability to construct, using components that we have derived survive from natural systems, in many cases significantly modified, to generate systems whose behaviour we can predict and test and therefore that will demonstrate a real advance in our understanding of the fundamental principles by which biomolecular systems are actually constructed, because it will put you down on a quantitative footing.   Beyond that of course, there is the rather more controversial potential aim of going the whole hog towards creating from molecular components, at least a relatively basic living cell.   In other words, starting from just the molecules themselves, creating a system that can replicate itself and perform metabolism, thus essentially behave like any living cell that would have naturally evolved.   I think that is the far more ambitious aim of some people and one which probably arouses the most interest in the media, about perhaps the most concerns.

Interviewer - Chris Smith

John McCarthy, who is the director of the Manchester Interdisciplinary Biocentre at the University of Manchester.

(Music)

Interviewer - Chris Smith

This is the Chemistry World podcast with me Chris Smith.   Coming up, how an artificial neural network has shown scientists some powerful new mosquito repellent and also luscious lashes, the new drug that'll make your eye lashes grow, but it could also make your eyes change colour.

(13:30 --   Waking up and smelling the coffee could be enough to soothe the sleep-deprived brain)

Interviewer - Chris Smith

But first though Ananyo there's every reason to suspect that it really is time to wake up and smell the coffee.

Interviewee - Ananyo Bhattacharya

Yeah, that's right Chris, because according to researchers in Germany, Japan, and Korea, the smell of coffee alone could be enough to sue the sleep-deprived brain.

Interviewer - Chris Smith

Sounds good for doctors, what have they done?

Interviewee - Ananyo Bhattacharya

They've taken a group of rats and kept them awake for 24 hours then allowed some of them to sniff coffee and for others they've not allowed them that particular pleasure.

Interviewer - Chris Smith

And then how did they tell the difference between the two groups?

Interviewee - Ananyo Bhattacharya

They looked at the brains of the rats afterwards and checked to see what genes were being activated in their brains and they found that in the rats that hadn't smelled coffee, there were also some proteins that were associated with stress being expressed; the genes that were encoding these were very active.   On the other hand, when they looked at the rats that had smelled the coffee, what they found was there were some levels of antioxidant type proteins, proteins that were helping them to deal with cell damage for example.  

Interviewer - Chris Smith

Which argues that coffee could have a protective effect?

Interviewee - Ananyo Bhattacharya

Yeah, potentially and it's something that the researchers want to explore further.   But for the moment, it looks like even the smell of coffee for those who are staying awake all night could be enough to keep you going for a while.

Interviewer - Chris Smith

But one has to wonder if the reason these rats were stressed when they didn't smell coffee is because they were addicted to it, because they've been used in these experiments before and therefore the reason they were stressed is because they were being deprived of something they are addicted to whereas their counterparts who did get to smell it felt better, because they were getting the drug they were craving, what do you think?

Interviewee - Ananyo Bhattacharya

Yeah that would, sort of, be a Pavlov's Dog type response, but the rats in the experiment haven't been exposed to coffee before or even the smell of coffee.  

(15:12 --   Computer-designed insect repellents)

Interviewer - Chris Smith

Well, from smelling coffee which is something I do like doing to mosquito smelling something that I definitely don't like, Mark.

Interviewee - Mark Peplow

Yeah.   This is all about insect repellents, a group of scientists at the University of Florida, have effectively trained a computer to predict the structure of insect repellent molecules, and they've actually found several that are much more effective than the current 'gold standard' repellent, DEET.

Interviewer - Chris Smith

How have they done it?

Interviewee - Mark Peplow

Well effectively, they have used an artificial neural network.   It's kind of a computer program that can be trained to recognize patterns in large complex sets of data.   First of all, they trained the computer by giving it 150 molecules, which were already known, a class of molecules called Acylpiperidines and they told the computers to take note of various aspects of the molecules, the structure, the position of the atoms, the number of bonds, all that sort of things and crucially how good they were as insect repellents.

Interviewer - Chris Smith

So these were molecules that were already known about, they had already been tested as repellents.

Interviewee - Mark Peplow

That's right and it allowed the computer to build up a portrait of what a good insect repellent looked like, then the researchers presented the neural network with 2000 molecules, many of which had never been made before and so they're going to tell us which ones are going to make good insect repellents.   It picked out 34, which it thought was good repellents and 23 of those were new and had to be synthesized from scratch.   So they got all these compounds and they simply tried them out on volunteers.   They put it on volunteer's skin and exposed the volunteers to mosquitoes.  

Interviewer - Chris Smith

They must have paid these volunteers a lot.

Interviewee - Mark Peplow

They were certainly very willing volunteers and amazingly they found that several of the compounds in the test retained that potency, much, much longer than DEET.   In the best case, the compound was active for 73 days of repelling mosquitoes compared with about seventeen and a half days with DEET.

Interviewer - Chris Smith

Now the really interesting thing they must be the same strategy, the core building blocks that they've put together to make this neural network work must presumably also work for other molecules, things like antibiotics.  

Interviewee - Mark Peplow

This is one of the most interesting things about the story I think, because it illustrates, where chemists (UNCLEAR 17:18) able to use these sorts of neural networks, computer programs that you are able to give them a vast amount of data and say learn the patterns and then predict where we should go next in exploring what some chemists call chemical space if you like the all possible molecules that are out there to be made and you will be seeing the same sorts of things coming through in drug discovery now where you can get this sort of computer prediction if you like, that can at least help chemists to put sign posts, to say this is the most promising angle that I've come up with after comparing tens or hundreds of thousands of compounds and looking at their efficacy.

Interviewer - Chris Smith

So quite literally research on the fly, thank you Mark.

(18:00 --   Synthetic biology part II: Jason Chin from Cambridge University on engineering cells capable of producing completely novel proteins)

Interviewer - Chris Smith

We are back to synthetic biology now and Jason Chin who is a scientist at the Laboratory of Molecular Biology in Cambridge.   One of the things he has been looking at is, how to engineer cells to use artificial amino acids, so that they can construct into wholly novel types of proteins.

Interviewee - Jason Chin

Synthetic biology you know is an area we are trying to design biology to make molecules and cells that have new functions and my particular interest in this is, historically has been in evolving, creating new components for the translational machinery of the cell, that which is the part of the cell that deals with making the proteins that run all the functions in the cell.

Interviewer - Chris Smith

And how do we think we can exploit a better understanding of that?

Interviewee - Jason Chin

Well, we can start to engineer the translational components of the cell which are the molecules in the cell that carry out the function of making proteins and polypeptides using the information encoded in the DNA sequence.   One example of that would be work on engineering the enzymes called aminoacyl-tRNA synthetases and tRNAs which are the enzymes that are responsible for putting individual amino acids into proteins in response to the codons in the DNA, basically translating the genetic information into proteins that carry out the function in the cells and one of the things that we have done is to alter these enzymes and these aminoacyl-tRNA synthetase enzymes and tRNAs such that they can put particular non-natural amino acids into proteins.

Interviewer - Chris Smith

So, what does that mean because we are comfortable with the fact that DNA turns into a protein by assembling clusters of amino acids in the right order, but what is a non-natural amino acid?

Interviewee - Jason Chin

There are 20 natural amino acids and they all differ in what's called the side chain of the amino acids so that's the part of the amino acid that has a distinct chemical functional group or a distinct chemical property.   So some of them are acids, some of them are bases, some of them are more hydrophobic and so non-natural amino acid is any amino acid that just is different or has a different amino acid side chain from one of the natural 20.

Interviewer - Chris Smith

I guess that, that repertoire of 20 amino acids means that there are some constraints on the kind of jobs that proteins can do, which is why people like you, would now want to try and see   if you can change them.

Interviewee - Jason Chin

Yeah that's right.   So, one example of that is in the area of protein therapeutics, where for example things like human growth hormone also another protein therapeutics, are generally derivatized in a chemical way with molecules like polyethylene glycol and this is traditionally done to make a better protein therapeutic by, for example, increasing the amount of time that the protein therapeutic is available to do its job in the body.   But the problem with this is that traditionally this has been done by essentially derivatizing or labelling the natural protein with chemically reactive version of polyethylene glycol and that gives you essentially a mixture of different proteins that are derivatized to different extents, so you get a distribution of molecules and that is essentially what historically people have taken as in these protein therapeutics.

Interviewer - Chris Smith

So in other words, if you've got the protein chain the polyethylene glycol will stick onto certain amino acids at certain places to different extents and some proteins may have a lot in one region and none in another and so you get that population which are going to be different and therefore they won't have a homogeneous effect or biochemical profile in the body necessarily, which will affect their usefulness.

Interviewee - Jason Chin

Exactly, one of the applications of the technology that I described to you is to be able to put a non-natural amino acid into a version of a protein therapeutic at a very specific site and then to be able to derivatize that amino acid or attach polyethylene glycol specifically to that new non-natural amino acid because of some particular chemical property of that non-natural amino acid.

Interviewer - Chris Smith

And so that amino acid would be a, sort of, handle where the new chemical, the polyethylene glycol could cling on, will we have to effectively rewrite the genetic code or redesign some key elements inside a cell in order to make things help this happen?

Interviewee - Jason Chin

That's one of the things that we've done is to reprogram or engineer the aminoacyl-tRNA synthetase enzymes, so that particular new aminoacyl-tRNA synthetase enzymes that we have created recognize specifically the non-natural amino acid but no longer recognize the natural amino acid and are able in combination with the tRNA to put that non-natural amino acid into a protein in response to a particular codon in the mRNA which is not used by natural protein synthesis.

Interviewer - Chris Smith

And is this change heritable, are you going to have to go through all this rig 'n' roll every time you want to do this or have you now got cells that would carry this trait from one generation to the next, so what you have to do is to change the protein that you're making and it would get functionalize the same way every time.