Chemistry World podcast - August 2013


Audio Files

The Chemistry World podcast is sponsored by Waters – world leaders in innovative analytical science solutions. Visit waters.com for more information.

1.11 US researchers have discovered a biological mechanism that contributes to the remarkable cancer resistance of naked mole rats - Gooey secret of naked mole rat's cancer resistance revealed
 
4.42 Cancer researchers in the US and China have combined the turmeric spice pigment curcumin and the drug thalidomide to create hybrid compounds that can kill multiple myeloma cells - Thalidomide teams-up with turmeric to kill myeloma cells
 
7.23 Peeling back the layers of the ribosome, the cell's protein building machinery, can help to shed life on the chemical origins of life. We hear more from Loren Williams - The ascent of molecules
 
14.32 A new NMR method aims to highlight errors in proposed molecular structures before you start trying to make them, preventing the frustrating situation of chasing molecules that never existed - An end to chasing molecules that were never there?
 
18.25 An international team of scientists has used synchrotron-based imaging techniques to chemically map the feather colours of a 150 million-year-old bird - Plumage pattern revealed in 150 million-year-old bird
 

21.39 - How do we make, and safety assure, new drugs for animals? Kevin Greenlees explains the FDA process - Animal pharm
 
28.40 - Why is mercury a liquid at room temperature? If you ask that question in a school classroom you will probably be told that relativity affects the orbitals of heavy metals, contracting them and changing how they bond. However, the first evidence that this explanation is correct has only just been published. Relativity behind mercury's liquidity
 
32.52 - A US high school teacher and nine of his students have made nanoparticles that can neutralise venom from one of the most dangerous snakes in Africa. These nanoparticles could offer a way to make cheaper and more practical antivenoms - Students develop antivenom in high school lab
 
35.53 - Trivia - How did the birth of a royal prince further the study of anaesthetics in the UK?
 

Full Transcript

Interviewer - Chris Smith

This month what colour was an archaeopteryx? Not a trivial question to answer in something that's more than a hundred million years old. Also how biology has its own fossil record.

Interviewee - Loren Williams

There are parts of the ribosome which are basically exactly conserved in everything alive and what that means is that that part of the ribosome has not changed over many billions of years. It is the most permanent object in the known universe.

Interviewer - Chris Smith

And how a high school project resulted in an antidote for cobra venom. That's all to come in this, the Chemistry World Podcast which is sponsored by Waters who are world leaders in innovative analytical science solutions. You can visit waters.com for more information.

(1:11 - Gooey secret of naked mole rat's cancer resistance revealed)

Interviewer - Chris Smith

Hello, I'm Chris Smith and with us for this, the August 2013 edition of Chemistry World Podcast are Jen Newton, Dan Johnson and Patrick Walter who has been looking at a story about an unusual creature with a rate of cancer much lower than it should be.

Interviewee - Patrick Walter

A naked mole rat is a really unusual creature that lives in Africa. It’s hairless, pretty much blind and usually it lives eusocially. It’s about the only mammal that does, really, so they live in a hierarchy like ants with queens, workers and drones and they don't feel any pain..

Interviewer - Chris Smith

And so who has been studying what the underlying mechanism behind this low rate of cancer is?

Interviewee - Patrick Walter

Vera Gorbunova and Andrei Seluanov, at Rochester University in the US. They've had a paper just come out in Nature which is all about this unusual polymer. So, what they discovered is that the hyaluronic acid in the naked mole rat in extracellular matrix was five times bigger than you'd normally see in mice or humans. So, the polymer chain is extended, much larger, this gives you a much more viscous, a kind of a gooey centre to the extracellular matrix. Why on Earth is it stopping naked mole rats getting cancer? It’s because of something called a contact inhibition mechanism. So, when cells divide, the closer they get when they're kind of elbowing up against each other. Once they're jostling together, they then get a signal to stop dividing. This is a cancer protection mechanism, it prevents rapid proliferation. And in the case of the naked mole rats, this gooey extracellular matrix actually introduces an early contact inhibition mechanism, so they stop dividing much sooner than you see in humans or mice.

Interviewer - Chris Smith

Does this mean that we could apply the same technology to people with cancer, could we use the same strategy as an anticancer method?

Interviewee - Patrick Walter

The researchers are actually quite hopeful. So, what they discovered was that a particular enzyme is responsible for producing this extra large hyaluronic acid. They also discovered that in the naked mole rats, other enzymes were down regulated that actually degraded this hyaluronic acid. So there's two possible mechanisms, two pathways there to attack. You might then get humans to produce more of this large protein or to down regulate the degradation of the hyaluronic acid and thenceforth you'll be able to stop cells proliferating, with any luck.

Interviewer - Chris Smith

The obvious experiment to do would be to take that enzyme and make a mouse which expresses that same enzyme, so you would have a mouse which was the rodent equivalent of these naked mole rats. With that would you anticipate to have a similarly low rate of cancer, why haven't they done that?

Interviewee - Patrick Walter

What they've done here is they've showed the particular mechanism, so, I'm sure they'll be taking it on from there into be a mouse model.

Interviewer - Chris Smith

Would not the best thing be to put the gene into a mouse because then one would expect you would get a mouse that would have a very low rate of cancer if what they're saying is correct?

Interviewee - Patrick Walter

Yeah. I mean if they can get into a mouse and get this working, there's no reason why you won’t be able to see a cancer free mouse. I think that is the logical next step for them.

(4:42 - Thalidomide teams-up with turmeric to kill myeloma cells)

Interviewer - Chris Smith

Well, let’s watch this space. Thanks Patrick. Sticking with cancer though, Dan, turmeric is known to have antioxidant properties, it can also stop Alzheimer's disease up to a point, so does thalidomide. You've got a story about researchers putting the two together trying to get the best of both worlds.

Interviewee - Daniel Johnson

Yeah, cancer researchers have combined curcumin - that's the bright yellow pigment that you see in your turmeric spice, which gives it its colour - with the infamous drug thalidomide which you mentioned, to create compounds able to kill cancer cells.

Interviewer - Chris Smith

How did they join the two together?

Interviewee - Daniel Johnson

Through a variety of processes; they were looking at these hybrids because they can offer better ways of dealing with cancers. It’s often synergistic, which means the two molecules will contribute to something that's greater than being separate but they use a variety of different systems sometimes ester linkages, things like this.

Interviewer - Chris Smith

So, they jam those two molecules together, so you have this hybrid curcumin and thalidomide molecule. How did they test it, how did they show that it’s good news?

Interviewee - Daniel Johnson

They tested it on a variety of different cells taken from multiple myeloma, so the cells that you would see in the cancer of myeloma, and they tested its destruction rate of these cancer cells. So the point is that they made a lot of different hybrids and two in particular showed very good results in those tests.

Interviewer - Chris Smith

Why those two?

Interviewee - Daniel Johnson

They don't exactly know yet. Obviously when they were putting this together, they tried to keep the particular part of the molecules which do the work that you want the drug to do but they think that these two were the best.

Interviewer - Chris Smith

Do they know how it works? Why it’s having this cancer killing effect?

Interviewee - Daniel Johnson

There are a variety of theories. Thalidomide obviously inhibits new blood vessel growth which is one way it destroys the tumour and there's been lots of research into curcumin. But the scientists think with this hybrid that is to do with the generation of reactive oxygen species which then somehow inhibit the tumour growth.

Interviewer - Chris Smith

So, the drug promotes the formation of reactive oxygen species and this is what has a deleterious effect on the cancer cells.

Interviewee - Daniel Johnson

Yes.

Interviewer - Chris Smith

Any progression towards trying this in vivo yet, I presume this is stuff done in a dish isn't it?

Interviewee - Daniel Johnson

Yes, it is, yeah. I think it’s something to look at in the future. What the scientists say themselves is that they've looked at all these hybrids and they found these two that are showing very promising results, so that could be an avenue for doctoring and messing around to find the perfect hybrid.

Interviewer - Chris Smith

Dan Johnson. 

(7:23 - The ascent of molecules)

Fossils now, but not dinosaur footprints or even aminides but biological fossils. There are structures inside our cells that have hardly changed in nearly 4 billion years, which means they can reveal tantalizing glimpses into the past that we came from, Loren Williams.

Interviewee - Loren Williams

Well, the question we're asking is: can we use extant biology, that means the biology we see around us, can we use that biology to drill down and understand ancient biology. And by ancient biology I don't mean dinosaurs. Dinosaurs were yesterday as far as we are concerned, I mean, the biology at a very primitive state, biology before photosynthesis, before oxygen, basically the biology that came very, very soon after the origin of life.

Interviewer - Chris Smith

So, this biology of billions of years ago, isn't it?

Interviewee - Loren Williams

Yes. Biology of 3.8 billion years ago.

Interviewer - Chris Smith

Now, if we take dinosaurs as an example, they're relatively easy to study - as you said, they're a bit yesterday - because we can find their remains, how can you study something as intangible as biological concepts that are 3.8 billion years old?

Interviewee - Loren Williams

It’s really ironic, if you think about dinosaurs, 200 million years ago, it is a blink of an eye as far as story of life on Earth. We can look around us and we can see fossils, physical fossils of dinosaurs which are basically mineralizations of dinosaur bones. But in biology, biology itself actually is a better preservative of information about ancient biology. What I mean is that we have sequences in us and bacteria and in the world around us that are much older than any mineral fossil. We have things that are very well preserved on a molecular level that go back to a billion years back, that go back to 3.8 billion years ago.

Interviewer - Chris Smith

So, molecular fossils in other words.

Interviewee - Loren Williams

Molecular fossils, yes that are exact replicas of molecules that were here 3.8 billion years ago. So we have a really good fossil record of ancient life, it’s just that the fossils are molecules.

Interviewer - Chris Smith

Well, let’s take the ribosome then, which is something that your group spends quite a bit of its time looking at. What is that revealing about how life got started?

Interviewee - Loren Williams

Yeah, the thing we know about the ribosome, number one is that it is transmitted by what we call vertical processes: that means it goes mother to daughter, or mother to son. There's other things in biology, especially metabolic processes, that go horizontally. For example we have gained our metabolism from bacteria, we didn't inherit it from our ancestors the way we inherited our ribosomes, it was transferred what we call horizontally. So the ribosome and the translational system in general was transmitted by vertical processes. That means it allows us to drill back very far in time because we have that direct pathway of ancestry. And so, what it means is that if I compare my ribosome in a eukaryote, to the ribosome in a bacterium, I know that the bacterium only inherited their ribosome from their ancestors, I only inherited mine from my ancestors and so the similarities between my ribosomes and the bacterial ribosomes go back to our common ancestors, the common ancestors when bacteria split off from Achaea which ultimately split off into the Eukarya.

Interviewer - Chris Smith

What is the molecular fossil that's in the ribosome that makes it valuable for that because if it’s a simple structure, which I'm sure it’s not then it would very readily change or adapt and that past history would be lost. So, I'm presuming that there's a very rich molecular history in the ribosome which is enabling you to do this.

Interviewee - Loren Williams

There are parts of the ribosome which are basically exactly conserved in everything alive and what that means is that that part of the ribosome has not changed over an evolutionary period of many billions of years, it is the most permanent object in the known universe.

Interviewer - Chris Smith

Million dollar question then, because those are pretty strong words, why?

Interviewee - Loren Williams

So, I can use the analogy of an operating system of a computer. Let’s say I gave you a computer and I said you can't turn this computer off. I may say for 10 years you have to use it for a word processor, then you have to use it for air traffic control then you have to use it for some other purpose, but you can never turn it off. So, you would be able to change the monitor, you'd be probably be able to add or take a hard disk drive, you could do a lot of things to the computer but…

Interviewer - Chris Smith

If it’s running Windows it probably turns itself off within about 5 minutes!

Interviewee - Loren Williams

I would tell you, well no…

Interviewer - Chris Smith

But I detract, carry on...

Interviewee - Loren Williams

I have a friend who works for Microsoft, so I have to be careful, but yes I would tell you to get a Unix machine to start with, get a computer with a good operating system. But anyway one thing you cannot do to the computer is you cannot alter the operating system, you cannot keep the computer going and change the code or alter the operating system. And the reason is pretty simple, you can understand that there are so many things that depend on the operating system and there is so much interdependence there that if you alter it, all kinds of catastrophe will happen. And that's a really good analogy for biology. You can say ‘what is the operating system of biology?’ and the operating system is the thing that is untouchable, that even though there is incredible evolutionary pressure to do all sorts of things, but still there's some parts where you can't touch that. And that is the ribosome and the translational system because too many things depend on it and it’s catastrophic. So, it always just layers on things on top to make it work.

Interviewer - Chris Smith

So, now you're beginning to delve into the ribosome this way, what sort of secrets is it surrendering about how we think then life got started or what must have been the origin of life?

Interviewee - Loren Williams

Well, one thing about the ribosome is that the oldest, most ancient, highly conserved part of the ribosome has no protein. So that the ribosome is telling us, its core functionality is older than protein. You can say the ribosome gives us at a molecular level a truly ancient, a really ancient biology that is older than proteins. These are biological molecules that are older than the biology that we know so that's speaking to us from an ancient, ancient biological system. You’ve got to be excited by that, I think.

Interviewer - Chris Smith

Loren Williams. He's at the Georgia Institute of Technology.

You're listening to the Chemistry World podcast sponsored by Waters, with me Chris Smith. Still to come: what colour was archaeopteryx? Scientists have used x-rays to find out, as we’ll hear in a minute. And why E=mc2 means mercury is a liquid.

(14:32 - An end to chasing molecules that were never there?)

Before that, is this chemical structure correct? When researchers want to make a new molecule, they also make some predictions about what its nuclear magnetic resonance or NMR fingerprint might look like. Then, they go hunting for that fingerprint to confirm they've made the right molecule. But what if the NMR prediction is wrong? What ensues could be a fruitless search and numerous wasted experiments trying to track down something that doesn't exist. Now there's a solution, Jen.

Interviewee - Jennifer Newton

So this is a strategy using artificial neural networks to analyze NMR data and it tells you if a structure you've proposed is incorrect.

Interviewer - Chris Smith

Who's done this and what exactly have they done?

Interviewee - Jennifer Newton

So this is work done by Ariel Sarotti from the Rosario National University and the work is published in Organic and Biomolecular Chemistry. He used artificial neural networks, he showed that if you have experimental NMR data, and use crude desktop computational methods to generate a structure, you take the structure and have some computational NMR values from the structure. So Ariel has made a spreadsheet. And so if you take the experimental NMR values, put them into the spreadsheet along with the computational NMR values the spreadsheet would tell you if your structure is incorrect.

Interviewer - Chris Smith

So, you make a model of what you think you're trying to create, you put the values that you would expect from that model into the spreadsheet along with what you think you've made and it will then say whether or not this prediction you've made is an accurate one or not so then you know whether or not to go ho hunting for that molecule.

Interviewee - Jennifer Newton

Exactly so this method would tell you if your structure is incorrect, but it won't tell you if your structure is the correct one.

Interviewer - Chris Smith

Why not, why can't it do it the other way?

Interviewee - Jennifer Newton

It can't do it at the moment but that's something that he hopes to work on in the future so you can tell if you've got the correct one.

Interviewer - Chris Smith

How did they train this in the first place so that it knew what to look out for?

Interviewee - Jennifer Newton

So, he took a set of 200 molecules where they had the correct NMR values and they also had some incorrect values and they trained their artificial neural networks. So, an artificial neural network is based on the brain, where it can learn from past mistakes so it’s capable of machine learning and pattern recognition.

Interviewer - Chris Smith

In what way would chemists find this useful?

Interviewee - Jennifer Newton

The pharmaceutical industry, I'm sure, would find it very useful. It would save them a lot of time and money if they could decipher at a much earlier stage if the structure they were pursuing was the wrong one, so they know that they have to stop.

Interviewer - Chris Smith

They might for instance be expecting to make shape, or NMR spectrum, X. If that's a mistake and they go hunting for it, they would never find it and waste a lot of time trying to make something that does have the correct spectrum. Whereas this would pick that up at a very early stage and say you've made a mistake.

Interviewee - Jennifer Newton

Exactly. And you only need basic computational software to use it, you need the spreadsheet and you need no experience with artificial neural networks at all. So, this spreadsheet is completely accessible for all chemists.

Interviewer - Chris Smith

Thank you very much Jen.

(18:25 - Plumage pattern revealed in 150 million-year-old bird)

 Let’s go back about 150 million years, I think, to the time of Archaeopteryx which is a dinosaur, which was the earliest ancestors of birds. Now actually scientists reckon they can tell what they looked like in terms of their plumage patterns.

Interviewee - Daniel Johnson

Yes exactly and this team of scientists have discovered what they think are patterns in their feathers which obviously has huge importance. Darwin was interested in birds and their patterns and how that affected their evolution.

Interviewer - Chris Smith

Who's done this and where are they?

Interviewee - Daniel Johnson

The group is lead by Phillip Manning from the University of Manchester and they're collaborating with the US Department of Energy, specifically the Synchrotron. But what they've done is that they've used the synchrotron to fire x-rays, high energy x-rays at the samples and these x-rays pick up whether there are trace metals on the sample, such as copper. Now this copper was chelated to eumelanin at that time, so if they find this copper...

Interviewer - Chris Smith

Eumelanin being the dark pigment that would give feathers, and hair actually, its black colour?

Interviewee - Daniel Johnson

Yes, exactly, and if they pick up this copper, they know that there has been eumelanin on the feather.

Interviewer - Chris Smith

So, effectively the feather may not exist in the fossil anymore but some of the chemistry that went with the feather is still there in the form of this copper that was glued onto the melanin and that's what they're seeing.

Interviewee - Daniel Johnson

Exactly, it’s a trace of the pigment. Some work has been done before on this but not in so much detail and the point is that they have seen higher concentrations of this copper, this trace copper around, the outside of the feather. So they have discovered that there's a pattern whereby the tips and the outsides of the feather are darker.

Interviewer - Chris Smith

But they presumably can't say exactly what colour it would have been because we have no existing Archaeopteryx to compare it with.

Interviewee - Daniel Johnson

No, No but it’s thought that eumelanin is usually a brown or black pigment, so they think it’s nothing too bright. But it’s a really interesting point, especially since Archaeopteryx is this kind of poster boy of the evolution, it stands on the bridge between reptiles and birds. So, any evolutionary traits that you can see that have huge consequences down the line.

Interviewer - Chris Smith

How does the synchrotron radiation come into the story? How did they use that to see where the copper is?

Interviewee - Daniel Johnson

It’s the high energy, I believe, that the synchrotron provides. The energy of the synchrotron is such that it can provide these, I believe the quote from the man himself was ‘millions of times brighter than the Sun’, so it was an extremely energetic beam of x-rays fired at the sample. The main point is that it’s non-destructive, because there are only so many samples of this Archaeopteryx.

Interviewer - Chris Smith

Just a handful, worldwide aren’t they?

Interviewee - Daniel Johnson

Yeah, only eleven ever discovered and they're of such cultural importance and scientific importance we can't afford to damage them.

Interviewer - Chris Smith

You certainly wouldn't be popular if you destroyed an Archaeopteryx but at least you know what colour it used to be, thank you Dan.

(21:39 - Animal pharma)

If you make a chocolate cake definitely don't give any to your dog, because dogs can’t break down the theobromine in chocolate, in fact once single chocolate bar contains potentially fatal dose. Similarly a paracetamol will kill your cat, but your pet rat will be fine. So how do we make and safely assure new drugs for animals? Kevin Greenlees oversees this process at the FDA's Center for Veterinary Medicine in the US.

Interviewee - Kevin Greenlees

Animal drugs are in many ways regulated very similarly to human drugs. Whether they're intended for use in your pets, dogs and cats, or whether they're intended for animals that are part of your food supply, or whether they're intended for animals that are used to produce some other product that goes into the industry. The way that they're regulated, the details differ a little bit because clearly if a product is intended to go to an animal that is itself going to as food, then you have to evaluate the safety of the residues of that drug for the human consumer. Whether it was intended for an animal like that or for a companion animal like a dog or a cat, then you also have to look at the same things that you would like at in the human medicine: is the product effective for its intended use? Is it safe to the animal that is being administered to? And in addition to that, we have to look at the potential impact of having approved that product on the human environment, all of which is part of human medicine as well.

Interviewer - Chris Smith

When we talk about human drugs, we're usually saying that the test tube to needle time for an agent can be 10 years or so and the price tag might be 10 billion, is it similar for animals?

Interviewee - Kevin Greenlees

The timeframe can be very similar but they cannot afford the kind of budget that is available for human medicine, so you're looking at instead of 10 billion, you're looking in the millions.

Interviewer - Chris Smith

I suppose, one another difficulty with the veterinary market is that there's only one breed of human, really in the grand scheme of things, but if you look at the dog, for example, there are some dogs which, just by virtue of their breed happen to be more susceptible or sensitive to certain agents than other dogs.

Interviewee - Kevin Greenlees

Yes and it gets even more complex than that because when you approve a product for humans, you have the advantage of only having to look at that species, humans. But humans themselves are very different and when you look at animal medicine, not only do you have all those different species, which produce very great differences, and not only can you have great differences within breeds as you explained in dogs, you can also have a group which is very, very similar. So if you're looking at just one breed of dogs and one line within that breed, you can have animals that are extraordinarily similar which doesn't usually happen in human medicine. The other problem is that because you have such a wide base, you have everything from rats to elephants, literally, as potential patients, if you think about it, the opportunity to have products approved in all of those species for all the indications are actually very limited. So, many times a veterinarian has a set of approved products that they can deal with and look to those as their first choice but they may not have the product that they need directly approved for that indication or that species and they have to look and see what other approved products are there that they might be able to use. It’s called extra label use and they use it based on their professional judgment and their professional knowledge to say that this is a product that I could use under these circumstances as an individual medicine for that patient who has come in.

Interviewer - Chris Smith

And what about the question of what happens to antibiotics? Because these are used extensively in agriculture and we know that they're going to, therefore, have an impact on organisms which live within farm animals and inevitably organisms that live in the environment that could ultimately then share their genetic know how with organisms that live in on and infect us.

Interviewee - Kevin Greenlees

So, that is in fact part of the approval process to look at that and we're actually to look at it in two different ways. One is the environmental review which I just mentioned but that is also part of our human food safety review where we actually do a risk assessment on the potential for the use of the antibiotic or antimicrobial in an agricultural animal, having an effect on antimicrobial resistance. That's part of the actual review and we found that conditions of use posed an unreasonable risk, we would not allow approval of that product.

Interviewer - Chris Smith

But one could argue that we're seeing unprecedented levels of antimicrobial resistance and we've got quite good evidence that this has direct origins in the environment. I mean, people are showing their gene modules which are 100% overlapping with the same genes cropping up in hospital acquired and hospital diagnosed infections showing that one must have begotten the other. So what is being done to make sure that this doesn't get out of hand?

Interviewee - Kevin Greenlees

Well there are number of initiatives that are underway. There are very strong initiatives reaching out to the medical community, both the human medicine and veterinary medicine to practice what is known as judicious use where you actually look very carefully at the use of the antibiotic whether it is in animals or people. Because to be perfectly honest, it doesn't really matter what we're using it for, all uses of an antibiotic are likely to encourage bacteria to develop resistance because they're very good at doing that. There also are efforts to try and minimize the use of antibiotics in United States for uses that are not therapeutic in food producing animals. So, in the agricultural world, the uses are restricted to those cases where you really need them. That evaluation I spoke of as part of the food safety evaluation looks to the criticality of that antibiotic for human medicine and factor that into part of the evaluation as well, so there are a number of things trying to get a good handle on that and come to grips with it.

Interviewer - Chris Smith

Kevin Greenlees.

(28:40 - Relativity behind mercury's liquidity)

Why is mercury a liquid? Sounds a pretty simple question, but the answer is actually down to special relativity, Patrick?

Interviewee – Patrick Walter

That was being written in text books for ages that mercury is liquid but until now, it seems there's been no actual evidence for why this actually is, so Peter Schwerdtfeger at Massey University in Auckland has shown that mercury is liquid due to relativity.

Interviewer - Chris Smith

Why did people say, then, if they had no clue - why did they say it was a liquid? I mean obviously it is, but what arguments did they advance about why it might be liquid?

Interviewee – Patrick Walter

Okay, so in the past, relativity or special relativity has been postulated since the late '70s apparently that this is the reason why mercury is liquid. So, the reason why mercury is actually a liquid comes back to relativity. So special relativity, It’s Einstein's famous formula, E=Mc2. So this is energy equals mass times the speed of light squared. So this formula links mass with the speed of light. So, as you go down the periodic table, the elements get heavier and as they get heavier the electrons get drawn towards the nucleus because there are more and more protons, there's more and more attraction between the protons and electrons and as the electrons get drawn in, they have to move faster and faster to avoid getting sucked into that nucleus. So in some of the heavy elements like gold and mercury, they move so fast that they are reaching relativistic speeds, light speeds basically. And what this means is that some electronic orbitals are stabilized while others are destabilized. This varies from element to element but in the case of mercury you get a lot of stabilization going on. So the mercury atom becomes very isolated. It’s a very inward looking element, it doesn't want to share its electrons so it just keeps to itself and what you get is just van der Waals reactions between the mercury atoms.

Interviewer - Chris Smith

When we talk about a metal, most chemists tend to talk about a series of positive ions, those being the nuclei, in a sea of delocalized electrons, and that's why metals are really good conductors. So what you are saying is that owing to these relativistic effects, you end up actually with the sea of isolated atoms?

Interviewee – Patrick Walter

Exactly yeah, so you have these isolated atoms and just van der Waals bonds between them and this kind of gives them the liquid structure.

Interviewer - Chris Smith

Because they just flow around each other.

Interviewee – Patrick Walter

They just flow around each other.

Interviewer Chris Smith

Still conducts electricity really well though, mercury, doesn't it? So does that mean that some of the atoms have adopted this configuration, while others occasionally don't and so that's why it’s still a good conductor?

Interviewee – Patrick Walter

They're still like liquids so they're still close together, so just as liquid metal will conduct, there's no reason why liquid mercury shouldn't, so still get the mercury atoms close together to each other, close enough obviously for electricity to pass along.

Interviewer - Chris Smith

How did they prove that this very elegant explanation is what's really going on for the mercury?

Interviewee – Patrick Walter

So what they did was they performed some very complex calculations and ran them through computer models. So once they put this program together they showed that without these relativistic effects they were modelling, without the electrons moving at the speed of light, mercury would have a melting point of 82 degrees Centigrade rather than its actual melting point, which is about -39 degrees Centigrade.

Interviewer - Chris Smith

Does the same physics and chemistry also apply to other members of the periodic table that are metals that melt with a very low temperature? I'm thinking things like gallium. Victorians knew that if you made a teaspoon out of this you could play a trick on people that they'd stir their tea and the spoon would vanish. So, is that what's going on in there too?

Interviewee – Patrick Walter

I'm not so sure about gallium whether it’s down to relativistic effects or not, but there’s certainly a good possibility because it is a bit of an outlier compared to its neighbours in the periodic table.

Interviewer - Chris Smith

Well, if any canny Chemistry World listeners know whether or not gallium does melt at low temperature due to relativistic effects, then do let us know. 

(32:52 - Students develop antivenom in high school lab)

In the meantime, toxins. And Jen, an amazing story from a high school in America about neutralizing toxins in a thoroughly new way.

Interviewee - Jennifer Newton

Yeah, this story is really interesting because, it’s about an US high school teacher and nine of his students who have made nanoparticles that can neutralize venom from one of the most dangerous snakes in Africa.

Interviewer - Chris Smith

Which snake, out of interest?

Interviewee - Jennifer Newton

It’s the Mozambique spitting cobra which is the most common cobra in the Savannah regions of tropical and subtropical Africa and when it’s threatened, it will stand up and it can spit its venom up to eight feet.

Interviewer - Chris Smith

I've seen them on television doing this, and people often put sunglasses on to avoid getting the venom in their eyes. What did this school group do?

Interviewee - Jennifer Newton

They made the anti-venom in a similar way to making paper mache where a balloon is used as a template and you cover it in paper strips and once the paper is dry, you pop the balloon and take it out. So in this case, the snake.

Interviewer - Chris Smith

And that leaves a balloon shaped lump of paper mache, doesn't it?

Interviewee - Jennifer Newton

Exactly. So in this case, snake venom toxins were used as a template and added to a mixture of acrylamide monomers which then polymerized around the toxin. The toxin was then removed and this leaves a polymer in a shape that's complementary to the toxin.

Interviewer - Chris Smith

So, let me guess, the proposed mechanism is that you've then, you get something which is like a perfect key in a lock fit, so if you added those particles, then the toxin molecules, the venom molecules would go straight into the holes and get locked up in there.

Interviewee - Jennifer Newton

Exactly, it traps the venom. So they tested the anti-venom by adding it to pig blood cells with the snake venom, so normally the venom would rip the blood cells apart and destroy them but with the anti-venom there, it bound to the venom and stopped this from happening.

Interviewer - Chris Smith

So, it’s an in vivo effect that still needs to be done but it appears to be working in vitro.

Interviewee - Jennifer Newton

So, at the moment they've only tested this on these pig blood cells and they would really like to be able to take this further, get some other group excited and take it into experiments in animals.

Interviewer - Chris Smith

Do you think it would work for other types of venom and toxin molecules as well?

Interviewee - Jennifer Newton

There's no reason why it couldn't work on any toxin from any venomous animal.

Interviewer - Chris Smith

Why would the venom molecule like going into this shape that’s it complement, like a hand in a glove, more than binding to the thing on the cell or whatever the target is that it would normally be programmed to attack in the victim?

Interviewee - Jennifer Newton

They already know the shape of the toxin and they designed a mixture of acrylamide monomers based on those that would most favourably interact with the toxin, looking at the electrostatic and hydrophobic interactions. So, they designed this mixture to bind on to the toxin really strongly.

(35:53 - Trivia - How did the birth of a royal prince further the study of anaesthetics in the UK?)

Interviewer - Chris Smith

What a wonderful story.

And let’s finish now, are we going to have to jump on the bandwagon Patrick?

Interviewee - Patrick Walter

Certainly we're jumping royal bandwagon, so congratulations to the Duke and Duchess on the birth of their baby boy which brings us to this month's trivia, which is: how did the birth of another Royal prince further anaesthesia use in this country? It turns out that in the late 1840s, John Snow, later of cholera outbreak fame, he was experimenting with anaesthetics. I don't know if he was doing it personally...

Interviewer - Chris Smith

Recreationally?

Interviewee - Patrick Walter

That’s right. Recreational experimentation with ether and chloroform! But other doctors at that time were rather sniffy about it, I suppose you could say. They didn't really think much of using anaesthetics, that it was dulling pain and then you wouldn't know kind of how the patient was reacting. But in this case, John Snow got a call from Queen Victoria's doctor and this was asking him to come and help deliver her eighth child, this was Leopold. So he took some chloroform along and he dripped it onto a cloth that was draped over Queen Victoria's head and thusly we moved towards an acceptance of anaesthetics because where the royals lead as we know everyone else likes to follow. So I'm sure high society soon followed suit and anaesthetics were being given in birth and then it spread to just everyone

Interviewer - Chris Smith

And I think it’s fair enough to say we can expect quite a few Georges to be born in the next few years. Thank you Patrick and to the rest of the Chemistry World team this month who were Jen Newton and Dan Johnson and of course our guests, Kevin Greenlees and Loren Williams. The Chemistry World podcast is sponsored by Waters who are world leaders in innovative analytical science solutions. This program was edited and compiled by Meera Senthilingam and I'm Chris Smith from the thenakedscientists.com. Thanks for listening and until next time, goodbye.

 

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