Crystal Clear About Glass

Most of us succumb to an average of 3 coughs and colds per year. The main culprit in over half of cases are viruses called rhinoviruses and enteroviruses. When a symptomatic person sneezes, they spray out a mist of millions of these particles that drift about in the air waiting for you to breathe them in. Once they settle on the cells in your nose and throat, they invade, hijack the cells and transform them into virus factories; and then cycle starts all over again, making you feel awful in the process. But in a new study in the journal Nature Microbiology, Jan Carette and his team at Stanford University have identified a protein in our cells that these viruses rely on when they grow. And cutting off the supply of this substance halts the viruses in their tracks. So could this potentially pave the way for a cure for the common cold? Cambridge University virologist Ian Goodfellow took me through the results of the new study…

Ian - In this paper they've essentially identified a host protein that appears to be essential for a number of viruses that cause the common cold and enteric infections. When they’ve deleted this gene encoding this particular protein, the viruses are no longer able to infect cells.

Chris - How did they find the gene in question?

Ian - To identify the gene, they used a process to delete every single gene in human DNA.

Chris - Is that what, one by one? So they go through the entire genome, and one at a time disable one gene after another, and then test whether or not that disabled gene has an effect on the virus?

Ian - Exactly that. So you mutate every single gene one by one, then you infect them with the virus, and then you look for cells that survived. And these cells that survived are resistant to infection, and therefore have a mutation in a gene that is essential for the virus life cycle.

Chris - Right. So they identified a gene. What is that gene that they've found that seems to be so important, and do they know why disabling it has this effect on the virus?

Ian - The gene itself was called SETD3, it's a protein known as a methyltransferase. And they don't know exactly what stage in the virus life cycle it plays its role, but they know that in the absence of this protein the cells are largely completely resistant to infection.

Chris - They show that in the dish to start with, but would that work in a living animal? Because it's one thing to disable a gene and have a cell still thrive in a dish, but very different with a whole animal in which you are trying to do this.

Ian - This is one of the beauties of this particular publication. They've translated their observations from immortalised cells into a whole organism model. So they've taken a mouse model and they've inactivated this gene, and shown that when you infect these mice with these various viruses, they're completely resistant to infection.

Chris - And clinically, what's the relevance or use of this discovery? How could virologists now take this forward, and is it potentially a doorway towards - I hate the phrase - but a cure for the common cold, or at least some forms of the common cold?

Ian - So what this paper does is it really identifies a key whole-cell protein that's important for a whole group of viruses that cause a range of diseases. It isn't immediately like tomorrow we can all of a sudden develop a drug to this particular protein, but what it does is it says, if we find a way to modify the function of this protein then we probably have an effective way of treating, or controlling, or preventing the infection by these viruses. So it identifies SETD3 as an essential component in the virus life cycle. And if you can make drugs that target SETD3 you might be able to inhibit the virus replication.

Chris - Could the same strategy be used for other clinically relevant infections? Because colds are one thing, they're a nuisance, but they're not by any means the main way in which viruses bring down the human race.

Ian - Yes, exactly, and it's become increasingly common in virology now for individuals to use this precise approach, where you use CRISPR-Cas screening to identify host proteins that are essential in a virus life cycle, and then to use that as a potential target for therapeutic approaches. And just recently we've undertaken some work on a related family of viruses known as noroviruses - that cause gastroenteritis - to do precisely the same type of approach. And when we've done that we've done a CRISPR-Cas screen to identify a single protein known as G3BP1. This protein is absolutely essential for both the mouse norovirus replication and for human norovirus replication. And we hope that in the future this will enable us to develop a potential therapeutic approach for the control of norovirus-induced gastroenteritis.

Chris - Viruses are notorious for being able to change their genetic makeup; they mutate or change. If we did work out how to use these vulnerabilities, to make drugs to block them, is there not a high likelihood that pretty quickly, the viruses would fight back by just adjusting their modus operandi to bypass whatever block we put in the way?

Ian - This point about the development of resistance to drugs is a real key factor when we consider developing any sort of therapy for viruses. And as you say, viruses change very rapidly. But when we target a host protein it's very, very difficult for the virus to change to overcome that. It's not impossible, but it's much easier for a virus to develop resistance to drugs that target viral proteins than it is for it to develop resistance against drugs that target the host.

This week, Peter Bridger has been in touch about an interesting experiment involving gravity and a gold bar, and Rob Clements is closing to completing a truly iconic challenge...

Chris - We’re onto the mailbox now, this is the part of the program where we read out your correspondence. Now Peter Bridger has got in touch from Australia, and he sent us a very nice letter. It went actually all over the place, before it finally arrived to us. I'm sorry we're coming to this slightly late Peter, but he's been in touch telling us about the time that he spent here in Cambridge, because he was originally working with centrifuges, and this got him thinking and wondering about gravity, and so he's proposed an experiment and he says: Well could you take a gold bar all over the world and measure the gravity that it feels at the equator compared with the poles. And the rationale behind this idea is that because the equator is spinning a lot faster than the poles are, then the bar ought to weigh a bit less there apparently, because it's not being flung out into space at the poles in the same way as is at the equator. Adam is that a good idea?

Adam - I think it is. I mean the first thing to say is; we're not going to get flung off the planet like some horrifying roundabout, gravity is much much stronger than any spinning the Earth does. But it's a very good experiment because it's one that's been done a lot throughout history, and they've found but in different parts of the world gravity actually is different, and they found that it can waver by up to about 0.5% of how heavy something is. So in cities like Kuala Lumpur or Singapore which are by the equator, something is half a percent lighter than it is in places like Oslo because that's at the poles.

Chris - Pretty extreme way to go on a diet though isn't it? To go down to the equator just to lose a little bit of weight.

Adam - I mean if that's what you gotta do to make yourself feel better about scales that's what you got to do.

Chris - So it has been done?

Adam - It has. Yes. Not only have they gone to these places with weighing scales because that's how you measure how much something weighs we've had satellites in orbit measuring these things.

Chris - That's GRACE isn't it? The pair, or brace of satellites that actually whiz round the Earth and measure how fast one's accelerating relative to the other, because that's how they weighed the ice on Greenland to know what the rate of ice retreat was.

Adam - It's the Gravity Recovery And Climate Experiment is GRACE. And when one of them passes over somewhere heavy it gets pulled a bit ahead and then the other one catches up and that's how it measures things.

Chris - Thank you very much Adam. Meanwhile quick shout out to Rob Clements. Now he's in Nottinghamshire, and he's one of a very select band of brothers if I can put it like that because he's completed the audio equivalent of an ironman challenge, because he’s made it through our entire Naked Scientists podcast catalogue close to 1000 episodes going back to the very beginning. We’re one of the oldest and longest continuous running podcasts in existence so that's quite a feat. He has now reached August 2019, so Rob that red tape is in sight you're almost up to date, you're almost back in sync with the program. We're very intrigued to know if anyone else has managed a marathon like this, so if you're one of that band of brothers do let us know.

Chemically speaking, what is glass, and why is it so special? Chris Smith was joined in studio by Paddy Royall from the University of Bristol, to take us through the looking glass...

Paddy - Glass is an amorphous solid, and can be produced from many different materials, in the way that ice is a crystalline solid of water and sodium chloride is a crystalline solid and these are chemically different. Glasses can also be chemically different and are solids but they are amorphous.

Chris - But what actually chemically is the stuff that we call window glass and what atoms are in there?

Paddy - Silicon and oxygen. So it's two oxygens for each silicon, and that is one example of a glass. But there are many other materials that can also be made into glass. Examples include many organic molecules like ortho-2-phenol. You can even make a glass out of water. You have to try quite hard and cool it very very quickly. To make a glass, essentially what one needs to do is cool it down before the material has a chance to crystallise. So in principle more or less anything can be turned into a glass assuming you can call it down fast enough. Essentially what we call a glass is when you've taken a liquid, and cooled it down until the viscosity has become a million billion times greater than that of water, and one could do that in principle for any liquid.

Chris - Is it true then Paddy, that when you look at windows of old buildings, they're thicker at the bottom of the pane than at the top of the pane, because the glass is a liquid and over hundreds of years it has gently sagged and flowed downhill.

Paddy - I'm sorry. No it isn't. That is an old wives tale. The glass did indeed flow, but it flowed as the material cooled. So as we just heard glass is a liquid at 1,100 degrees Celsius, and it is during the cooling process from that temperature down to room temperature that the flow occurred. At ambient temperatures glass is every bit as solid as any other solid that one might encounter. So there is no meaningful flow or deformation of the material on the timescales of centuries.

Chris - From you as a scientist, what is the interesting glasses for you? How are you trying to study them and understand them better?

Paddy - The real question about glass as far as we're concerned in glass physics, is we don't really know what glass is. That might sound strange because one can simply look at it, but fundamentally we don't understand why these liquids become so viscous, they become a million billion times more viscous than water, as I said, but why does this happen? And the truth is that we just don't know. It may be that it happens because there is an underlying material which is known as an ideal glass, and that the transition to this underlying material may result in the liquid becoming very very viscous and us terming it a glass. On the other hand, it may simply be that the mobility, the amount the particles move, or molecules move in the liquid, simply becomes less and less and less. And so essentially there are two competing ideas. There are very many different theories but they boil down to these two competing ideas, that either the molecules somehow move less and less and less, or that there is some underlying transition to something called an ideal glass.

We don’t usually think of glass as particularly tough, much the opposite. But we can make our glass tougher, we can even make it bulletproof, but how? Chris Smith was joined in studio by James Perry from the University of Cambridge to explain some tough science...

James - So it turns out that the theoretical maximum strength of glass, if you could decide exactly where you are putting all of those atoms of silica and oxygen, is about a thousand times stronger than an actual lump of glass.

Brittle materials - and glass is a prime example of this - their defamation and their failure are largely driven by flaws, imperfections, and particularly cracks. So as you cool a material down it shrinks, so when you’re cooling your glass it shrinks down and the surface of it looks a little bit like a dried-up pond with cracks all over the place.

So cracks are particularly problematic in tension or if you bend the material. So if you take a plate of glass and you start to bend it, the outer edge is in tension and the inner edge is in compression. The outer edge, as you pull it, a lot of this force - a lot of the stress - gets concentrated at the very tip of those little cracks. So all of that force is concentrated on just one atomic bond, which eventually will pop open at a much lower stress than it would take to expand the whole thing.

Chris - It’s going to undo like a zipper, isn't it? It’s almost going to propagate down into the material. So once it gets started…

James - It doesn’t stop.

Chris - ...it’s going to accelerate.

James - Precisely, yes.

Chris - And you said something interesting, because you said, when it cools down you end up with the outside, it’s going to cool a bit faster than the inside and that's going to have the effect of making those pond wrinkles as you say because you'll get the outside being relatively stretched and the inside squeezed a bit.

Is there any way of intervening to change that then, so that we don't end up with the glass being vulnerable in that way?

James - Yes very much so. So if we go back to the 16th century there's a fun little thing that came across the Royal Society called Prince Rupert's drops. So if you take a blob of hot molten glass and drop it in a pool of water it freezes and it turns into essentially a tadpole. And that tadpole you can wack with a hammer on the head or you can even shoot a lead bullet at it and it won't do anything.

But if you just tweeze the tail with your fingers it will immediately shatter into a million tiny pieces.

Chris - Why?

James - So, skip forward a couple of years to the turn of the last century, and we realised that by cooling very rapidly the material - and for toughened glass now we use high pressure air instead of water - you cool the surface very rapidly and that cools, and then the inner bit cools much more slowly. But as it cools, it also reduces in volume and so it ends up pulling the outside edges in, leaving it in the middle in tension and the outside in compression.

And that stops a lot of those little cracks of the surface from opening up. Which means if you are then loading this toughened glass, then it's got to overcome the compression that it’s already under and then the tension required before it'll fail.

Chris - So why does nipping off the end break it?

James - This toughened glass that is used for things like shelves or anything else you might find in the house, that you don't want it to fall apart at the smallest knock. The problem is it will fail and will fail really quite catastrophically, because as soon as you break through that layer and you manage to tweak the tensile bit in the middle it pings apart.

So in the drop, the tail is so thin that that outside compressive layer is incredibly thin. And so you are firing these cracks right the way through of the tail up to the top. So the same kind of thing happens with toughened glass, in that when it smashes it pulvarises into thousands of tiny little cubes usually. Which in some applications is really useful because you don't end up with big pointy shards you end up with a pile of little ones -

Chris - Like a windscreen, you don't want to impale the driver, you want little bits of glass you can brush off?

James - Precisely. But that's not so useful if for example you want to be able to still keep that barrier intact after that initial impact.

Chris - In other words bulletproof glass, because you what you want the glass so that it will not fail in that catastrophic way across your whole windscreen and then somehow also be there as a defense against the next projectile. Because otherwise you could kill someone by firing two bullets, one to demolish the windscreen and it might fend off the first bullet, but if the whole thing smashes to pieces, you fire the next one and it goes straight through.

So how do we stop that? How do we toughen up glass?

James - Above a certain amount of force or a certain amount of stress, you are going to cause some damage you can't get away from that fact. So the trick then is to build your material such that a single impact of that amount of damage, isn't going to completely catastrophically destroy your material.

So you can do that by building up in layers. The first layer is glass which is very very strong. And so that will help dent the projectile and soften it up. So it goes from a very pointy tip to much flatter tip.

The energy of a bullet is not actually very much, but it's very focused on a small area. So if you can distribute it out then it's easier to slow down. And that's where the second layer comes in. So behind it you put a polycarbonate usually, a plastic, which is very soft but very tough. So it can deform an awful lot and absorb an awful lot of the energy in the process of doing so.

So what's an interesting thing actually to finish on is the fact that you can have one way glass. So if you have a layer of glass followed by a layer of polycarbonate, the glass flattens the bullet, the polycarbonate catches whatever's left. So what's a nice illustration of this is the fact that if you're firing in one direction you have the glass first, that flattens the bullet and then that moves into a polycarbonate layer, which then absorbs the energy. If however you're firing back in the other direction, you first punch straight through the polycarbonate layer, hit the glass layer, which then fails in tension and spawns lots of small fragments of glass.

Chris - So James Bond could  - if he wanted to - shoot some enemies from inside his car and his bullet proof glass windscreen will allow him to do that. But as long as he doesn't shoot first then he's going to fend off any of the enemies bullets!

James - Yes. So long as you put your glass in the window the right way!

Chris - Yeah. And does it really work? Can you really fend off a bullet with glass or is it there really to stop your windscreen demolishing with a stone or something but not a bullet?

James - Yes. So possibly a better description would be bullet resistant plastic with a bit of glass. So for a start these things are pretty thick. You can have them up to a couple of inches thick, and so obviously an awful lot of energy can be absorbed. It's worth pointing out that to use the James Bond analogy, I think it was Tomorrow Never Dies has a car where the bad guys are trying to break into it using hammers and bullets and absolutely nothing happens to the surface of the windows in the car. That is not the case, you will cause some damage relatively easily, but it will take a lot more effort to damage all the way through those multiple layers, in order to get inside.