A Punt down the Cam

03 August 2008
Presented by Chris Smith.

Science on the River - A Punt Down the Cam. The river Cam runs through Cambridge, past the colleges that have been home to influential scientists for hundreds of years. This week, we drift down the river, picking up key scientists as we go. We discover how petals attract pollinators, how carbon sequestration could call a halt to climate change and how ketamine could help us find the root of schizophrenic delusions. Also, we explore how evolved enzymes could make chemical reactions billions of times faster, and learn of the ultimate fate of the universe with Astronomer Royal, Professor Martin Rees. Plus, in Kitchen Science we see how sunlight can start a fire and mirrors can cause explosions!

In this episode

02:27 - Queens' College

A bit of history about Queens' college

Queens' College
with Sarah Castor-Perry

Queens' College was founded in 1448 by Margaret of Anjou, the wife of Henry VI and then re-founded in 1456 by the wife of Edward IV - hence it's name - and is one of only two colleges in Cambridge that have buildings on both sides of the river, the other being St John's. It also has the oldest building on the river Cam, the President's Lodge, which was built in the 15th Century.Mathematical Bridge

Here we're just about to go under Mathmatical bridge, which spans the river between the new and old parts of Queens'. It's the only wooden bridge on the Cam and it's held together by metal bolts. There's a bit of a legend about this bridge which often gets told to tourists, which is that it was originally built by Isaac Newton without any bolts at all. His design was apparently so perfect that the bridge supported itself. The story goes that some students took the bridge apart to see how it worked but then they couldn't put it back together again and had to resort to using metal bolts. Sadly this is not true, as the bridge was in fact first built 22 years after Newton's death! Although it has been rebuilt twice in the history of the college, it has always had these metal bolts in its design.

04:26 - Pretty Petals to Pull in Pollinators

Our first passenger, Beverley Glover from Queens' College talks about the hot world of flowers.

Pretty Petals to Pull in Pollinators
with Dr Beverley Glover, Queens College

Chris - We'd better pick up our first passenger and that is Beverley Glover from Plant Sciences. Welcome.

Beverley - Hi, Chris.Bumblebee - Bombus terrestris

Chris - I know I promised you a ride down the river Cam, a boat ride or a cruise or something and this is the best we can do. It's a low budget show!

Beverley - It's alright. We're quite used to it in Cambridge!

Chris - Now you're from Plant Sciences. What are you devoting most of your time to at the moment?

Beverley - Most of our work at the moment is about the surface of the flower, particularly the surface of the petals, and how different structures affect the way that the animals interact and collect its pollen and pollinate it.

Chris - How do flowers actually work?

Beverley - A flower is basically a bright advertising thing that says to animals there's something good to eat over here. The animal comes along looking for the reward, a good thing to eat, which is usually nectar and in doing so picks up a bit of the plant's pollen. It transfers it then to another flower and that way the plant gets fertilised and makes the seed.

Chris - What about the way the flower mechanically works? If you zoom in with a microscope and look at it in more detail what's actually there?

Beverley - Different flowers have different surface structures depending on what they're trying to attract. Different animals have different preferences. One thing we've looked at is if cell structures give grip so that if they're trying to land in high wind or at difficult angles they have something to get a grip on. Another thing we've been looking at is much smaller surface structures on a nanometre scale which affect the light that's being refracted and can give you iridescence on the flower.

Nectar guide visible to bees but not to humans
Mimulus flower photographed in visible light (left) and ultraviolet light (right) showing a nectar guide visible to bees but not to humans. © Plantsurfer @ wikipedia

Chris - So this will presumably mean that different animals or different insects can differentially see the flower and therefore it's more attractive to certain species than others.

Beverley - Yes, exactly. One thing that plants can do with structure is make sure they reflect very highly in the ultraviolet end of the spectrum which we can't see but many insects can. That makes the flower look much brighter to an insect than it is to us and makes it very attractive to them.

Chris - Why do insects want to see the UV? Where do they get that trait from?

Beverley - Not all insects have the same colour vision but bees which is what we mostly work with have three photoreceptors like we do but whereas we see the primary colours they see the ultraviolet, blue and green. The world looks very different to them and the flowers are adapted to how they want to look, not how we want them to look.

Chris - Is it anything to do with the fact that on a cloudy day UV can still come through and other wavelengths might not?

Beverley - It may well be. There is quite a lot of evidence that pollinator colour vision, or bee colour vision at least, evolved before flowers. It's as if the flowers have had to suit their colours to what the animals already had. It's not the other way around, the animals weren't going, "the flowers are red so I need to see red." That worked for them and then the flowers have adapted to suit.

Chris - Why would they need colour vision if there was no flower around to pollinate?

Beverley - That's a good question. One possibility was for the animals to see one another. A lot of insects are shiny in the ultraviolet or iridescent and that helps them attract mates or identify enemies and so on. Colour vision's important for seeing one another too.

Chris - Going back to the petals for a second. Those cells you're looking at to give grip - is that just all they do, they're sort of sticky to certain insects or do they have other jobs?

Beverley - No that's not all they do. I wish it was that simple. They also change the way the flower looks because they act as little lenses that focus the light on the flower to make it look brighter so we can see that effect. Animals can see it to; insects can see it too but it may not be very important to them. They can see it but they don't really care. They may also make the flower warmer by trapping heat. When they trap light they trap energy and so they make the flower slightly warmer. That to some pollinators in some environments maybe the most significant factor of the flower. It means that you don't have to spend as much energy warming yourself up to be able to fly.

Chris - You had a paper in Nature exploring that a couple of years ago.

Close up of hibiscus petal, probably Hibiscus rosa-sinensisBeverley - Yes, that's right. We showed that even a perfectly normal bumble bee at ambient temperature would prefer a warmer flower to a cooler one given the choice if the reward's the same in both. I think the difference these cells can make to how warm the flower is isn't very great for a flower on a sunny day or normal habitat. To pollinators that are foraging perhaps at dawn when the flowers are still quite cold, they might make enough of a difference to be significant.

Chris - Why does it make a difference? Why does an insect want to drink warm nectar?

Beverley - because it doesn't have to spend any energy warming it up itself. Bess have to spend some energy warming their bodies up just to be able to fly. It's like you having a hot drink. If the nectar comes in warmer then you don't have to spend as much energy warming it up.

Chris - Do all plants have these cells or is it just the preserve of ones that want to specifically attract certain insects?

Beverley - About 80% of plants have these flowering cells. We think that some are doing it for tactile reasons to give the animal a grip, some are doing it for other reasons. Some might be doing it for the effect it has on the flower looks. It seems to be an ancestral trait. Flowers seem to have had it from when they were first flowers. The plants that don't have it seem to have lost it That's actually something we're quite interested in is exploring those plants and why they've lost something  that seems to be so useful.

Chris - Plants that don't rely on insects to get pollinated, do they not have them?

Beverley - Most wind-pollinated plants have lost petals entirely so they don't have these structures which are only on the petals.

Chris - Looking beyond that where do you think this is going to go next? There must presumably be mutant flowers that don't have these cells and are they less fit? Do they grow less well?

Beverley - Yes. We have a mutant line of snap dragon (Antirrhinum majus) and also a mutant line of petunia that don't make these cells. I think they're perfectly fit and grow perfectly well in the greenhouse. If we plant them out we find they don't set as much seed. They don't get pollinated as well. They're not as attractive to bees. Those mutants have let us identify the genes that control this process. We can start to understand in the plants that have 'deliberately' lost them, the flowers that never have them, what's happened to those genes - where they've gone and why they're not working any more.

Western Honey Bees collecting pollenChris - So does this mean that if gave the plants more of these genes or made them express more of these cells you could make them more fertile, more fit and you'd get better yields off them?

Beverley - It would depend on the plant but that's certainly something we're thinking about. For instance, a lot of the members of the tomato family have lost these cells because of the way the flower is pollinated. The animals hat are attracted to them don't need them either for grip of for vision. The tomato itself hasn't lost them so one other thing we're interested at the moment is if we knock those genes out of tomato can we make it more attractive to pollinators to sew more fruit.

Chris - They're buzz pollinators, aren't they? In Australia they have to import bumble bees that can buzz at the right frequencies to make the pollen come out.

Beverley - Exactly. They're attracted to the anther which is the bright yellow thing that produces the pollen. That's what they're trying to collect to feed to their larvae, not the nectar out of the petals. The petals have become irrelevant and so we think for most buzz-pollinated species these cells have been lost because you're not trying to make the petals stand out. Tomato for some reason hasn't lost them so that's something we'd like to explore.

Chris - And just lastly, with a name like Beverley Glover working on Plant Sciences have you never been tempted to add the word fox in the middle so you could be a plant scientist called Beverley Fox Glover?

Beverley - You know it's funny. My husband makes that joke all the time!

The History of King's College
with Sarah Castor-Perry

Well on the right you can see the magnificent King's College Chapel, one of the most famous landmarks in Cambridge. This was started in 1441 by Henry VI, but then in 1455 the War of the Roses began, which took up all the king's funds as he had to pay for the army. The chapel wasn't finished until 1544 under Henry VIII and you can actually see on one of the walls a change in the colour of the stone where the building stopped and then was completed later.King

King's was originally set up for Eton boys, so quite an exclusive little club, and they only started letting in non-Eton boys in 1865!

12:57 - Capturing Carbon to Counter Climate Change

Carbon sequestration may be our best bet to offset the tonnes of carbon we pump into the atmosphere each year. Professor Herbert Huppert explains more...

Capturing Carbon to Counter Climate Change
with Professor Herbert Huppert, Kings College

Chris - Herbert, welcome to our punt. Welcome aboard!

Herbert - Thank you.  It's a little rock-y but it's fun sitting here.

Chris - Tell us - this carbon business, we'd like to think that weather like this isn't just the result of global warming.  What can we do to try and offset the carbon that we might be pumping out into the atmosphere?

Smokestacks from a wartime production plant, World War II.Herbert - You know we're pumping out 27 billion tonnes of carbon dioxide every year into the atmosphere.  It's been rising steadily since the beginning of the industrial revolution.  At the same time the global average temperature has been rising.  We're very concerned that it may be mankind putting this carbon dioxide into the atmosphere that not only is warming the atmosphere but is leading to terrible natural situations like Katrina and the droughts of Australia and the great heat wave of 2003 that killed so many people in Europe.  We'd like to see how we can either put less carbon dioxide into the atmosphere because we use less energy by burning less fossil fuels or by storing it in large reservoirs, porous reservoirs beneath the surface of the earth.

Chris - Some people say that the reason that you see a rise in CO2 with a rise in temperature as the water doesn't absorb as much CO2 when it's warmer. So if you warm the world up CO2 comes out and goes in the air.

Herbert - What is clear is that there is a good chance that because of the increase carbon dioxide that we're putting into the atmosphere the temperature is rising because of that.

Chris - What sort of strategies are there to try and get the carbon dioxide out of the atmosphere and also to prevent us putting it into the atmosphere in the first place?

Herbert - We could just be much more efficient in our energy use.  We don't need really to warm our houses as much as we do.  We don't need to drive individually around the country.  We could have to or three at a time coming into work.  There's no doubt that we could reduce the amount of energy that we use and be just as comfortable and just as happy.  As to actually what we would do with the carbon dioxide there are lots of suggestions.  The one that is most likely to work is to store carbon dioxide for at least ten thousand years in these porous reservoirs that are at the moment full of salty water.  But there are other suggestions for reservoirs such as coal seams, brown coal seams that are not attractive as far as mining them is concerned from a financial point of view.  They are also very porous and we could put it in there or depleted oil reservoirs. [There is] not as much storage space there available to us.  That's another possibility.

Chris - What are the mechanics of getting the CO2 there in the first place?

Macro photograph of bubbles in a fizzy drinkHerbert - The point is that normal carbon dioxide as we know it is a gas.  A gas takes up a relatively large amount of space compared to a liquid, sometimes up to a thousand times more.  We can compress the gas into a liquid by taking it down to a minimum of 800m but better somewhere between 1km and 2km.  You have to pump it down 1km normally where it becomes supercritical gas, it's called.  It's like a liquid, it has a density close to water but ¾ that of water.  Then it flows out into these pores in the rock really just like oil has been formed in pores.

Chris - How do you keep it there?

Herbert - The idea is that there will either be some totally impermeable seal, just as oil is sealed in reservoirs that's been made hundreds of thousands of years ago.  The other possibility which has been looked at but only from a theoretical point of view is to somehow play some game with the density.  The density of the liquid like carbon dioxide than that of the surrounding liquid and hence gets trapped.  That's a very dangerous business it seems to me because something could always go wrong and it somehow gets rather less dense and it comes to the surface.

Chris - Researchers in America who are looking at the possibility of putting the CO2 into water in the ground where it forms a dilute acid and then reacts with carbonates in the rock and you end up with the CO2 becoming almost like limestone.  It's sequestered as a rock.

Herbert - The question is how much energy is needed to do that, in the sense energy to make the chemical transfers.  My understanding is the energy is really quite considerable and also the process is very, very slow.  The thing we have to realise is we are putting in an enormous amount of carbon dioxide, 27 billion tonnes a year.  The biggest field projects at the moment have been sequestering something like a million tonnes every year.  We need something like a 100,000 such field stations.  We're a long way from getting there.

Chris - Also, where we're producing the CO2 isn't necessarily where we'd want to sequester it so there's the other problem, I presume, of getting it to where we want to store it.

Smoke of chimneys is the breath of Soviet RussiaHerbert - We're not going to transport it far.  My belief is that we'll try to do something with it where it's formed.  That's an important point because there's virtually no work done at all anywhere over the former Soviet Union, over South America, almost all of the southern part of Africa yet they produce a considerable amount of carbon dioxide.  At the moment no thought's been given to where you might sequester their carbon dioxide.

Chris - You mentioned parts of the Soviet Union.  A lot of that stuff is in what was permafrost which is now melting.  Organic matter is getting into water and very quickly getting digested and turning into methane and CO2.  I suppose there's that to take into account as well?

Herbert - Yeah.  That is a recent interest and people don't know exactly how much methane there will be and what the potential problems will be there.  That is something I think we need to look at very carefully as the Earth warms up and as you say much more methane can come out into the atmosphere.  This would not be direct anthropogenic input of methane but it is a consequence of anthropogenic effects.

Chris - Are you worried?

Herbert - No, I'm never worried.  Yes, the temperature may go up a little bit and yes, we may have a number of natural catastrophes but I'm sure we'll see our way around.

20:11 - Clare College

The history of Clare College

Clare College
with Sarah Castor-Perry

Clare is the second oldest college in Cambridge after Peterhouse, founded in 1326, although it doesn't look it from the river as the buildings you can see from here were built in the 17th and 18th centuries.Clare Bridge ball

What it's particularly famous for it its bridge. Clare Bridge is the oldest surviving bridge over the Cam and it has 14 stone balls along the top. 13 of these balls are intact but one has a wedge missing. One of the stories about this is that when the stonemason built the bridge, Clare didn't pay him enough so to spite them he took a slice out of the ball and took it away to even up his payment. Although this is a good story, the probable explanation is that the ball was repaired at some time in the past. It may have become loose on the metal rod holding it to the bridge, so a wedge would have been cut out to release the ball, then the ball turned on its side and a new hole drilled to re-fix it. The cut out wedge would have been filled with another piece of stone that since then must have fallen out and is presumably somehwere at the bottom of the river!

22:11 - Hallucinations and Delusions in Schizophrenia

Hallucinations and delusions resulting from schizophrenia are scientifically fascinating, but poorly understood and devastating for those affected. Dr Paul Fletcher is leading the charge...

Hallucinations and Delusions in Schizophrenia
with Dr Paul Fletcher, Clare College

Chris - Our next passenger is from Clare College and the Department of Psychiatry, Paul Fletcher.  Hi, Paul.  

Paul - Hi.

Chris - Welcome to our punt.  I'm sorry this was the best we could do.  It's a low-budget programme.

Paul - This is absolutely beautiful, don't worry.

Chris - What is it you work on?

Paul - I'm especially interested in schizophrenia and in particular the key symptoms of schizophrenia which are delusions and hallucinations.

Chris - What do they actually mean?

A fractal image, often used to represent hallucinationsPaul - They both relate to a very changed experience of the world.  An hallucination is when you hear something or see something that isn't really there.  A delusion is when you believe something that is quite extraordinary and probably untrue.  For example, an hallucination somebody might hear somebody talking to them, criticising them.  A delusion they might come to believe their neighbours are trying to poison them or control their actions.

Chris - Do people develop these delusions to explain the funny hallucinations they're experiencing then?

Paul - Some people think the experiences are abnormal and the explanation is a perfectly logical one for those experiences.  Other people think the experiences are not abnormal but people just reason in very different ways.  Other people think it's a bit of both.

Chris - What's actually going on in the brain of someone, say, who's having an hallucination or producing delusions like this?

A PET scan, illustrating of Schizophrenia's effect on the brainPaul - We know that people with delusions and hallucinations and other symptoms of schizophrenia have changes in the neurotransmitter, dopamine.  We know that it seems to be overactive although it's not entirely clear whether it's the receptors that are oversensitive or there's too much of the chemical.  We know that there are clues that this might be one of the prime suspects.  The real thing we don't know is how something as basic and low-level as that can translate into something as complex and human and social as a belief that someone's trying to harm you.

Chris - It's interesting because schizophrenia is quite genetic.  We know it runs in families but it also tends to come on much late in life even though presumably the genes that cause it are active from the time that you're conceived.  You don't get the disease until your mid-twenties.  In some cases a bit later, in some cases your seventies.  What's going on in the brain to suddenly make this come out when we're that bit older?

Paul - The mere fact that it doesn't tend to manifest in childhood, although it can, is probably giving us some vital clues about what the key problem is.  One possibility is that schizophrenia arises once the brain is fully matured.  It's only at the time that somebody has matured pathways in their brain that they're able to experience and express the sorts of symptoms that people with schizophrenia have.  Another possibility actually is that schizophrenia is present if you scrutinise closely at an earlier age.  In children it manifests in much more simplistic ways: motor abnormalities, speech abnormalities.

Chris - What about the association with various drugs because cannabis has been linked to people getting various psychotic symptoms, if not overt schizophrenia, hasn't it?

A cannabis cigarettePaul - A lot of people are pushing very hard to apply ever greater constraints on the use of cannabis because they believe strongly that it causes psychosis.  In actual fact if you look at the evidence we still don't know whether people use cannabis because they've got schizophrenia or they've got schizophrenia because they use cannabis.  One thing we do know is that the proportion of people using cannabis is much greater among people who are mentally ill.  It's certainly the case that that sort of disruption of a brain that's already vulnerable could precipitate an episode of these unpleasant symptoms.

Chris - If you look at the brains of people who have schizophrenia either with a brain scan or in post-mortem if you look at whole brains do you see any obvious differences with what we would call someone who's normal?

Paul - Up until the seventies people gave an unequivocal no to that.  In the mid-seventies somebody called Eve Johnson in Norfolk Park produced a ground-breaking paper which essentially showed that the ventricles which are fluid-filled spaces in the brain tend to be larger in people with schizophrenia.  This suggests that there's been some degree of shrinkage in the brain.  Most psychiatrists would accept that the brain is different in structure.  There's increasing evidence that it is different in the way it functions.

Chris - There's quite an interesting body of knowledge growing now that some of the genes that are associated with schizophrenia are associated with how cells migrate and move in the brain both during development and perhaps during adulthood.  We know that we continue to make new brain cells throughout life in certain parts of the brain.  Do you think this is something that you grow into?  You slowly accumulate enough cells as your brain ages and produce these new neurons that they make these pathways and perhaps connect up the wrong bits of the brains and disclose schizophrenia?

Paul - The very name schizophrenia itself means a splitting of the mind.  While many lay people would interpret that as a split personality what it actually means is the different faculties of the brain tend not to integrate with each other.  Functional brain imaging, which is what I use to measure whole brain activity in association with a series of challenges and symptoms, that's seeming to suggest that some of the core abnormalities may be manifest not as a failure to be active but as a failure of different regions to speak to each other.

Chris - There's a neurologist who works in Switzerland called Olaf Blanke who I talked to a few years ago.  He discovered when he was treating a lady for epilepsy that if he stimulated a certain part of the brain he could produce this out of body experience in this lady.  She was effectively experiencing her own body but the symptoms of someone touching that body.  She wasn't mapping onto that being her but she was thinking there was another person in the room with her.  Do you think there's a part of the brain that doesn't work properly in schizophrenia which would normally cancel out internally-generated things like voices and other kinds of things and tell you they're coming from you and that just doesn't work?  People think that they're something real.

fMRIPaul - Yeah.  There's good evidence that normally when your or I hopefully speak to ourselves in our mind we actually cancel out the auditory response to that.  It's as though there's a dampening down.  If we hear somebody else speaking then our auditory cortex is very responsive and active.  The suggestion is that in hallucinations it's treating internal speech as though it's external.  Therefore you hear what you say as though it's somebody else.  This would account for many of the phenomena of schizophrenia.  There is another very interesting symptom called a delusion of control where somebody feels that their own movements are actually produced by somebody else.  The same explanation might hold for this.  When I go to generate a movement I know what to expect.  I know the outcome of that movement will result in me being in a different position or my hand being in a different position.  If I fail to make that prediction then it may be that that comes as a surprise to me.  I could then interpret it as somebody else having made the movement.  These are interesting speculations and indeed there is growing evidence that this is may be the case.  I think Olaf Blanke's work is very interesting in that respect.

Chris - Finally, are we closer to helping people to lead a normal life once they're diagnosed with something like schizophrenia?

Paul - I think as we begin to understand the link between a chemical abnormality and a high level expression of a symptom in terms of processes that are very specific like this then we may be in a position to offer newly-targeted therapies.  An example of that is we're now finding we can reproduce some of the symptoms of schizophrenia with a drug called ketamine which has been widely used as an anaesthetic.  Maybe if we can target the same receptors that ketamine works on then we can begin to find new treatments, more acceptable treatments for schizophrenia.  In fact, only last year a paper came out suggesting that may well be the case.

Trinity Hall
with Sarah Castor-Perry

Trinity HallThis college was originally founded in 1350 to train lawyers to replace those who died in the Black Death of a few years previously.

30:30 - Enzymes for Extra-Fast Chemistry

Enzymes are the "amazing chemical machines" that make reactions happen billions of times faster than they would do anyway - and help keep your clothes looking as good as new....

Enzymes for Extra-Fast Chemistry
with Dr Florian Hollfelder, Trinity Hall College

Chris - Here's our next passenger.  Welcome aboard Florian Hollfelder, do step into our punt.  Come and have a seat.  Florian's a fellow of Trinity Hall college and also from the Department of Biochemistry.  You work on enzymes?

Laundry soaps in Jaffa flea marketFlorian - Yes.  Enzymes make reactions fast.  They're the ultimate green reagents.  Some food additives have enzymes.  Washing powder consists of enzymes and when you look at the chemistry these chemistries are very complicated and difficult to do in the lab.  Enzymes do it with rate accelerations which are large.  The numbers are so large that they hardly mean anything.  The accelerations are 1021, for example. That's a 1 with 21 zeros behind it.

Chris - That's how fast it makes a reaction got compared with if you didn't have the enzyme there?

Florian - That's right so if you look in the water the reaction would not be occurring at all, even after millions of years but when you put a bit of the washing powder in the suddenly proteins get degraded very quickly.  That's an amazing chemical machine and actually so amazing that we understand only a very small fraction of it.  We want to get farther into the unknown.

Chris - What you're basically saying is we want to be able to capture and use these molecules in the laboratory and also in industry to do things in a much cleaner, faster way that's more energetically favourable.  You're out there to find out (a) how these chemical reactions occur using enzymes in the first place and (b) how we can find better ones?

Florian - Yes.  That's right and the technical trick is to be so good at, first of all, making a mess and then be very accurate in finding one molecule out of billions of molecules that are useless. 

Chris - Do you mean you're making different versions of an enzyme when you say you make a mess you make lots of different forms of it?  Then you find the one which works best and then ask why?

Florian - Exactly.  We do it exactly like nature would do it.  Nature is imperfect and replicating the genetic blueprint, the DNA, we do that in the laboratory.  We use a reaction to multiply DNA molecules that makes imperfect copies.  We hope that they go in the right direction and that the difference makes a difference.

Chris - I see so you make a difference or an error in the DNA which changes the protein, the enzyme very subtly and then you ask has that difference translated into an enzyme that works better or worse?

Florian - This is exactly what we do.

Chris - What sort of reactions are you looking at?

Dirty RagsFlorian - We're looking at hydrolytic reactions.  Reactions where water is the reagent because they are useful.  They are useful in washing powders, in detoxification of pesticides and so on.  We have enzymes that are interesting because they do several things.  They're generalists.  They don't only do one thing well but they do several things very well.  In evolution this might have been extremely useful because often in nature you find that genes get duplicated and the best way of getting the new activity as soon as possible would be if the original enzyme had a small side-activity.  We call that catalytic promiscuity when an enzyme does not have only one partner but several partners with whom it can engage.  Often these are different chemistries that it can do.  That's why these promiscuous enzymes are a starting point for evolution.  You're more likely to uncover one clone for a new activity if you already had a little bit of it originally.

Chris - What sorts of things apart from washing powder are you looking at then?

Florian - For example, we are looking at phosphatases and some of the pesticides that have been put in nature in the fifties.  They are very slowly degraded and so having hydrolases that break them down completely in a bio-compatible way are useful for opening up brownfield sites again to nature.

Chris - Have you got any enzymes that you've identified that do that job well then?

DNA ModelFlorian - Yes.  We've found some enzymes that can be changed from one activity that is more or less useless to a more useful activity.  We're not quite yet in industrial applications but we can show we can at least.  The tricks we've developed in the technology were very important.  What we've learned in the process of that is that in principle you want to start of with a jack-of-all-trades that can do everything just not very well but it can do everything just a bit.  Then you enhance that background activity to get better.  If you start with something that is promiscuous, it interacts with everything, you have a much better chance to find a good clone, a good enzyme.

Chris - You say you make a mess and find out how it works later.  Do you actually ever work the other way and say right, we've now got a really good enzyme that's improved dramatically: now let's have a look at it and try and find out why?

Florian - Yeah so we then crystallise it.  We wait for it to form well-defined crystals, materials which you can diffract.  These are techniques that were developed in Cambridge in the 50s.  Now it's fairly standard that even an amateur like me with a good collaborator can start making crystals.  That then gives us insight in the inner workings of the enzymes.  We can pinpoint why we found it in the library in the first place.  That hopefully helps us to define a whole class of enzymes that are versatile.  In case you wanted and enzyme for a specific application we now know where to start.

Chris - I was going to say because presumably the endpoint for this will be you'll understand so much about it that you can just say either take it off the shelf you've made earlier or you'll be able to tweak something to add an activity - a certain chemical reaction or ability to do something well - to an enzyme that already exists?

Florian - Yes.  That's right.  The other thing which I think we haven't cracked quite yet is how nature can do it so efficiently.  Very often we find protein structures are very delicate.  They are a bit like a bundle of wool but unlike a bundle of wool if it's not quite in the right orientation it will just collapse and become non-functional.  One thing you have to do when you mutate, when you make a mess of enzymes a bit if you don't delete the activity the proteins become what is appearing when you put milk into your cappuccino.  The froth on top is a denatured enzyme that doesn't function any more.  We want to avoid that.  There are some tricks that we don't quite understand but it can affect the structure of the enzymes so that you avoid losses from your library.  Some clones just denature.  They just disappear and they're not selectable any more.  There are some tricks that you keep the structure constant and you start with something that is resistant to temperature.  That is then enough degrees of freedom to have enough function.

Chris - Do you think you might be able to invent an enzyme to stop punts sinking?  I think we might be taking on water here!

Florian - We might be able to make and enzyme to hydrolyse compounds that are toxic in the Cam at some stage or maybe an enzyme to help us to -

Chris - Bail out?

37:26 - Trinity College

The history of Trinity and the Wren Library

Trinity College
with Sarah Castor-Perry

The main landmark of Trinity on the river is the Wren library, designed by Sir Christopher Wren, who also designed St Paul's Cathedral in London. It holds some original works of Isaac Newton and Shakespeare and the books are all kept up on the first floor so if the river ever flooded, they wouldn't be damaged as thet're pretty irreplaceable! Trinity is the richest college at either Cambridge or Oxford. Trinity collegeIt was set up by Henry VIII in 1546 and he gave it a lot of land, property and money gained from the dissolution of the monasteries. In fact, some of the Cambridge colleges that were originally monasteries were broken up and given to Trinity as land. It used to be said that you could walk from Cambridge to Oxford on land owned by Trinity, but although they are the richest college with assets of over £700 million, this is not possible any more.

38:56 - Earth, the Universe and Everything

Astronomer Royal Professor Lord Martin Rees tells us about Earth, the Universe and Everything - from the Big Bang to the ultimate fate of the universe...

Earth, the Universe and Everything
with Professor Martin Rees, Trinity College

Chris - Another guest on our punt is Professor Martin Rees.  Martin is president of the Royal Society.  He is also the Master of Trinity College.  He's the Astronomer Royal and he's come to talk to us about life, the universe and everything.  Martin, thank you very much for coming to talk to us.

Martin - Great to be here on this sunny day.

The Andromeda GalaxyChris - Let's put some numbers on things, first of all. How old is the universe?

Martin - The universe is nearly 14 billion, 14 thousand million years old.  We know that number with a precision of about 5 per cent I would guess.  The Earth itself is about four and a half billion years old.  The first life started not much after that.  When we think about the origin of the sun and the planets we have to realise that when they formed already the universe had been expanding for about nine billion years.

Chris - 5% is pretty accurate. How do you know the universe is that old?

Martin - We know the universe is expanding.  If we know how fast an object is moving away from us and how far away it is then we can work out, roughly speaking, how long it has taken to get to that distance assuming everything started close back together.  Then you have to make corrections because the present speed is not the average speed depending on whether the universe is accelerating or decelerating.  That argument and some others has given us this picture of how long it was.  It's everything squeezed together in a very hot, dense state which we call the aftermath of the Big Bang.

Chris - How long did that go on for?  The big bang obviously occurred in a fraction of a second but then things have been evolving since.

Martin - Well, the first microsecond is still shrouded in mystery because the conditions then were rather extreme.  From then onwards we do have a fairly good general picture of how the universe evolved.  After one second it would have been at a temperature of ten billion degrees.  Soon after that hydrogen or helium atoms or nuclei of the atoms formed.  After half a million years the radiation left over from the early universe cooled to a temperature of about three thousand degrees.  That's important because that's a low enough temperature, lower than the surface of a star, where the atoms become neutral and they can start clustering together.  After about half a million years the atoms are clustering together to make the first galaxies and the first stars.

Chris - Do we know what the anatomy of those first galaxies was?  Were they similar to what we see today or were they very different?

NGC 6744Martin - We don't know quite when the first stars and galaxies formed.  We know that after the first half million years the universe because literally dark because the primordial light diluted and shifted it into red.  The universe became literally dark until the first stars formed and lit it up again.  We do believe that the first star to form not in isolation but in what I would call sub-galaxies: objects which are maybe about a million times as big as a star.  These sub-galaxies then agglomerated and merged together until systems the scale of present-day galaxies built up.

Chris - What keeps galaxies together?  Why don't they just spread out and all the matter and the material just get dispersed through space evenly?

Martin - Well, the galaxies are held together by gravity.  But the gravity of the stars and gas that we see is not enough to stop their disruption.  We know how fast they're moving and therefore how much kinetic energy has to be counterbalanced by gravity.  The important conclusion we draw from this is that galaxies must consist of not just gas and stars but also of some other ingredient, that we call a dark matter.  This material is of some uncertain nature.  It's probably some kind of particle made in the Big Bang along with the atoms and the radiation which is rather like heavy neutral atoms as it were.   They don't emit or absorb light but they feel gravity and the cluster together in a sort of swarm.  We believe that every galaxy contains not just is and gas but also a swarm of dark matter whose total mass is probably five times as big as the mass of all the stars and galaxies we see.

Chris - If they were produced in the Big Bang and they like to cluster together how did they get separated in the first place only then to come back together again at the hearts of the galaxies we have today?

Hubble_deep_field_imageMartin - The early universe was very smooth, almost uniform.  If it had been completely uniform then it would now, after 40 billion years, be just a cold, very dilute hydrogen: no galaxies, no stars and no people.  The early universe wasn't completely smooth.  It had small fluctuations: some regions denser than others, some expanding slower than others.  During the expansion the density contrasts grow under the action of gravity.  That's because if a region is slightly denser than average gravity exerts a bigger pull and slows it down more.  The density contrast grows.  Starting from very tiny non-uniformities one part in a thousand or thereabouts on can end up in the theoretical simulations of galaxy formation with structures forming at a late stage in the universe.  We believe that's what happened.  There were these fluctuations, one part in a thousand from place to place.  As the universe expanded the density contrast grew and the dense regions eventually separated out to make the first galaxies.

Chris - Dark matter which is intensively gravitationally positive and pulls things towards itself explains one aspect of what you've been saying.  One other thing that you mentioned is that the universe is expanding.  If you've got everything pulling together what's driving the opposite?  What's pushing everything apart to make it expand?

Martin - Even now if we look at the expansion of the universe it seems that it is speeding up, not slowing down.  This is rather surprising because you would expect that the gravitational pull that everything exerts on everything else would cause the expansion to slow down.  But it does seem that there is in the universe now, to everyone's surprise, an extra force which is unimportant on the scale of everyday life; unimportant in the solar system, even in the galaxy.  On the scale of the entire universe it exerts a push which overwhelms the pull of gravity and causes the expansion to be accelerating.  This tells us the long-range forecast for the universe is to become ever colder, ever emptier, ever more dilute.  We suspect also, although we don't know this, that in the early stage of the universe there was a repulsive force rather like the one operating now but much, much stronger.  That gave the universe its initial impetus, as it were.

Remnants of Kepler's SupernovaChris - Looking at the shorter range, closer to home, in our own neighbourhood - this galaxy, the Milky Way - does that mean the space between us and our next near neighbours is getting bigger to?

Martin - No, there's what we call a local group of galaxies.  There's us plus Andromeda plus a few smaller galaxies which is a system held together by its own gravity.  That's not participating in the expansion of the universe.  If we imagine what the universe would be like 50 billion years from now then it would look very empty indeed and almost everything that we now see with our telescopes will have disappeared.  What will be left will be just the remnants of our galaxy, Andromeda and a few others which by then will have merged into an amorphous galaxy consisting of dark matter and stars which will then mainly have died except the very faint slow-burning ones.

46:27 - St John's College

St John's College and the Bridge of Sighs

St John's College
with Sarah Castor-Perry

The most famous part of St John's is known as the Bridge of Sighs - one of the college's two bridges over the Cam (it's the only college to have two bridges). It is modelled on the original Bridge of Sighs in Venice, but as anyone who has seen the Venetian original will realise, it doesn't look much like it, except that it has tall sides and a roof.St John Another interesting fact is that St John's College fellows are the only people apart from the Royal Family who are legally allowed to eat swans. There are swan traps in the walls of the college by the river, but these are no longer used.

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