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A punt on the Cam

A punt on the Cam

This week on The Science Show Cambridge virologist Chris Smith takes us punting along the Cam
River. As he weaves around the old stone colleges, scientists jump on and off the punt, discussing
their work as they go. A local guide describes the intriguing history of Cambridge, its colleges
and the beautiful bridges across the river. The punt traverses The Backs, a one-mile stretch of
river that supports some of finest examples of architecture in England.

Transcript

Chris Smith: This is the city that was home to Isaac Newton and his famous apple tree, Henry
Cavendish, the man who discovered hydrogen and also worked out how to weigh the Earth, the Kiwi
Ernest Rutherford who discovered the structure of atoms, and just around the corner is the Eagle
Pub where James Watson and Francis Crick announced in 1953 that they'd uncovered the secret of
life, which was the structure of DNA.

I am of course in Cambridge, and one of the most significant features of the city is the river Cam
which runs right through the middle of some of the most historic and important of Cambridge
University's colleges. Unusually for Britain, the weather is absolutely fantastic, so I'm going to
take a cruise down the river and meet some of the scientists that are helping to make Cambridge
great today. So let's meet the person who is going to be our guide. This is Sarah Castor-Perry. So,
are you from Cambridge?

Sarah Castor-Perry: Yes, I was a student here.

Chris Smith: So what are you going to be showing us?

Sarah Castor-Perry: I'm going to be taking you down what is known as The Backs which is the bit of
the river that goes past all the old colleges, such as Queens and Clare and Kings, all the big ones
that the tourists come to see.

Chris Smith: And on our journey down the river we'll be meeting some of the fellows. In fact we'll
be getting them as passengers in our boat right down the river. Fellows are dons of Cambridge
colleges, so they do research and they also do teaching, so we'll be asking them about what they're
working on. So Sarah, where's the craft that we're going to be going in?

Sarah Castor-Perry: The boat's here, the punt is a flat-bottomed boat made of wood, and it has
traditionally been used since the 19th century for carrying cargo and fishing and things, but
actually it's quite common now to see it in Oxford and Cambridge for pleasure trips.

Chris Smith: You mean we're getting in that?!

Sarah Castor-Perry: Yes. They do say it is impossible to sink a punt but I do have friends who have
sunk them before, but I'll try not to sink you.

Chris Smith: You're not filling me with encouragement. Where's the engine?

Sarah Castor-Perry: It's punted by a pole. You push the pole in and lever yourself along the bottom
through the water.

Chris Smith: And where do you go and pump from?

Sarah Castor-Perry: I stand on the bit at the very end which is a big flat bit known as the till.

Chris Smith: So you want me to get some of Cambridge's finest minds into that?

Sarah Castor-Perry: I promise I won't sink it.

Chris Smith: Okay, right, let's take it away.

Sarah Castor-Perry: Let's get in. If you get in first and then I'll go along and I'll punt us off.

Chris Smith: I think probably the best way I can describe this is a bit like an oversized canoe
that someone has forgotten to put the top on. This is about 20 feet long, it's about wide enough
for two people to sit side by side at various points along the length, and there are cushions made
from canvas that sit on the bottom of the punt which we then sit on, and then at the back is a
raised flat deck area which I presume is where Sarah is going to stand to push us along. Where are
we going first?

Sarah Castor-Perry: We're going to be going to Queens College first.

Chris Smith: It's pretty busy on the river, Sarah.

Sarah Castor-Perry: Yes, it usually is in summer and also on weekends it's particularly busy, and
The Backs is worse because this is where a lot of the inexperienced punters tend to go. So when
it's busy, like it is at the moment, you get a lot of crashing punts and lost poles.

Chris Smith: Where are we now?

Sarah Castor-Perry: We're just about to go under Mathematical Bridge which spans the river between
the new and old bits of Queens. It's the only wooden bridge on the Cam, as you can see, and it's
held together by metal bolts between the bits of wood. There's a bit of a legend about this bridge
which quite a lot of the punters tend to tell the tourists which is that it was originally built by
Newton without any bolts at all and that the bits of wood, because he designed it so perfectly,
just held together without any bolts, and the students took it apart to see how that worked but
then couldn't put it back together again. The engineering department couldn't do it, so they had to
rebuild it with bolts in it. But this, sadly, is not true.

Chris Smith: Why not?

Sarah Castor-Perry: Because actually the bridge was first built 22 years after Newton was already
dead. It was rebuilt twice in Queens' history but it's always had metal bolts in it.

Chris Smith: Anything else special about Queens?

Sarah Castor-Perry: It's one of only two colleges in Cambridge which has buildings on either side
of the river on its main site, the other one is St Johns, and it also has the oldest building on
the river, which was built in the 15th century.

Chris Smith: And what's its history?

Sarah Castor-Perry: It was founded in 1448 by Margaret of Anjou who was married to King Henry VI,
and then it was re-founded in 1456 by the wife of King Edward IV, hence its name, Queens.

Chris Smith: So it's all logical. Was it always a university college? Was there always education
going on there then?

Sarah Castor-Perry: Yes, it was founded originally as an educational college as opposed to quite a
lot of the other colleges which were originally monasteries, Magdalene and Sidney Sussex both
started off as monasteries that were then converted for education.

Chris Smith: We'd better pick up our first passenger here from Queens, and that is from Plant
Sciences, Beverley Glover. Welcome Beverley.

Beverley Glover: Hi Chris.

Chris Smith: I'm sorry, 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 could do.

Beverley Glover: It's all right, we're quite used to it in Cambridge!

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

Beverley Glover: Most of our work at the moment is about the surface of the flower, particularly
the surface of the petals, and how different structures on those surfaces affect the way the flower
interacts with the animals that collect its pollen and pollinate it.

Chris Smith: How do flowers actually work?

Beverley Glover: 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, the good thing to
eat, which is usually nectar, and in doing so picks up a bit of the plant's pollen and transfers it
then to another flower and that way the plants gets fertilised and make seed.

Chris Smith: But what about in terms of how the flower mechanically works? If you zoom in with a
microscope and look at it in more detail, what's actually there?

Beverley Glover: Different flowers have different surface structures depending on what they're
trying to attract. Different animals have different preferences. One thing we've been looking at is
whether some flowers have cell structures that give grip to animals so that if they're trying to
land perhaps 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 the nanometre scale which affect
the way light is reflected and refracted and can give you iridescence on the flower.

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

Beverley Glover: Yes, exactly. So 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 would to us and makes it very
attractive to them.

Chris Smith: Why do you think insects want to see the UV? Where do they get that trait from?

Beverley Glover: 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. So 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 Smith: Is it anything to do with the fact that on a cloudy day UV can still come through and
other light wavelengths might not?

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

Chris Smith: Why would they need colour vision if there was no flower around for them to pollinate?

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

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

Beverley Glover: 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 into the flower to make it
look brighter, so we can see that effect. They may also make the flower warmer by trapping heat. So
when they trap light, they trap energy, and so they make the flower slightly warmer, and that, to
some pollinators in some environments, may be the most significant factor; a warmer flower means
that you don't have to spend as much energy warming yourself up.

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

Beverley Glover: 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. The difference these cells can make to how warm the flower is isn't very great for a
flower on a sunny day in a normal habitat. But 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 Smith: Why does it make a difference? Why does an insect want to drink warm nectar?

Beverley Glover: Because it doesn't have to spend any energy warming it up itself. Bees 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 Smith: 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 Glover: Yes, so we have a mutant line of snap dragon, Antirrhinum majus, and also a mutant
line of petunia that don't make these cells. And although they're perfectly fit and grow perfectly
well in the greenhouse, if we plant them out in the field we find that 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 then, in the plants that
have 'deliberately' lost them, the flowers that never have them, what has happened to those genes
and where they've gone and why they're not working any more.

Chris Smith: So does this mean that if gave plants more genes or expressed them more so they made
more of these cells you could make them more fertile, more fit and you'd get better yields off
them?

Beverley Glover: 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 that are attracted to it don't need them, either for grip or
for the vision. But the tomato itself hasn't lost them, so one thing we're interested in exploring
at the moment is if we knock those genes out of the tomato can we make it actually more attractive
to pollinators and set more fruit.

Chris Smith: 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 Glover: You know, it's funny, my husband makes that joke all the time as well!

Chris Smith: Beverley Glover from Plants Sciences at Cambridge University talking about conical
cells and how they can warm up plants and make the petals much more attractive to insects and
therefore they might want to pollinate them.

Right, where are we now, Sarah? Where have we ditched Beverley?

Sarah Castor-Perry: This is Kings College, and on the right you can see the huge Kings chapel,
which is one of the most famous landmarks in Cambridge. It was started in 1441 by Henry VI, but
then in 1455 the War of the Roses started, which basically took up all the king's funds because he
had to go and pay for the army, so it actually wasn't finished until Henry VIII came along and
finished it in 1544. And you can actually see on the chapel that one side was finished much earlier
than the other because about ten feet up off the ground on one of the sides you can see the colour
of the stone changes because it was actually completed several years after it was started.

Chris Smith: Do you think they did it on the cheap?

Sarah Castor-Perry: Yes probably, after the War of the Roses. That must have left them pretty
crippled financially.

Chris Smith: So what else is Kings famous for?

Sarah Castor-Perry: It's famous for it being originally set up for just boys from Eton school, so
that's quite an exclusive little club, and they only started letting in non-Eton boys in 1865.

Chris Smith: And what about, dare I say, in Cambridge, women?

Sarah Castor-Perry: They were let in considerably later, in the 20th century, but they're not quite
as old fashioned as Magdalene who didn't let then in until the 1970s.

Chris Smith: Thank you very much, Sarah.

Right, here's our next passenger waiting on the banks of the Cam to join us in our punt, and he's
going to tell us about some novel and clever ideas in how we sequester carbon and therefore offset
our carbon footprint, and that's Professor Herbert Huppert. Herbert, welcome to our punt, welcome
aboard.

Herbert Huppert: Thank you very much. It's a little rocky, but it's fun sitting here.

Chris Smith: 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're pumping out
into the atmosphere?

Herbert Huppert: You know, we're pumping out something like 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 in Australia
and the great heat in 2003 that killed so many people in Europe. So 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 Smith: Some people say, though, that the reason that you see a rise in CO2 with a rise in
temperature is that water doesn't absorb as much CO2 when it's warmer. So if you warm the world up
then CO2 comes out and goes in the air.

Herbert Huppert: What is clear is that there is a good chance that because of the increased carbon
dioxide that we're putting into the atmosphere, the temperature is rising because of that.

Chris Smith: What sort of strategies are there to try to get the carbon dioxide out of the
atmosphere and also to prevent us putting so much there in the first place?

Herbert Huppert: 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 two 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, but the one that is most likely to work is
to store the carbon dioxide for at least 10,000 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...not
as much storage space there available to us, but that's another possibility.

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

Herbert Huppert: The point is that normal carbon dioxide as we know it is a gas, and a gas takes up
a relatively large amount of space compared to a liquid, something like a 1,000 times more. We can
compress the gas into a liquid by taking it down to a minimum of 800 metres, but better somewhere
between one kilometre and two kilometres. You have to pump it down one kilometre, let's say,
normally, where it becomes supercritical gas, as it's called. It's like a liquid, it has a density
close to water, about three-quarters that of water, and then it flows out into these pores in the
rock, really just like oil has been formed in pores.

Chris Smith: How do you keep it there?

Herbert Huppert: 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 really from a theoretical point of view, is to somehow play some
game with the density so that the density of the liquid-like carbon dioxide is larger 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 gets somehow or other less dense and then it would
come to the surface by itself.

Chris Smith: There are some 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, so it's sequestered as a rock.

Herbert Huppert: The question is how much energy is needed to do that, energy in the sense 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 that 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. So we need something like 100,000
such field stations, and we're a long way from getting there.

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

Herbert Huppert: 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, and at the moment no thought
whatsoever has been given to where you might sequester their carbon dioxide.

Chris Smith: You mentioned parts of the former Soviet Union. Of course 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 . So I suppose there's that to take into account
as well.

Herbert Huppert: Yes, 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. But 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 Smith: Are you worried?

Herbert Huppert: 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.

Chris Smith: That's what I call keeping cool, even in the face of global warming. That's Professor
Herbert Huppert who's looking for places to put carbon dioxide where it can't cause trouble.

We are of course punting our way along the river Cam in Cambridge and passing through the grounds
of some of the most important colleges at the university where we're picking up passengers in the
form of research fellows. Sarah Castor-Perry is doing all the hard work; she's punting us along
with a big, long pole. Sarah, where have we got to?

Sarah Castor-Perry: This is Clare College which is actually the second oldest college in Cambridge
after Peterhouse, although having said that you wouldn't think so looking from The Backs because
the buildings along the river were actually built in the 17th and 18th century, so a lot of people
think it's actually younger but it's not.

Chris Smith: And what's Clare famous for?

Sarah Castor-Perry: One of the things Clare College is most famous for is Clare Bridge which is the
oldest surviving bridge over the Cam, and the famous thing about it is that it's got 14 stone balls
along the top and one of them has a chunk missing.

Chris Smith: So it's the Hitler of Cambridge bridges, you might say.

Sarah Castor-Perry: I suppose so, although it does have 13 complete balls and one slightly
misshapen ball because it's got a slice missing, it looks a bit like a cheese, and one of the
stories about this is that when the stone mason built the bridge, Clare didn't pay him as much
money as he wanted, so to spite them he cut out a chunk of one of the balls on the bridge and took
it away to even up his payment.

Chris Smith: He could have done something more dramatic, like actually take away half the bridge,
which would actually have made a difference.

Sarah Castor-Perry: Yes, that would have made more sense, and actually the story is probably not
true because when the balls erode...they're held to the bridge by metal rods, and when they get old
they start to get a bit loose, and the way to repair them is to cut out a chunk at the bottom and
then twist them round and put them up on their other side and then fill in the chunk that you've
cut out with another piece of stone which presumably over time somehow fell out and is somewhere in
the river and they haven't replaced it...which comes up with a great story but I think that's
probably more what happened.

Chris Smith: Anything else we should know about Clare?

Sarah Castor-Perry: One of their most illustrious fellows is David Attenborough, the great
naturalist, so everyone is very proud of that.

Chris Smith: Well, quite a hard act to follow but I think we may have a close contender with our
next passenger, and that is, from Clare College and the Department of Psychiatry, Paul Fletcher.

Welcome to our punt. I'm sorry that this is the best we could do. It's a low-budget program.

Paul Fletcher: This is absolutely beautiful, don't worry.

Chris Smith: It's a nice day for it, actually, isn't it?

Paul Fletcher: It's glorious, it's absolutely perfect.

Chris Smith: What is it you work on?

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

Chris Smith: What do they actually mean?

Paul Fletcher: They both relate to a very changed experience of the world. A hallucination is when
you hear something or see something that isn't really there. A delusion is when you believe
something that is really quite extraordinary and probably untrue. For example, a hallucination,
somebody might hear somebody talking to them, criticising them, casting aspersions on them in
various ways. A delusion, they might come to believe that their neighbours are trying to poison
them or control their actions.

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

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

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

Paul Fletcher: 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. But we know that there are clues that this might be one of the
prime suspects. The real thing that we don't know is how that something as basic and low-level as
that can translate into something as complex and human and social as a belief that somebody is
trying to harm you.

Chris Smith: It's interesting because schizophrenia is quite genetic, we know it runs in families,
but it also tends to come on much later in life, even though presumably the genes that cause it are
active from the time that you're conceived, effectively. You don't get the disease until your
mid-20s, in some cases a bit later, in some cases in your 70s. What do you think is going on in the
brain to suddenly make this come out when we're that bit older?

Paul Fletcher: 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. My own view is that the sorts of symptoms that people
experience and suffer from in schizophrenia are much more the preoccupations of the adult and of
the adult brain, and that in children it manifests in much more simplistic ways; motor
abnormalities, speech abnormalities.

Chris Smith: 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 Fletcher: Up until the 70s, people gave an unequivocal 'no' to that, and then in the mid-70s
somebody called Eve Johnstone in Northwick Park produced a ground-breaking paper which essentially
showed that the ventricles, which are the fluid-filled spaces in the brain, tend to be larger in
people with schizophrenia. This suggests that there's been some degree of shrinkage of the brain.
Now most psychiatrists would accept that the brain is different in structure, and there's
increasing evidence that it is different in the way it functions.

Chris Smith: 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. And we know that we continue to make new brain
cells throughout life in certain parts of the brain. So do you think this is some kind of thing
that you grow into? You slowly accumulate enough cells as your brain ages and produce these new
neurons that they make new pathways that perhaps connect up the wrong bits of the brain and
disclose schizophrenia?

Paul Fletcher: The very name 'schizophrenia' itself means a splitting of the mind, and while many
laypeople 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, which allows us 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 Smith: 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 there's something real.

Paul Fletcher: Yes, work that has been done in the past suggests that an auditory hallucination,
which is very often a voice saying very intimate things about the sufferer, is probably
self-generated, it's their internal speech. There's good evidence that...normally when you 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, whereas 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, and 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. Again, 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 Smith: Finally, are we closer to helping people to lead some kind of normal life once they're
diagnosed with something like schizophrenia?

Paul Fletcher: 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. Observations of that is suggesting that 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.

Chris Smith: Thank you very much to Paul Fletcher who is from the Department of Psychiatry and also
a fellow of Clare College, which as you told us earlier, Sarah, is the college of bridges and balls
and David Attenborough, which is obviously a lot to be proud of. Where are we now?

Sarah Castor-Perry: This on the right is Trinity Hall, and this was founded in 1350 and it was
originally founded to train lawyers to replace all the ones that died in the Black Death of a few
years earlier.

Chris Smith: I wish they hadn't built it.

Sarah Castor-Perry: Yes, I don't know why they thought more lawyers were needed in the world,
but...

Chris Smith: Well, in one respect they're absolutely right, but now they've taken over the world,
haven't they.

Sarah Castor-Perry: Yes, they have a bit. It does still have a very strong law faculty within the
college but it's not as strong as it used to be.

Chris Smith: So do you have to be a sort of law geek to get in there then?

Sarah Castor-Perry: Yes, I suppose so, but I think you have to be a bit of a geek to get into most
Cambridge colleges really.

Chris Smith: This is someone who went to Cambridge until recently. Which college were you at then?

Sarah Castor-Perry: I was at Sidney Sussex.

Chris Smith: A bit of a poor place really, a bit of a poor excuse, not on the river.

Sarah Castor-Perry: No, we don't have a river but we do have our own punt, so we're trying to get
in there.

Chris Smith: It's not very useful having a punt if it's not on the river, is it?

Sarah Castor-Perry: No, we've snuck it into Magdalene to moor it there.

Chris Smith: Okay, so you don't have to punt down the road, which sounds really rather difficult.

Sarah Castor-Perry: Yes, it would be quite difficult. I know someone who punted a trolley in one of
the parks in Cambridge using a punt pole and a trolley. It was quite fun and quite difficult.

Chris Smith: Sounds like something you might see on Jackass.

Anyway, 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.

Florian Hollfelder: Yes, I work on enzymes, and we try to take an unorthodox approach to
understanding enzymes. Normally scientists like to be very controlled but we do it differently; we
make a mess first and then try to find, in what we call a library, single molecules out of large
collections of 108 or 109 molecules and find the right one. So it's a bit like trying to find the
needle in the haystack and hopefully we are successful in doing that

Chris Smith: But what's the actual point of what you're doing?

Florian Hollfelder: 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, very complicated and difficult to do in the lab. But 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 Smith: That's how fast it makes a reaction go compared with if you didn't have the enzyme
there?

Florian Hollfelder: That's right, yes, 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
then suddenly proteins get degraded very, 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 further
into the unknown, and that's why we use this 'library' approach where we give up on thinking for a
moment and then fish out something that turns out to be better than all the other molecules, and
this is actually how nature found these molecules.

Chris Smith: So 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 looking to find out how these chemical reactions
occur using enzymes in the first place and how we can find better ones.

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

Chris Smith: Do you mean, in other words, you're making different versions of an enzyme...when you
say 'make a mess', you just make lots of different forms of it and then you find the one which
works best and then ask why?

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

Chris Smith: 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 Hollfelder: Correct, this is exactly what we do, yes.

Chris Smith: So what sorts of reactions are you looking at?

Florian Hollfelder: 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 if one enzyme does not have only one partner but
several partners with whom it can engage, several molecules that can turn over, and often these are
different chemistries that it can do. That's why these promiscuous enzymes are, for us, the
starting point for evolution. You're more likely to recover one clone with a new activity if you
already had a little bit of it originally.

Chris Smith: What sorts of things, apart from washing powders, are you looking at then?

Florian Hollfelder: For example, we are looking at phosphatases and some of the pesticides that
have been put in nature in the 50s 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 Smith: Have you got any enzymes that you've identified that do that job well now then?

Florian Hollfelder: 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 at industrial application but we
can show we can at least, because the tricks we've developed in the technology were very important.
What we've learned in the process of that is that you have to manage these enzymes in some way that
you try to keep them generalists for a long time. In principle you want to start off with a
jack-of-all-trades that can do everything just not very well but it can do everything just a bit.
And then you enhance that background activity to get better. If you don't have anything to start
off with, you can't select. You do these complicated transformations and make your DNA libraries
but in the end you find nothing. And so after years of frustration we finally found that 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 Smith: You say you make a mess and then 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 go and have a look at it and try and find out why?

Florian Hollfelder: Yes, so we then crystallise it, we wait for it to form well-defined materials,
crystals that you can diffract. These are techniques that were developed in Cambridge in the 50s,
and now it's fairly standard that even an amateur like me, together with a good collaborator, can
start making crystals. That then gives us insight in the inner workings of the enzymes, so 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 an enzyme for a specific application,
we now know where to start.

Chris Smith: 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 one off the shelf that you've made earlier, or
you'll know exactly how to tweak something to add an activity - a certain chemical reaction or
ability to do something well - to an enzyme that already exists.

Florian Hollfelder: Yes, that's right. And the other thing that I think we haven't cracked quite
yet is how nature can do it so efficiently, because very often we find that 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, is that you don't delete the activity, that
the proteins become what is appearing when you put milk into your cappuccino, the froth on top,
that's actually denatured enzyme but it does not function any more. We want to avoid that. There
are some tricks that we don't quite understand that it can affect the structure of the enzymes so
that you avoid loss in your library. Some clones just denature, they disappear, and they're not
selectable any more. There are some tricks now that you keep the structure quite constant, that you
start with something that is resistant to temperature, and that has then enough degrees of freedom
to find the new function.

Chris Smith: Do you think you might be able to invent an enzyme to stop punts sinking, because I
think we might be taking on water here!

Florian Hollfelder: I could probably make an enzyme that helps us to hydrolyse compounds that are
toxic in the Cam at some stage or maybe an enzyme to help us to...

Chris Smith: Bail out?

Florian Hollfelder: Maybe, maybe.

Chris Smith: Thank you very much Florian Hollfelder.

Florian Hollfelder: Great, thank you very much.

Chris Smith: Great to have you aboard. Mind your step, don't fall in.

We're almost at the end of our trip along the river Cam courtesy of the person who's punting us,
and that's Sarah Castor-Perry, and this place, Sarah, is an incredibly impressive building. Where
have we got to?

Sarah Castor-Perry: Well, what you can see on the right is the Wren Library which is part of
Trinity College, and this was designed by Sir Christopher Wren who designed St Paul's Cathedral in
London. This holds some of the most famous work by Isaac Newton who was a fellow of Trinity. As you
can see, the library is on the top floor and the second floor, so if the river ever flooded
(because it's right next to the river) the books wouldn't get all soggy.

Chris Smith: Which is kind of important considering they must be irreplaceable. They are, aren't
they?

Sarah Castor-Perry: Yes, definitely, quite a lot of the books are over 200 years old, so definitely
irreplaceable.

Chris Smith: What else is Trinity famous for?

Sarah Castor-Perry: It's the richest college in either Oxford or Cambridge. It was set up by Henry
VIII in 1546 and he gave it a lot of land and property and money from the dissolution of the
monasteries, and in fact some of the colleges in Cambridge that used to be monasteries were broken
up and given to Trinity as land and it used to be said that you could walk all the way from
Cambridge to Oxford on land owned by Trinity. Although they are the richest college, with assets of
over 700 million pounds, walking from Cambridge to Oxford is not actually possible on Trinity land.

Chris Smith: But then, why would you want to go to Oxford, for heavens sake!

Anyway, here's our final passenger coming down the bank to meet us, that's Professor Martin Rees.
Martin is president of the Royal Society. He is also the Master of Trinity College and the
Astronomer Royal, so that means he's going to talk to us about life, the universe and everything.
Martin, great to have you with us.

Martin Rees: Great to be here on this sunny day.

Chris Smith: Let's put some numbers on things, first of all. Actually how old is the universe?

Martin Rees: The universe is nearly 14 billion, 14,000 million years old. We know that number with
a precision of about 5%, I would guess. The Earth itself is about 4.5 billion years old, and the
first life started not much after that. So 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 Smith: Five-percent, that's pretty accurate. How do you know the universe is that old?

Martin Rees: 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. But 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 have given us this picture of how long
it was since everything squeezed together in a very hot, dense state which we call the aftermath of
the Big Bang.

Chris Smith: 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 Rees: 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 3,000 degrees, and
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 start clustering together to make the first galaxies and the first stars.

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

Martin Rees: We don't know quite when the first stars and galaxies formed. We know that after the
first half-million years the universe became literally dark because the primordial heat and light
diluted and shifted into infrared. The universe became literally dark until the first stars formed
and lit it up again. But we do believe that the first stars 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, and these
sub-galaxies then agglomerated and merged together until systems the scale of present-day galaxies
built up.

Chris Smith: 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 Rees: 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 because 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, what we call dark matter. This material is of some uncertain nature. It's probably some
kind of particles made in the Big Bang along with the atoms and the radiation which is rather like
heavy neutral atoms as it were, and they don't emit or absorb light but they feel gravity and they
cluster together in a sort of swarm. We believe that every galaxy contains not just stars 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 gas we see.

Chris Smith: 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?

Martin Rees: 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. But the early universe wasn't completely smooth, it had small fluctuations,
some regions slightly denser than others, some expanding slightly 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, so density
contrast grows. So, starting from very tiny non-uniformities (one part in 100,000 or thereabouts)
one 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, that there were these fluctuations, one
part in 100,000, from place to place, and as the universe expanded, the density contrast grew, and
the dense regions eventually separated out to make the first galaxies.

Chris Smith: 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, so if you've got everything pulling together, what's driving the
opposite effect, what's pushing everything apart to make it expand?

Martin Rees: 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, but 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. And that gave the universe its initial impetus, as it were.

Chris Smith: Looking at the shorter range, closer to home, in our own cosmic neighbourhood, this
galaxy, the Milky Way, does that mean the space between us and our next near-neighbours is getting
bigger too?

Martin Rees: No, there's what we call a local group of galaxies, which is 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, say, 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 a large amorphous galaxy consisting
of dark matter and stars which will then mainly have died except the very faint slow-burning ones.

Chris Smith: So it's fair to say that the universe doesn't have a bright future in front of it, but
thank you very much all the same to someone who certainly does and that's Professor Sir Martin
Rees.

That's it for our scientific tour of Cambridge from the river Cam. I have to say a very big thank
you to the researchers who've joined us on board our punt today, that's Beverley Glover, Herbert
Huppert, Paul Fletcher, Florian Hollfelder and Martin Rees, and of course Sarah Castor-Perry who
kept us afloat throughout. All we need to do is get this punt back by five o'clock, Sarah, or we're
going to lose our deposit.

Eruption of Sumatra's Mt Toba

Eruption of Sumatra's Mt Toba

Martin Williams found volcanic ash in India. It came from Mt Toba in Sumatra 73,000 years ago. The
explosion of Mt Toba was the biggest bang in 2 million years. For comparison, Krakatoa ejected
about 18 cubic kilometres of ash and rock. It's thought Toba ejected 3,000 cubic kilometres of ash
and rock. The eruption of Toba changed world climate. Temperatures in Greenland dropped 16 degrees.

Around 100,000 to 50,000 years ago, world population plummeted to just a few thousand individuals
prior to recolonisation out of Africa. Martin Williams speculates the eruption forced people to
develop social networks and reciprocal relationships and this assisted in the movement back out of
Africa.

Transcript

Robyn Williams: Professor Martin Williams from Cambridge but who is now an emeritus professor at
the University of Adelaide, has been in pursuit of one of the biggest bangs in history which made
us who we are. Martin, do tell.

Martin Williams: Quite by accident, in February 1980, I was in north central India and we'd logged
70 kilometres length of cliff sections in the Son Valley, beautiful valley, Siddhartha country, and
we spotted something unusual halfway up this 30-metre cliff. I turned to Keith and said, 'Were this
the Ethiopian highlands I'd call that volcanic ash.' Since no volcanic ash has ever been recorded
in geologically recent times in India, we sampled it every centimetre.

So we fingerprinted it. Every eruption, as you know, has its own individualistic signal, its own
geochemical fingerprint, and it turned out to come from northern Sumatra, 73,000 years ago, and
Sumatra or Toba, is now just a big, beautiful lake. It ejected something like 3,000 cubic
kilometres of rock equivalent in the form of ash. Compare that to Krakatoa which is about 14 to 18
(cubic kilometres of rock), so we're talking about orders of magnitude difference. Krakatoa of
course killed 42,000 people.

So what was the impact of this huge eruption, the biggest explosive eruption in at least the last
two million years, probably a great deal longer? Once I'd put it on record, the lads and lasses of
the Indian geological survey found it everywhere, it was all over India. It was in the Bay of
Bengal, it turned up in the Arabian Sea, it turned up 12 degrees south of the equator in the Indian
Ocean. Then it turned up in the East China Sea and in Greenland. In the sulphur spike in Greenland
associated with it you have a 16-degree drop in temperature, which is quite dramatic...

Robyn Williams: It's gigantic, isn't it!

Martin Williams: Yes. And a decade-and-a-half ago a number of very cluey geneticists were looking
at the mitochondrial DNA inherited through the female in human populations, and they speculated
that somewhere between 100,000 and 50,000 years ago the world population plummeted down to a few
thousand males and females.

Robyn Williams: It was about 20,000 they said, roughly.

Martin Williams: It varies. Some estimates say 2,000, some say 5,000, some say 10,000. So 20,000 is
not a lot. And then re-colonisation out of Africa. Since that time there's been a raging...no,
academics don't rage, they're too polite for that, but there's been some fairly brutal debate. One
school says there was no impact whatsoever because when you look at the artefacts in southern India
above and beneath the ash they're the same, they're middle Palaeolithic, middle stone age,
therefore no impact.

So I thought I'd take a different approach and did a transect across central India, about 500
kilometres, and we sampled soils beneath the ash and above and the carbonate nodules in them, and
we analysed the carbon isotopes 12 and 13. And so we had a fix on the type of vegetation that was
growing at the time, what photosynthetic pathway it followed so we could distinguish C3 from C4.
And in essence beneath the ash, right across central India, forest, and above the ash, mixed
woodland and grassland. So that's a fairly indirect form of evidence.

So then we...in a couple of marine cores, one just off north Sumatra, one in the Bay of Bengal, we
looked in fine resolution at the pollen, and the pollen shows initially dramatic cooling, quite
significant cooling, but it didn't persist. But the more interesting thing is that what you then
see is prolonged drought lasing about 1,200-1,500 years. That would have been pretty tough on human
societies of the day. They would have had to adapt. Some of our work in the west Kenya rift...we're
trying to document there the transition from middle to late Stone Age time.

Putting it in modern terms, would you give your wife a frying pan for her birthday or would you
give her a pearl necklace? Well, middle Stone Age people opted for frying pans, late Stone Age for
necklaces. And what you see in late Stone Age times is much more care being taken in selection of
the raw materials to make stone tools, you see the first evidence of objects of great beauty being
made which had no utilitarian value, on the face of it. So we found and excavated, for example, a
factory which was ostrich eggshell beads for making necklaces for the women.

And one can speculate here (and it's purely speculative) that the impact of this catastrophic
eruption and the effect it had both on the vegetation, both directly in terms of blasting the
vegetation and indirectly in terms of the effect on climate, forced people to develop social
networks, forced them to develop reciprocal relationships. And that assisted then in the movement
back out of Africa, across the deserts of Arabia and Pakistan, Afghanistan and back into India and
south Asia generally.

Robyn Williams: What a story! Some people have said that the reason that we're one race is that
having been reduced to such a small bunch of people who, if you like, were the originals of Eves
and Adams and led to all of us, means that we have less variety...well, we've got no variety, we're
one species, and it stems from that explosion, it stems from that reduction in the population. Is
that controversial? You said that there was some barnies about it, but is it..?

Martin Williams: Oh yes, a lot of people are yet to be convinced. In fact, more people are happy to
accept the impacts of small volcanic eruptions...Pinatubo, for example, June '91, global
temperatures, as you know, dropped nearly three-quarters of a degree Celsius over the next 12
months, which was equal to the net average global warming of the preceding 100 years. And that was
a fairly minor eruption. I've seen the impact at first hand of Mt St Helens near Seattle and that's
pretty dramatic, but again, very small beer compared to Krakatoa. Krakatoa is...

Robyn Williams: ...a quarter of Toba.

Martin Williams: Well, quite, yes. So Toba was quite something. And I think no one research team
will resolve this. We need a whole variety of approaches. But a number of geneticists now are
looking very carefully at the so-called bottlenecks or founder populations in tigers, in gorillas,
in macaque monkeys, and once again you're finding this curious bottleneck around about this time.

Robyn Williams: The full fascinating story is on In Conversation with Professor Martin Williams
next Thursday 11th September on ABC Radio National at 7.30pm. He's Professor Emeritus at the
University of Adelaide. Do avoid big bangs.