[Intro Music]
[Applause]
What I am going to show you are the astonishing molecular machines that create the living
fabric of your body. Now, molecules are really, really tiny, and by tiny I mean really.
They're smaller than the wave length of light. We have no way to directly observe them,
but through science we do have a fairly good idea of what's going on down at the molecular scale.
But, so what we can do is actually tell you about the molecules but we don't really have
a direct way of showing you the molecules. One way around this is to draw pictures,
and this idea is actually nothing new, scientists have always created pictures as part
of their thinking and discovery process. They draw pictures of what they are observing with their
eyes, through technology like telescopes and microscopes, and also what they are thinking
about in their minds. I've picked two well known examples because they both...
they're very well known for expressing science through art, and I start with Galileo, who used
the world's first telescope to look at the moon, and he transformed our understanding of the moon.
The perception of the 17th century was the moon was a perfect heavenly sphere, but
what Galileo saw was a rocky, barren world, which he expressed through his water colour painting.
Another scientist with very big ideas, the superstar of biology, is Charles Darwin,
with this famous entry in his note book. He begins in the top left hand corner with I think,
and then sketches out the first tree of life, which is his perception of how all the species,
all living things on Earth, are connected through evolutionary history, the origin of
species through natural selection, and divergence from an ancestral population.
Even as a scientist, I used to go to lectures by molecular biologists and find them completely
incomprehensible, with all the fancy technical language and jargon that they would use in
describing their work, until I encountered the artworks of David Goodsell, who was a
molecular biologist at the Scripps Institute. And his pictures are all, everything is accurate,
it's all to scale, and his work illuminated for me what the molecular world inside us
is like. So in the top left hand corner you've got this yellow-green area, this is a transaction
through blood. The yellow-green areas is the fluids of blood which is mostly water,
but it is also antibodies, sugars, hormones, that kind of thing, and the red region is a slice
into a red blood cell, and those red molecules are haemoglobin, they are actually red, that's
what gives blood its colour, and haemoglobin acts as a molecular sponge to soak up the
oxygen in your lungs and then carry it to other parts of the body. I was very much inspired
by this image many years ago, and I wondered whether we could use computer graphics to
represent the molecular world. What would it look like, and that's how I really began.
So, um, let's begin.
This is DNA in its classic double helix form, and it's from X-ray crystallography, so it's
an accurate model of DNA. If we unwind the double helix and unzip the two strands, you
see these things that look like teeth, those are the letters of genetic code, the 25,000
genes you've got written in your DNA. This is what they typically talk about,
the genetic code, this is what they are talking about. But I want to talk about a different aspect
of DNA science, and that is the physical nature of DNA, and it's these two strands that run
in opposite directions, for reasons I can't go into right now, but they physically run
in opposite directions, which creates a number of complications for your living cells, as
you're about to see, most particularly when DNA is being copied. And so, what I am about
to show you is an accurate representation of the actual DNA replication machine that's
occurring right now inside your body, as at least 2002 biology. So DNA is entering the
production line from the left hand side, and it hits this collection, this miniature biochemical
machines that are pulling apart the DNA strands and making an exact copy. So DNA comes in
and hits this, this blue donut shaped structure, and it's ripped apart into its two strands.
One strand can be copied directly, and it can be seen spooling off, down to the bottom there,
but things aren't so simple for the other strand, because it must be copied backwards,
so it's thrown out repeatedly in these loops and copied, one section at a time, creating
two new DNA molecules. Now, you have billions of this machine, right now, whirring away
inside you, copying your DNA with exquisite fidelity. It's an accurate representation
and it is pretty much at the correct speed for what is occurring inside you.
I've left out error correction and a bunch of other things.
[Laughter]
This was work from a number of years ago...
[Applause]
Thank you, this was work from a number of years ago, but what I show you next is updated
science, it's updated technology. So again, we begin with DNA, and it's jiggling, wiggling
there because of the surrounding super molecules, which I've stripped away so you can see something.
DNA is about 2 nanometres across, which is really quite tiny, but in each one of your cells,
each strand of DNA is about 30-40 million nanometres long, so to keep the DNA organised,
to keep, ah, regulated access to the genetic code, it's wrapped around these purple proteins,
I've labelled them purple here, it's packaged up and bundled up. This is, all of this field
of view, is a single strand of DNA. This huge package of DNA is called a chromosome, and
I'll come back to chromosomes in a minute. We're pulling out, we're zooming out, out
through a nuclear pore, which is sort of the gateway to this compartment which holds all
the DNA called the nucleus. All of this field of view is about a semester's worth of biology
and I've got seven minutes, so we're not going to be able to do that today.
No, I'm being told no.
[Laughter]
This is the way a living cell looks down a light microscope, and it's been filmed under
time lapse which is why you can see it moving. The nuclear envelope breaks down, the sausage
shaped things are the chromosomes, and we'll focus on them. They go through this very striking
motion that is focused on these little red spots. When the cell feels like it's ready
to go, it rips apart the chromosome. One set of DNA goes to one side, the other side gets
the other set of DNA, identical copies of DNA, and then the cell splits down the middle.
And again, you have billions of cells undergoing this process right now inside of you.
Now we're going to rewind and just focus on the chromosomes, and look at its structure and
describe it. So again, here we are at that equator moment. The chromosomes line up and
if we isolate just one chromosome, we're going to pull it out and have a look at its structure.
So this is one of the biggest molecular structures that you have, well at least as
far as we've discovered so far, inside of us. So this is a single chromosome, and you
have two strands of DNA in each chromosome, one is bundled up into one sausage, the other
strand is bundled up into the other sausage. These things that look like whiskers, that
are sticking out from either side are the dynamic scaffold in the cell, they're called
microtubules but their name is not so important, but what we're going to focus on is this
red region, I've labelled it red here, and it's the interface between the dynamic scaffolding
and the chromosomes. It is obviously central to the movement of the chromosomes. We have
no idea, really, as to how it's achieving that movement. We've been studying this thing
they call the kinetochore for over a hundred years, with intense study, and we are still
just beginning to discover what it's all about. It is made up of about 200 different
types of proteins, thousands of proteins in total. It is a signal broadcasting system.
It broadcasts through chemical signals, telling the rest of the cell when it's ready,
when it feels that everything is aligned and ready to go, for the separation of the chromosomes.
It is able to couple onto the growing and shrinking microtubules. It's transiently,
it's involved with the growing of the microtubules, and it's able to transiently couple onto them.
It's also a tension sensing system. It is able to feel when the cell is ready,
when the chromosome is correctly positioned. It is turning green here because it feels
that everything is just right, and you'll see there this one little last bit that's
just remaining red, and it's walked away, down the microtubules. That is the signal
broadcasting system sending out the stop signal and it's walked away, it's that mechanical.
It's molecular clockwork, it's how you work at the molecular scale. So, with a little
bit of molecular eye candy...
[Laughter]
We've got kinesins which are the orange ones, they're little molecular courier molecules
walking one way, and here are the dynein, they're carrying that red broadcasting system,
and they've got their long legs so they can step around obstacles and so on. So again,
this is all derived accurately from the science. The problem is we can't show it to you any other way.
Exploring at the frontier of science, at the frontier of human understanding, is mind blowing.
Discovering this stuff is certainly a pleasurable incentive to work in science, but most medical
researchers, this is, discovering this stuff is just steps along the path to the big goals
which are to eradicate disease, to alleviate the suffering and the misery that disease causes,
and to lift people out of poverty, and so with my remaining time, my four minutes, 0:09:32.090:09:38.370 I'm going to show you, introduce to one of the most devastating and economically important
diseases, which inflict hundreds of millions of people each year. So again, actually sound,
thank you.
[Background insect and nature sounds]
This parasite is an ancient organism. It has been with us since before we were human.
Famous victims include Alexander the Great, Genghis Khan and George Washington. This is the neck
of a sleeping child just after the sun has set, and it's feeding time for mosquitoes,
it's dinner time.
[Mosquito noises]
This mosquito is infected with the malaria parasite. Now mosquitoes are usually vegetarian,
they drink honey dew, nectar, fruit juices, that that kind of thing, only a pregnant female will
bite humans, seeking nutrients from blood to nourish her developing eggs.
[Rainforest noises]
During the bite she injects saliva, to stop the blood from clotting, and to lubricate
the wound. Because she is infected with malaria, she, her saliva also contains the malaria
parasite, so it rides in during the bite. The parasite then exits the wound and seeks
out a blood vessel, and uses the blood vessel, the circulatory system, as a massive freeway,
heading for its first target, the core of your body's blood filter system, the liver.
Within two minutes of the bite, the malaria parasites arrive at the liver, and sensing
its arrival then looks for an exit from the blood stream, and this is where malaria is
particularly devious because it uses the very type of immune cell that is there, resident
in the blood stream, the immune cell is supposed to remove foreign invaders like bacteria and
parasites, but somehow, we are not quite sure how, malaria uses a backdoor entry into
the liver tissue. Here is that immune cell. Malaria leaves the blood stream, and infects
a liver cell, killing one or more liver cells on its way. So again this is within a couple
of minutes of the mosquito bite. Once it's infected a liver cell, it takes the next five
or six days. It incubates; it copies its DNA over and over again, creating thousands of
new parasites, so it's this delay of about a week since you've had the mosquito bite
before malaria symptoms start to appear. The malaria also transforms its physical nature,
it's heading for a new target. That next target is your red blood cells.
[Zooming noises of red blood cells and parasites]
As part of its transformation, the malaria coats itself with a coating of molecular hairs
that act like a, like a Velcro to stick onto red blood cells, um, to the outer surface,
and then they reorient themselves and penetrate inside the red blood cell. This happens within
30 seconds of leaving the liver. This is actually an area of intense study, if we can stop this
process, we could, we could create a vaccine for malaria. Once it's inside the red blood
cell it can hide from your body's immune system. It then, over the next few days, devours
the contents of the infected cell, and creates more parasites.
[Underwater sounds]
It also changes the nature of the red blood cell and makes it sticky, so it sticks onto
red blood, ah, blood vessel walls. This gives the parasite enough time to incubate and grow.
Once it's ready it then bursts out of the red blood cell, spreading malaria throughout
the blood stream. Malaria victims suffer fever, loss of blood, convulsions, brain damage and coma.
Countless millions have been killed by it. This year between two and three hundred
million people will be struck down with malaria. Most people who die from the disease are pregnant
women and children under the age of 5. Thank you.
[Applause]