[APPLAUSE]
KAT ARNEY: All of that,
and I'm still amazed
I can find my shoes
in the morning.
I thought I would start
with a very brief reading
from my book, which
sets the scene
and explains why I set
out on this journey
and why the book is called
"Herding Hemingway's Cats."
So this is from
the introduction.
You don't have to read along.
It's fine.
So it starts, "it all started
with a photo of a cat.
I was hiding at the back
of a scientific conference
at the Royal Society
in London when
a cuddly looking cat
with unusually big feet
caught my eye.
'This is a Hemingway
cat,' said the lecturer,
pointing at the animal on
the large screen behind him.
They have six toes.
They're polydactyl.
Ernest Hemingway was
said to be fond of them,
and they still live on his
estate in Florida today.
And here, he poked
at the computer,
changing the slide
to one covered
with photos of misshapen human
hands, of polydactyl children
with extra digits.
It's the same genetic
mistake that causes them.
So looking at a six-toed
cat or a six-fingered human,
a natural assumption
might be that it's
due to a fault in a gene.
But it's not.
In fact, the cause lies
in a faulty region of DNA
that acts as a control
switch, normally
turning a gene on at the
right time in the right place
to direct the formation
of fingers or toes
as a baby or kitten
grows in the womb.
Not only that, but
the switch is miles
away in genetic terms from
the gene it acts upon.
Learning about the Hemingway
cats and their broken switches,
it got me thinking about my own
understanding of how genes work
and how I explain
it to the public
through my work as a
broadcaster and writer."
And so I wanted to write a
book about how genes work.
And so I traveled and Skyped
my way around the world,
talking to loads of
scientists that I know.
My background's in genetics.
And I said, I'm writing a
book about how genes work.
What can you tell me?
And pretty much all of them
said, well, when you find out,
let me know.
[LAUGH]
Which really set the
tone for the idea
that there's so much we think
we know about genetics and genes
and how our genes build
our bodies and make us, us.
But in fact, we
barely know anything.
And it is like
herding cats, just
trying to drag all these
ideas together and understand
what to make of them.
So I thought I would present to
you a little basic introduction
to genetics.
Has anyone got any
kind of background
in genetics, genes,
DNA of any sort?
OK, you can skip the first half.
And then I talk a bit
about some of the stories
that I uncovered in the book.
And there's all kinds
of tales in here.
It's all first
person interviews.
There's a few jokes,
all sorts of things.
So obviously I recommend
that you read it,
but I thought I'd talk
about a few of the stories
that I uncovered along the way.
So here we go.
(SINGING) Da da da da!
Pity my whimsy.
There we go.
So obviously, you
all work at Google.
What is the internet made of?
AUDIENCE: Cats.
KAT ARNEY: Cats.
[LAUGHTER]
Science is also made of cats.
But obviously with science cat
jokes, you can overdo them.
It also turns out that DNA
is made of cats as well.
So this is DNA.
You've probably all seen it.
It's the sort of
standard shorthand
for all science-y,
biology stuff.
But this is the stuff
of life, the instruction
manual in all our cells.
All of life has DNA.
It's made up of four different
letters, A, C, T, and G.
These are four chemicals
all strung together
in all kinds of
different orders.
And it's the cell's
instruction manual.
It tells the cell to do things.
This is a very basic cell.
Well, it's an egg.
But the best way to
think about cells
is that they're like
kind of fried eggs.
Right?
Stick with me.
Stick with me.
The bit in the middle
is the nucleus.
This is where the DNA-- not made
of cats-- the DNA made of DNA
is in the nucleus, and the
rest is called the cytoplasm.
And all your body
is made up of cells.
You are made of trillions
and trillions of cells.
You have skin cells,
you have brain cells,
you have fat cells,
you have toenail cells.
We're all made of
different cells.
But they all have
the same DNA in them.
And it's the
instructions in that DNA
that make your cells do what
they do and build your body.
So this is the
key thing to know.
When people start
talking about genes
and we hear about genes in the
newspapers and stuff like that,
people want to talk about
a gene for alcoholism.
Oh, there's a gene
for Alzheimer's.
It's the gene for
cystic fibrosis.
It's the gene for obesity.
No.
Genes are things that
make things in cells.
They're basically
cookery recipes.
So when you're trying to talk
about how our genes work,
it's always important
to remember,
genes are instructions
that make things.
And then it's how those
things in our cells,
in our bodies, in our brains
are all put together and work
that make us who we are, give
us the abilities and skills
that we have, and also
the diseases that we get.
So I'm going to do a really
tiny bit of molecular biology.
And I'm going to
apologize, because I'm
really bad at PowerPoint.
So please laugh appropriately.
So I'm going to explain to you
how genes work, and then we
can all go home.
Genes work like this.
You have DNA.
That's some DNA.
That's a gene.
So a gene is basically
an instruction
that is just a segment of DNA.
It's kind of a
recipe within a book.
All the DNA in your cells is
like a recipe book or a recipe
library, and a gene
is just one recipe.
This is the thing
that reads the recipe.
It's called RNA polymerase.
Reads the recipe.
(SINGING) Da da da da da!
It took me so long to
work out how to do that.
I'm really bad at PowerPoint.
I may even move on to, like,
a star fade at some point.
And it makes a
molecule called RNA.
So RNA polymerase makes RNA.
And that is the
message from the gene
that then a cell uses
to build something.
This is the chef that's
making stuff in the cells
from the copied
instructions in the recipe.
It's called a ribosome.
Reads it, makes something,
and it makes protein.
And proteins are the things
in your cells that do stuff.
So your skin is kind
of hard and solid
and keeps the outside
out and the inside
in because it's full of
a protein called keratin.
The cells in the
back of your eyeballs
can see because they have
proteins that can sense light
and can send those
messages to your brain.
All of our bodies are
made up of proteins.
Kind of all the
molecules as well.
But genes are the instructions
that tell your cells
to make proteins.
They're recipes.
So again, just to reiterate.
Genes are not things that
give you diseases or give you
traits.
They make stuff.
So a little-- a few
facts, because I
know you all like facts here.
Factual things.
So I'll have to keep
it nice and factual.
My favorite fact
about biology, you
have 2.2 meters of DNA in
every single cell in your body.
This is absolutely staggering.
I'm five feet tall.
Two meters is enormous.
It's very thin, but it's
two-- I mean, come on.
Who's slightly boggled by that?
[LAUGHTER]
Every single cell
in your body-- you
have enough DNA in your
body to go to the moon
and back 1,500 times.
I find this staggering.
More people-- I mean,
I'm a biologist.
I find this stuff cool.
Within that, you have three
billion letters of data,
effectively, of the A's, C's,
T's, and G's, the instructions.
It's a huge amount of data.
And within that are
the instructions,
the genes, that tell
your cells what to do.
So how many have we got?
Well, it was originally
thought that we
had something upwards of
100,000 genes to make a human.
God, we're probably going to
need a lot of genes, aren't we?
Because we're kind of cool.
Turns out we've got
about 20,000 genes.
We're clocking in somewhere
around fruit flies and nematode
worms.
So this was a bit
of a shock when they
sequenced the human genome.
They were like, wha?
Where are all the genes?
They did a bet.
They actually did a
sweepstake to make people
bet on how many genes
there were going to be.
And people started out,
like, 150,000, 100,000.
We were like, whew.
We basically don't really
have that many genes.
We use the ones we have in
very interesting ways, which
sort of proves it's
not what you've got,
it's what you do
with it that counts.
But we only have
20,000 genes or so.
And all of that makes you, you.
And in fact, the sum total
of your-- all your genome,
those phone books
full of information
that is actual genes is
really not very much.
I told you I really
wasn't very good at this.
Only about 2% of your genome
is actual, honest to God genes.
So this is the question.
Like, what's the rest?
Any guesses?
AUDIENCE: Cats
KAT ARNEY: Cats.
[LAUGHTER]
Not cats.
Good-- good callback, though.
The rest-- I mean, people say,
oh, the rest is just junk DNA.
It's just junk.
It's just there.
Is it just junk?
No, it's not.
So there are all kinds
of things in your genome
in between the genes that
are-- some of it is junk, true.
But there are things like
all the control switches that
turn your genes on and
off in the right time
and in the right place to make
you, you, and to make you work.
There are genes as-- well,
I said at the beginning,
there are genes that encode the
instructions to make proteins.
But there's also lots and lots
of genes that are just read
into that message, that RNA.
And that does stuff
in cells as well.
There's a lot we really
don't understand about that,
but it's a very
interesting area.
A huge chunk of your
genome-- and I'm
sorry to say this-- is
just dull and repetitive.
Same as like the actual work
of sequencing the human genome
is very dull and repetitive.
Most of your genome
is made up of things
called transposons or
repetitive elements.
These are long-dead
viruses or jumping
genes that somehow
got into our genomes,
got copied and copied and
copied and copied and copied.
Your genome is basically, a
lot of the time, full of crap.
And some of it is
actively harmful.
Some of it is garbage.
We have some things
in our genome
that are really not good for
us, and evolution is gradually
clearing them out away.
But a lot of the other
stuff, the junk that's
in our genome, people say, well,
why have we got it in there,
you know?
Everything must be
here for a purpose.
Well, these people perhaps have
a slightly religious agenda.
[LAUGHTER]
And they cannot comprehend the
idea that we can just have crap
in our genomes
that's just there.
I'm going to do a quick survey.
Hands up if you have
some stuff in your house
that is just there.
[LAUGHTER]
Because the effort of
getting rid of it--
if I had the world's most
neat, clean, tidy office,
that would be amazing.
But the effort of
actually tidying my office
is unbelievably hard.
It's much better just to,
like, put it all in a box
and just leave it there.
It's not hurting anyone.
It's not in the way.
If it starts to get in the
way or if it starts smelling
or I really need that box
for something else, sure,
I'll [INAUDIBLE].
But it's the same
with your genome.
Evolution is not this
perfect winnowing
engine that gets rid of
everything all the time
it doesn't need.
And I'm kind of sorry
to break it to you,
but you are not the
pinnacle of our species.
I mean, even though
you work at Google.
[LAUGHTER]
Sorry, guys.
You are not the bestest, most
fittest example of humanity--
[LAUGHTER]
--that could possibly be.
Evolution is a constant process.
So it's not perfect.
And we keep stuff in our genomes
that, you know, is just there.
It's not doing us any harm.
It's just there.
So I'm going to focus on
some things in our genomes,
the control switches.
Because there are some
quite nice stories here
that I cover in a couple
of chapters of the book.
Now the control switches
I'm going to talk about,
these are the things that
turn our genes on and off
in the right time and
in the right place
to make the tissues of our body.
And this is important.
Because as I said, all the cells
in your body have the same DNA.
They all have the same
instruction manual.
But the cells of your
body are different.
You have 200 more than-- way
more than 200 different types
of cells.
You know, hair cells, skin
cells, fat cells, liver cells,
kidney cells, all
these kind of things.
But you have the same
instruction manual.
So it obviously
figures that you have
to use your genes in different
ways, different types of cells,
to get the right outcome.
It's the same
thing as, you know,
if you're making a
glamorous dinner party,
you'll want glamorous
dinner party recipes.
Whereas if you
make a kid's party,
you want kind of a
kid's party recipes.
So this is the problem.
All our cells are not the same.
And this goes back right to the
very, very beginning of life.
You start life as
one single cell,
a fertilized egg when mommy
and daddy love each other very
much.
And you grow.
You grow into two cells,
four cells, eight cells,
a little football of cells.
You become a sort
of little bubble
of cells with a blob
in the middle of it
that is going to be you.
And those cells are the
stem cells that make a baby,
and they have to specialize,
they have to make decisions.
They have to go, are you
going to be head or tail?
Are you going to
be brain or skin?
Are you going to be
inside or outside?
Are you going to
be gut or liver?
All the way down to the
really finessed decisions.
Are you going to be that
bit of your fingernail,
or that bit of your fingernail?
And all of this is
determined by genes
turning on and off at the right
time and in the right place.
So how does that work?
Well, you can think
of this is a bit
like a kind of a genetic
switch, a control switch.
So here's our
representation of a gene,
the blue thing with the arrow.
People always draw
genes like this.
It's a gene.
It gets read that way.
That's why we draw
them like that.
The little purple thing near the
beginning of the arrow, that's
something called a promoter.
Now all genes have a
promoter at the start.
This is the thing that
says, here's the gene.
We start reading it
here in that direction.
Now just having a promoter is
not enough to turn a gene on.
You need a molecule, a
protein, a transcription factor
to come and sit on
that and say, OK.
We're here.
This is the start of the gene.
We're going to do
something here.
But that's still not
enough to turn a gene on.
So what you have is
a control switch.
That's the little
green thing there.
And you have other
molecules, depending
on the type of cell that it
is, that sit on those and say,
right.
We're going to turn this
gene on here in our cells.
And in other sorts
of cells, they'll
have a different suite of
these factors that turn genes
on in different places.
And ta-da!
That is enough to
get a gene going.
Now obviously that's
just one thing.
So that's only going to turn
that gene on in the place where
the green thing is happening.
Does this all make sense?
Yeah?
Good.
So of course, if you
want to turn genes on
in, say, different tissues,
if you need the same gene
to be switched on in the brain,
in the liver, in the kidneys,
in the lungs, but
not anywhere else,
you need a little
bank of switches
that all respond to
different factors that
are there in that tissue
at the right time.
So that's a really--
that's about kind of a year
and a half's worth of a genetics
and molecular biology course
there, guys.
So well done.
And now we get to the fun stuff.
This is Ernest Hemingway.
I love Ernest Hemingway
for many, many reasons,
mainly because God, that guy
could write a sentence that
punched you in the face.
But Ernest Hemingway also
liked several things.
So things liked by
Ernest Hemingway,
I have done a Venn diagram.
[LAUGHTER]
Ernest Hemingway likes fighting.
We know from books like
"Death in the Afternoon,"
he likes fighting.
He also liked fishing, mating--
[LAUGHTER]
--and all these
things come together--
[LAUGHTER]
--in cats.
I knew I'd get back
there in the end.
And specifically, these cats.
Now this is a
polydactyl cat, like I
mentioned at the beginning.
It has multiple toes.
You can see it's the
thumb there, bizarre,
three-claw thing.
So this is a polydactyl cat.
And Ernest Hemingway
had loads of these cats
on his estate down in Florida,
down in the Florida Keys.
And the story goes that he was
given one cat called Snowball
or possibly Snowflake--
the legend is
a bit uncertain-- by
an old ship captain.
Gave him a six-toed cat.
And Hemingway kind of
liked them because he
likes the sea and sea
captains, so he kept it.
And the story's about
why so many of the ships
had six-toed cats,
because they're
very popular all down the
eastern seaboard of the US.
Loads and loads of the
cats have six toes.
There's an idea
that maybe they're
better at catching mice.
You know, you've got kind
of big, extra paws, toes.
You can get them.
Important on a ship.
Useful.
If the ship's kind of
rocking about a lot and you
have a prehensile
thumb, you could
grab onto a rope or
something like that.
You just imagine this cat like--
[MEOW]
--hanging onto the rigging,
that kind of thing.
There are many reasons
why cats with six toes
may be useful on board ships.
The main reason, I think,
is probably this one.
[LAUGHTER]
Because, like, what's more
lucky than a cat with five toes,
right?
So let's look in a
little bit of depth
at the switches
that are responsible
for this particular phenomenon.
So this, this is the bit
of proper genetics here.
This is the part of
the cat genome and also
the human genome that is
responsible for building toes.
I mean, not specifically
building toes.
There isn't a toe
gene as discussed.
But there is a molecule, and
it's called sonic hedgehog.
Yes, after the
cartoon character.
That's that sort
of little SHH thing
where the green
arrow's pointing.
And that is responsible
for basically saying,
let's build some digits here.
Let's do something here.
Now sonic hedgehog is
used all over the body
during development.
It's used to build digits.
It's used to make
decisions in the brain.
It's kind of a
deciding molecule.
It decides things for cells.
So it gets turned
on in the brain.
Those are the blue
things called CNS.
Those are the Central
Nervous System switches.
It's involved in the
skin and the guts,
the epithelial linings.
Those are kind of
the orange switches.
But the one I'm really
interested in is the green one.
And that is the limb
bud switch which
turns on sonic hedgehog-- that's
the little blue patch there.
This is like the developing
pore of a mouse in the womb.
It turns on sonic hedgehog in
a little strand at the bottom
where the fleshy part of
your hand's going to be.
And it says, we're going
to make some fingers.
And these ones are going
to be, like, pinky,
fourth finger, third finger, all
the way through to the thumb.
It's sort of a
gradient that says,
we're going to do
fingers like this.
So it's a really
important switch.
And obviously when
it's faulty, you
end up with the
cells in the hand,
in the developing hand, just
kind of not knowing what to do.
They just start making more
and more toes or thumbs,
because they're just not
really sure what's going on.
And it's the same
mutation in cats
and a similar mutation
in polydactyl humans
with multiple fingers as well.
So these switches are
kind of really important.
And obviously, there's
an evolutionary advantage
to cats having six toes.
Because as I said,
on ships they're
perhaps better at grabbing on or
just that sailors favored them.
And who knows?
Maybe one day these cats with
thumbs may gain other skills
and possibly learn to
kill us as we sleep.
And I, for one, welcome
our feline overlords.
[LAUGHTER]
But there's an interesting
and more important thing here.
So these switches in the genome
are evolution's playground.
So we think about evolution
as very small changes.
You know, we're taught
at school that evolution
is very, very slow.
One change, and you
get a small thing.
Maybe a tail gets a bit bigger
or a neck gets a bit bigger,
or you get a bit more
spotty, or something.
Evolution is very
slow and gradual.
But as we've seen,
just one faulty switch
is the difference between
having five toes and six toes.
So small changes
in these switches
can make really big
changes to organisms.
And I'm going to tell you
about one of these stories now.
So I'd like you
to meet some fish.
We go from cats to fish.
And these are sticklebacks.
Anyone seen sticklebacks,
gone fishing for sticklebacks?
They're fish.
They're spiny.
So the top ones are
sticklebacks that
live in marine environments.
They live in the sea.
Now about 10,000
years ago, there
were lots of sticklebacks
like that living in the sea.
And they would always
swim up the rivers
to spawn and do whatever
it is sticklebacks do.
I mean, probably carefully
if you've got those spines.
I'll tell you.
So they swim up the streams to
go into fresh water to spawn,
and then they come
back down to the sea.
Now a bunch of
sticklebacks came really
unstuck in the last ice age
in that they got upstream,
and then they got stuck.
So you separated two
populations of sticklebacks.
So you've got the ones on the
top that are marine dwellers.
And over the course
of 10,000 years,
the sticklebacks in
the freshwater lakes
changed to be like
the ones below.
Now can anyone see the
difference between those two?
AUDIENCE: [INAUDIBLE].
KAT ARNEY: Slightly
bigger fins, yeah.
The key thing to notice a thing
that looks a bit like a willy
on the top one kind
of poking down.
It's not a willy, because
I wouldn't show you that.
In fact-- well,
that's coming later.
[LAUGHTER]
But that is some pelvic spikes.
So the sticklebacks that live in
the sea, they have these spiny
fins to fight off predators.
It's something like
kind of fembot,
like-- pu, pu, pu kind of thing.
They have these spiny
fins to keep them safe
because there's loads
of predators in the sea.
The sticklebacks that ended
up in the freshwater lakes
didn't have the same
predators, and they
don't have these spiny fins.
So a guy in Stanford
in the US called
David Kingsley got
very interested in this
and he said, well, what's the
difference between these two
fish?
Because to all
intents and purposes,
they're only separated
by 10,000 years.
That's not very long
in evolutionary terms.
And they kind of
look pretty similar.
So here's an X-ray
of these fish.
So the top one is
marine sticklebacks,
and the bottom one is the
lake-dwelling freshwater
sticklebacks.
They've got no bloody pelvis.
Their entire pelvis is missing.
So not just they haven't got the
spiny fins or their spiny fins
are a bit smaller.
The whole thing's just gone.
That is pretty radical.
And for that to happen in just
10,000 years-- which is like,
it's nothing in evolutionary
terms-- that is amazing.
And actually, it's down to one
broken control switch in a gene
called Ptx1.
Don't really need to know
what it does or what it's for.
But one single
change in a control
switch that turns a gene
on at the right time
to build the pelvis in the
sea sticklebacks, broken
in the freshwater sticklebacks.
No pelvis.
No pelvis at all.
Gone.
Vanished.
Gone.
It's absolutely incredible.
And what's even more
amazing is that you
can take that bit, that
control switch in the DNA,
and you can put it back
into freshwater sticklebacks
with no pelvis, and
they will grow one.
So you can see there that
little-- that shouldn't
have that bit there.
They've put that
control switch in there.
It turns the gene back
on at the right time.
And these fish, first fish of
their type for 10,000 years,
growing a pelvis and,
like, their spike things.
Who knows what they
thought of that?
Maybe they wake up like, whoa!
[LAUGH]
Whoa?
And this is not
the only example.
So David Kingsley's
looked at other examples.
For example, we have
a gene called Kitlg.
This is responsible for things
like pigment, pigmentation
in the hair, in the skin.
You get two different
versions of a control switch.
There's one letter
difference in this control
switch by the Kitlg gene.
One of them gives
you brunette hair.
The other gives you blonde hair.
That's one single letter
is the difference.
Now I grew up in
the '80s and I would
make a lot of blonde jokes.
And I-- I'm sorry.
I didn't know any better than.
But I know now.
But it's one letter
that's different.
And you know,
blonde jokes aside,
there are more
fundamental things.
Again, there's another
control switch.
One single letter
difference is the difference
between white skin
and darker skin.
Now it's not like an on/off.
If you've got this,
you're going to be white.
If you've got this,
you're going to be dark.
Because you know, we are more
than fifty shades of people
here.
But it's kind of
turning the dials.
It's ramping genes up and
down, making them more active.
You make more pigment
or less pigment.
And it's one letter in the three
billion letters of your genome.
Now as I was researching this
and kind of writing about all
of this, it was just
when all the race
riots were going on in the US.
You know, the police sort of
shooting unarmed black people.
And I sort of sat there and I
thought, this is ridiculous.
It's one letter in
our DNA, and people
have died for
thousands and thousands
of years because of this.
So anyway, that's
the philosophy bit.
And now here comes the rude bit.
So I don't know, ladies,
if you've noticed,
but if you've ever
had sex with a chimp--
[LAUGHTER]
--they don't call
you in the morning.
There are certain
species, mammal species,
things like chimps,
mice, tomcats, they have,
what's probably nicest to call
it, a promiscuous lifestyle.
They sort of prefer
the wham, bam,
thank you, ma'am kind
of school of procreation
rather than anything else.
They certainly don't spend
their Saturday mornings in Ikea.
I'm just about to
get divorced, so I
don't have to spend my Saturday
mornings in Ikea anyway.
Yay!
But what is different between
these species and human males
is that if you look in
the trouser department--
I think this is going
on the internet,
so I probably need to be
a bit euphemistic here.
But if you look on the
genital equipment of things
like the tomcat, the
mouse, and the chimp
there from left to
right across the top,
they have these kind of
spikes on their penis.
That's the technical term there.
Is this going to be
explicit content?
It's fine.
OK.
So they have what's
called penile spines.
And these are, for some
reason, meant to, like, grip
on if the lady's
running away going, you
never even bought me
dinner, that kind of thing.
But they're meant to
grip on and enable
the males to go for their sort
of fast and furious mating
style.
Guys, I'm assuming
that you guys don't.
If you do, you should
go and see a doctor.
And some human males do
have, like, little nodules,
and they're the
remnants of these.
But the key difference
here is that there
is a single genetic
switch that is
different between all the
species with spiky penises
and human males.
And it's a switch that controls
a gene called the androgen
receptor, which is a receptor
for the male sex hormone
testosterone.
You know, it makes you grow
your male characteristics,
and things like that.
And this one change
in this switch
is responsible for
this difference.
So you can tell a lot of
evolutionary just-so stories
about all these kinds of things.
One is maybe that some lucky
proto human developed this
in his genitals and
the ladies that he was
going with were like, oh, yeah.
[LAUGH]
I think I prefer that
to the spiky one.
Do you want to do it again?
And maybe that
encouraged pair bonding
and the more sort of
monogamous social relationships
that humans have.
I don't know.
Am I right, ladies?
I personally don't really
fancy a spiky boner.
Don't know about you.
[LAUGHTER]
So those are some stories
about the control switches
in our genomes and
how they can make
some really big differences
to the outcome of an organism.
The other thing I want to
really briefly touch on
before I finish is that I've
drawn a lot of pictures for you
of the idea of a gene as
this long, straight line.
I've got a gene, we've
got the switches,
and things kind of sit on
it, and it does this stuff,
and it's all very linear.
But as I said right
at the beginning,
you have two meters of DNA in
every single cell of your body.
That's two meters
of DNA in something
that's less than the size
of the head of a pin.
So biology doesn't
look like these kind
of nice, neat diagrams.
The DNA in your
cells kind of looks
like this, but much, much
more messy and compact,
and it's wrapped up around
all sorts of proteins
to keep it packed in there.
And you're like, wow.
How does anything find
anything in there?
And the idea is that our
biology is actually not
as neat and linear
as you might think.
You can see a diagram like the
one on the top and think, OK.
These factors find these
genes and turn them on.
Stuff's got to find each
other in this complete mess.
And sometimes it'll work,
and sometimes it won't.
And genes will go on
and genes will go off,
and you have to bring
all this mess together.
And I touch on it a
lot more in the book,
and I'd really encourage
you to find out a bit more.
But we are products
of probability.
This is a stochastic event or
random, I prefer to term it.
Scientists prefer stochastic,
because for some reason,
just saying, like, life's
kind of random upsets people.
This is a stochastic process.
Genes aren't exactly
switched on and off.
They're more like kind of
dials, suggestions, landing
platforms for the things
that make them work.
And with that in
mind, I'll tell you
a final story before
I finish, which
is about the wobbly worms.
So there's a chap called Ben
Lehner who works in Barcelona.
And he works with
these tiny organisms.
These are nematode
worms, C. elegans.
They're a millimeter long.
And loads of
biologists love them
because they are
completely stereotyped.
They do exactly the
same thing, same time.
They have an exact
number of cells.
It's about 1,000 cells.
And they all divide in a
completely programmatic way.
So you can start with one
fertilized nematode worm egg
cell, and you can watch on cue
as the cells pop into existence
and divide and specialize.
And they all have names.
Every single cell in
that worm has a name.
They're called things
like AB1 and stuff
rather than, like, you
know, Carrie and Doris.
But every single cell
in that worm has a name.
And the worms that he uses
are genetically identical.
They're like super clones.
They're all exactly the same.
And so you would assume that if
you damaged a gene or a control
switch or something like
that in one of these worms,
it would come out with exactly
the same outcome all the time.
And this is where it
gets weird, because you
have this gene, you
make a mistake in it,
half of the worms die.
Now that's weird,
because they've all
got mistake in that gene, but
only half of them have died.
So that tells you that there's
a whole bunch of buffering
going on in the genome.
And you know, like I say,
this is a stochastic event.
This is not a yes/no.
And it highlights that our genes
are not yes/no, deterministic,
on/off, make this,
don't make that.
There's a lot of
randomness in there.
Interestingly, if
you break two genes,
you can shift the balance.
You'll end up with
10 alive and 90 dead
if you look at
100 worms that all
carry this gene [INAUDIBLE].
And you know, if
you start breaking
more parts of the system,
you'll end up with all dead.
Biology is incredibly robust.
We wouldn't be
alive if it wasn't.
And the final thought
I will leave you with
is this, is that the more we
start delving into our genomes,
the more we
sequence, the more we
understand-- we're
now at this point
where we kind of
sequence all the things.
We're starting to sequence
more and more human genomes.
And we're discovering
incredible stuff.
We're discovering the fact
that each one of us is walking
around with about 30 genetic
faults that should probably
kill us, but they don't.
Because you've got
all this other stuff
that's going on and
buffering in your genome.
And that's what keeps us
alive, and that's amazing.
Your genome is amazing.
I hope you enjoy it, and I
hope you also enjoy my book.
[APPLAUSE]
MALE SPEAKER: Lovely.
Thank you, Kat.
We've got time for
a few questions
if anyone has questions.
You think of one.
I will kick off.
With the humans, we have
about 20,000 genomes.
And you said we're quite--
KAT ARNEY: Genes.
MALE SPEAKER: Genes.
I'm sorry.
And we're quite inefficient
in terms of, like, the baggage
that we store and stuff.
KAT ARNEY: Yeah.
MALE SPEAKER: So does that mean
animals which don't-- which
have a much faster,
shorter life span--
fruit flies and so forth--
are they more efficient?
KAT ARNEY: Yeah, broadly.
So fruit flies have
smaller genomes.
They sort of carry
less crap with them.
It is like the idea,
if you live in a family
home for, like,
60 years, you will
accumulate loads of rubbish.
It's broadly that kind of law.
And one of the most
incredible genomes
is the puffer fish, fugu,
the Japanese delicacy.
And that's got pretty
much all the same genes
that we have, but an
eighth as much DNA.
So that's really interesting.
And when people go, oh, yeah.
We need junk DNA.
We need it for all these things.
I'm like, well, you
don't need it pretty much
to successfully
build a vertebrate.
So it's an argument
that's still running.
MALE SPEAKER: Thank you.
All right.
Yes?
And if you can
repeat the question.
KAT ARNEY: Oh, OK.
Sure.
AUDIENCE: How do you
even count the genes?
How do you know
what isn't a gene,
[INAUDIBLE] to other genes?
KAT ARNEY: That's
a great question.
So how do we know
what a gene actually
looks like in the genome?
So this is the job of something
called genome annotation.
And there's all these people at
the Sanger Centre in Cambridge
and the EMBL and things
like this doing it.
So remember I said
that there's a promoter
at the start of a gene?
That's a really
characteristic DNA sequence
that you can spot it.
There's things like--
something called a TATA box.
And that's a run of T, A,
T, A. That kind of thing.
So you can spot those.
I don't want to go too much
into the molecular biology.
But you get little groups
of three DNA letters
that make the individual
building blocks of a protein.
So if you get a long
uninterrupted string of things
that you know are making
proteins, you kind of go, OK.
That's probably a gene.
There are some other
characteristics as well,
but it's-- and that this
is where it gets hard
because there's been this sort
of arbitrary cutoff for how big
a gene is.
So you go, OK.
It has to be over
a certain size.
It has to make a protein that's
at least this big to be a gene.
And now we're
discovering that there's
all these kind of
tiny little genes
that actually make proteins.
They're called smORFs,
Small Open Reading Frames.
And it's just because we didn't
just arbitrarily said, oh,
those can't be genes.
So you know, it's
like a fishing net.
You only catch
the size of things
that you think
you're fishing for.
And again, we're saying as
humans, these are genes.
And in fact, there's
a lot probably
that we don't know that's
doing stuff in the genome.
So it's an open--
an open question
about what's actually useful
and doing stuff in the genome.
Hi.
AUDIENCE: So my
understanding is that when
we're sequencing genomes,
we break everything up
into little bits.
And then we count
all the little bits
and we go, oh, they
probably go together
in this order as a rough.
How likely is it that
something will come along
and we found we've been
doing sequencing wrong?
Or how statistical are
measurements, I guess,
is the question.
KAT ARNEY: Oh, so this
is, how accurate is genome
sequencing if we're just
kind of ripping everything
up and sticking it
back together again?
You're looking for overlap.
I mean, the next
generation sequencing-- so
when I was first a scientist,
the way we sequenced genomes
was you'd start here and read a
bit, and then you'd start here
and you'd read a bit further.
So it was really--
you kind of knew what
you were patching together.
You looked for really big
overlapping bits of DNA.
The new generation of
sequencing kind of does take--
takes everything up.
It's like taking a book,
ripping it all to pieces,
reading it all at once, and
trying to assemble the words.
And again, you're looking for
multiple overlapping regions.
And yeah, it does come down to
how good your algorithms are.
And this is where the problem
is that so much of the genome
is repetitive.
that has been ignored.
And now people are starting to
talk about the platinum genome.
I had a lovely analogy.
[INAUDIBLE] [? Bernie ?], who's
one of the big sequencing guys.
He said, you know, for ages
we've drawn this map of Europe
that's like the genome.
And everyone's gone, oh, God.
I don't want to have to
do the fjords, you know?
[GROANING]
I'll just--
[MUMBLING] But now we're
having to do the fjords
because there's probably
interesting stuff in there.
Or we need to know
what's in there so we
know it's not interesting.
AUDIENCE: So given the fact that
we have relatively fewer genes,
but the total size of the
genome is comparable to--
and probably in the
larger end, does that
mean that the average
size of our proteins
is typically bigger than
those of other animals?
KAT ARNEY: Well, no.
I mean, we've basically
got mammalian genes.
So you know, there's
a pretty standard set
of genes and proteins that build
vertebrates, build mammals.
And our genes are broadly
the same as those.
There's nothing in our genes
that's particular to that.
Then it is in the junk,
in the control stuff,
and all the other stuff
that is special to us.
And it's quite an interesting
thing to get your head around.
Because obviously, we
basically share all our genes
with the chimp.
We are pretty much 99.9% chimp.
So the difference
between us and a chimp
must be that our
control switches,
our human controlled switches
in our-- rest of our human DNA,
whereas a chimp's got
chimp control switches.
So you have primate
genes plus humans
switches makes human, primate
genes plus chimp switches
makes chimp.
So the actual-- the suite of
genes is very, very similar,
but it's all the other
stuff that's different.
AUDIENCE: Hi.
So there's been quite a
lot of, like, studying
the genes of
[INAUDIBLE] and cloning
and [? oil ?] companies that
offer to read genes, DNAs.
But I was wondering,
like, at this point,
how far is science will
actually being able to,
like, later on in the
genetic material as like--
KAT ARNEY: OK, in
terms of, like,
editing and sort of
design-- is this the design
of [INAUDIBLE] kind of question.
How close are we to taking that
information, manipulating it.
AUDIENCE: Yeah, like-- or even
like if you get to know your,
like, genetic material,
is there anything you
can do about it at this point?
KAT ARNEY: Yeah.
Sure.
The answer broadly is no.
I need to be careful,
because Google own 23 of me,
don't they?
[LAUGH]
MALE SPEAKER: A tiny bit.
KAT ARNEY: A tiny bit.
So there's lots and
lots of organizations
that will sequence your genome
or at least look at bits of it
and say, OK.
You've got this, which is linked
to this tiny increase in risk
of x, y, zed.
There are a few diseases
that we know of-- things
like cystic fibrosis is
a great example-- that we
call the Mendelian diseases.
It's like it's one
gene, one fault in it
gives you the disease.
The faulty gene in
cystic fibrosis,
it makes a protein
that kind of shuffles
salt in and out of your cells
so you don't make mucus properly
and all this kind of thing.
Most diseases, things
like Alzheimer's, obesity,
characteristics like
intelligence, even
things like hair color,
skin color, weight,
all sorts of things, many, many,
many genes-- and it's about
variation, things being
dialed up and down.
And like I showed
you with it, you
know, stuff's just kind
of a bit random as well.
There's a whole random
element in there.
And that's what's been
really shocking about doing
the sequencing studies and
discovering that lots and lots
of people are carrying mutations
that should be manifesting
as a disease, but aren't.
So this is a problem.
If you have your
genome sequenced,
we now don't-- we're
starting to go, well,
we thought that if you had
this, you would be like that.
But now it's like,
well, if you have this,
you might be like that.
Might depend on a thousand
other variations in your genome,
and we don't understand
all that interplay.
So there's a huge-- I would
recommend you read my book--
[LAUGHTER]
--because there's a
huge chunk in there
about how people are
trying to unpick this
and trying to understand
how we integrate
all the information in the
genome, not just one gene.
And this is where it comes
on to the sort of designer
baby genetic
manipulation question.
Because you know, there's
all these techniques
you might read about the
papers called CRISPR and things
like that where you
can cut up bits of DNA
and manipulate them
and chop stuff around.
For some characteristics,
for maybe these one gene,
one disease kind
of characteristics,
I think that could be
incredible technology.
Real life-changing technology
for families that are affected.
Whether you're saying, OK,
can I do a bit of chopping up
and make a more
intelligent baby,
there's so much we don't
know about the genetics
of intelligence,
and the huge chunk
of environment,
lifestyle, upbringing
that comes on top of that.
So I think engineering
more complex traits
is going to be incredibly
hard, and you're probably
better off just having
sex with a clever guy.
[LAUGHTER]
AUDIENCE: In terms of the
nature-nurture argument,
my understanding of epigenetics,
which is very basic,
is that you can pass
the grandparents' genes
through to the grandchildren.
If the grandparents were obese,
that might get passed down.
Is that something
that is-- where's
that at in terms of science?
KAT ARNEY: So in terms of
where the silence is with that,
it's a little bit shaky.
So the idea of, this
is-- epigenetics
is a very, very misused and
incredibly abused phrase.
It's so abused, the poor
thing needs therapy.
This is-- epigenetics
is basically
describing how your genes
are used differently
in all the cells of your body.
Like I said, you've got the
same DNA in all your cells.
You need to turn
genes on and off.
That's epigenetic.
It's in addition to the
DNA, to the genetic code.
So that's fundamentally
what epigenetics is.
The kind of stuff that the
papers get very excited about
is the idea of
transgenerational epigenetics,
that something that happens
in the DNA of a grandparent
could get passed on to
their egg or sperm cells,
and then into the
next generation.
And this isn't
changes in the DNA.
This isn't mutations in the DNA.
This is the sort of
information about stuff
that's happened
in a lifetime that
has affected how the genes
work that then get passed on
down the generations.
And in humans, the evidence
for a lot of this is sketchy.
It probably does happen, but not
in the way that people think.
And there's been a couple
of really exciting papers
just in the past couple
of months suggesting
that maybe tiny little
fragments of RNA
might be responsible for
transmitting this information.
But it's a very, very new field.
And actually, when
I went to talk
to all the researchers
I was talking to,
I asked them, what's cool?
What's interesting?
And then I said last
of all, what's weird?
You know, what makes
you think evolution,
go home, you're drunk?
And so many of them said,
transgenerational epigenetics.
It's like it's really
the frontier about how
your lifestyle, things
you do in your lifetime,
can they get passed on
to the next generation
and the one after that, and
potentially even further?
And there's a whole
chapter about it--
[LAUGHTER]
--in the end of my book.
Read my book.
MALE SPEAKER: [INAUDIBLE].
AUDIENCE: So this
is [INAUDIBLE].
How much information about
creating a human is in the DNA
compared to-- in sort of
[? transient ?] in living
humans?
Or if I had just human DNA,
would I need a human egg
to make a human?
Or if I had, like,
T-rex DNA, would I
need a T-rex to make a T-rex?
KAT ARNEY: That is a
really great question.
If you had human
DNA and you put it
into, like, a primate egg or
any-- anything, into anything--
the problem is that life is
a kind of a slippery concept.
So life is not
just the molecules.
Life is not just DNA.
All cells, all living things,
come from existing cells.
So you would definitely
need to take the DNA
and put it into something.
I mean, this is what Craig
Venter is trying to do,
and he's doing it with,
like, very simple bacteria.
Synthesizing DNA, putting
it into a hollow cell.
And everyone goes, oh, my God.
He's created life.
We're playing God.
It's like, eh.
He still took some DNA and
put it into, effectively,
a living cell.
In terms of whether the switches
and stuff would all work,
some of them probably would.
Some of them probably wouldn't.
You can take, say,
a human chromosome,
and you can put it
into mouse cells,
and it will start working fine.
And there's a really
interesting model of,
I think, Down
syndrome that's based
on putting a human
chromosome into mouse cells.
So yeah, some of it
would probably work.
I don't know.
I've got time.
I'll write a grant.
I'll let you know.
MALE SPEAKER: Good.
Down over there.
AUDIENCE: Hi.
You mentioned
[INAUDIBLE] mutations,
and also that how our
shared DNA with a chimp
is incredibly similar,
[? and the only ?]
real difference
control switches.
Roughly, how many
of those control
switches would have to
go wrong for someone
to give birth to a chimp?
[LAUGHTER]
KAT ARNEY: Also a
fantastic question.
How many control switches--
MALE SPEAKER: [INAUDIBLE].
[LAUGHTER]
KAT ARNEY: How many controls
switches in the genome
would we have to change to
turn a human into a chimp?
[SIGH]
Probably not that many.
Well-- and we are extremely,
extremely similar.
And it's probably a few of
the key developmental genes.
So some of the brain
ones, obviously
like the hair and face thing.
The bony penis business.
Actually, there's a
really interesting story
that I had to take out of
the book about this woman
in Stanford who's discovered
that a lot of the switches
responsible for the shape
of human faces compared
to chimp faces are derived from
long dead viruses in our DNA.
So it's like,
literally these viruses
are the things that have made
us humans compared to chimps.
So I reckon if you started
knocking out loads of those,
you would start to get some--
back towards something that
looked more like a chimp
and less like a human.
I must publish
that at some point.
But yeah.
MALE SPEAKER: Yeah.
We'll take one more question.
The gentleman behind there.
AUDIENCE: Just going back to
the Mendelian diseases, which
I presume is your
repressives, dominant gene
stuff we learned in [? GCSE ?].
One in four chance of
parents, blah, blah, blah.
What makes it easy or
not easy to track down
the gene responsible for that?
I mean, we've got cystic
fibrosis and sickle
cell and [INAUDIBLE].
Is it just if you get enough
sample sizes [INAUDIBLE]
with it and without
it, you can find it?
Or some diseases, you
find them [INAUDIBLE]?
KAT ARNEY: Yeah.
So some of the--
a lot of the genes
that we've known
about for a long time,
they were really done the hard
way by tracking pedigrees.
But it's still the same about
taking sections of people's DNA
and reading it and comparing.
And there's sort of
various mapping techniques
that you can do.
So all through
the '80s and '90s,
people were sort of
homing in on regions
by looking for regions that
were similar between people
and regions that were
different, and going, OK.
All these people
with this disease
have broadly this area
that's all similar,
so it's probably in there.
And it took years and
years and years and years
and years and years.
And then with the sequencing
revolution, all you do
is you take someone
who's got it,
takes someone who hasn't, or a
bunch of people who've got it
and a bunch of people
who haven't, and sequence
them enough, and you'll
probably find some differences.
And then because of what we
know about what the genome looks
like, we have quite a good map.
You can go, OK.
If this is a syndrome
that's involved
in the shape of the
face, perhaps there's
a gene that's involved in
cartilage growth or something
like that.
So you can make some
pretty sensible deductions.
What gets more
challenging is when
you're looking for the
more subtle variations.
So I work for
Cancer Research UK,
and we do a lot of these
studies on cancer risk.
And you have to take tens
of thousands of people
and look for these tiny
variations between them,
and take 40,000 people
with cancer, 40,000 people
without cancer-- and it's got
to be the same type of cancer--
and say, OK, broadly, what
marries up between having
it and not having it?
And it's like--
it's a risk thing.
So it's starting to get very
hard to find these variations
and to find new genes.
And people are doing bigger
and bigger and bigger studies
and finding less
and less and less.
And I think that's
probably limited benefit
to be found from
keeping pursuing
those kinds of
studies, personally.
MALE SPEAKER: Well,
we'll leave it there.
Please join me in
thanking Dr. Kat Arney.
[APPLAUSE]
