We're all human, and, yet, we all look different.
Now, a lot about the way we look is down to our DNA,
as we can see so brilliantly with these identical twins.
From eye colour to hair colour, to dimples, to height,
each pair of twins looks very similar.
But look a little more closely and you'll see
that each person here is unique.
In this lecture, we'll explore how much of the differences
between us are down to genes, and how much is due
to everything else.
We'll be looking at what makes you unique.
I'm Professor Alice Roberts.
Welcome to the third of this year's Royal Institution
Christmas lectures.
And this lecture is all about us as a species.
It's all about human diversity.
But, first, let's start off with a different species,
which is very diverse indeed.
If you stand here.
So, we've got an amazing range of different dogs here,
and the astonishing thing about this is that they are all dogs.
They all belong to the same species, and, yet, they look so incredibly
different from each other.
We've got...we've got a great Dane, we've got a little shih tzu,
and a tiny, little miniature dachshund.
Now, isn't it amazing that there's all that variation in one species?
Humans first started domesticating dogs about 30,000 years ago,
when our ancestors were hunter-gatherers,
and, then, over thousands of years, we've somehow moulded
all of these changes.
So, we've bred dogs that are really good at going down burrows
and chasing animals, like the dachshund,
and this is all down to us interacting with this other species.
Now, to explore this diversity and how it comes about in more
detail, I need to introduce one more species, and my friend,
geneticist Professor Aoife McLysaght.
APPLAUSE
I wasn't entirely clear if you were referring to me
as the additional species, or this beautiful chihuahua in my arms.
But this chihuahua, of course, was bred as a companion dog,
and you can see he's very, very cute, and dogs are especially
interesting in terms of genetics, because this huge diversity
that we can see in front of us is actually down to
quite a small amount of genetic diversity.
They are, after all, just one species, and that makes it much
easier to be able to figure out how the genes contribute
to the changes that we can actually see on the outside.
So, for example, this little chihuahua, and other miniature dogs
like this, the size variation is largely down to
just changes in just one gene.
Now, we're actually able to understand the genetic basis
of some of this. Yeah, so, many of the origins of these traits have
been traced genetically, so we can get a real handle on how variation
in our genes contributes to the kind of variance that we can see.
So, let's have a think about how all of this variation comes about.
But, for now, let's say thank you very much to our
brilliant dog line-up.
APPLAUSE
So, all those differences have been bred into different breeds of dogs
by breeders choosing dogs with particular traits
and then breeding them on to the next generation.
That's something called selective breeding.
It's what Charles Darwin called "artificial selection".
And he imagined how he could continue thinking about this to see,
well, does this happen in nature as well?
How do we get natural selection?
And, to really explain this, we're going to play a game
with this demo, and we need two volunteers.
OK, let's see.
Yes, you there in the blue jumper. Lovely Christmas jumper.
Come on down. And I'll also pick one there as well. Great. APPLAUSE
Freddie, lovely to meet you, Freddie. What's your name?
Rebecca. Rebecca.
So, what you see beside you here are two habitats,
and you can see very quickly that this is a mainly orange habitat.
The floor is orange, and it's filled with these balloons,
which are mostly what we're calling orange pebbles.
And, over there, we've got a grey habitat with grey floor
and grey pebbles.
But, in amongst the pebbles, there is something else.
So, here we have a mouse,
and there's orange and grey mice in each of these habitats,
and, so, we're going to put these in there,
and, Freddie, and... Freddie, what we didn't tell you
is that your job is to actually be a predator.
You need to catch some mice, and you need to catch some mice as well.
So, you're going to have to go in there, and I want you to catch
mice but not pebbles, so if you can go around the back.
Just the ones with faces.
Yeah, so, only the ones with faces we're interested in.
Go round the back, we'll let you in.
Yeah, so don't start catching mice yet, because that's far too easy,
actually. Yeah, let's make it more energetic.
Yeah, we need to make something a bit more difficult for you.
LAUGHTER
So, on our marks. Well, we'll count down.
ALL: Three, two, one. Go!
JAUNTY MUSIC PLAYS
BOTH: Three, two, one. Stop!
APPLAUSE
OK, you can come out.
OK, you can come back out.
How was that? OK, let's have a look.
Well, that's a mouse.
These are pebbles, so we'll put those back.
What have you got in your box?
We've managed to catch four orange mice, and just one grey mouse.
Freddie managed to catch one of each.
So, what did you think, Freddie? What did you think of trying
to catch the mice in there? What was it like? Hard.
Was it hard? Was either colour easier?
Not really, no?
What about you over there?
Orange was easy.
It was easier to see the orange on the grey background?
Yeah, you were going after the orange ones, weren't you?
Yeah, and this is kind of what we expect.
We see this, that, naturally, in parts of the world
where we have, kind of, black rocks, you tend to find more black mice,
and in parts of the world where you have these golden, sandy rocks,
we tend to find these yellow, sandy-coloured mice,
because what we expect, especially in the grey habitat over there,
the orange mice were picked off quite easily
by this fierce predator, and...
..and the grey mice actually have survived to live
another day and to pass on their genes.
But we did ask you to be a predator. We did.
You haven't quite finished the job, have you? No.
Could you stomp on those balloons for me, please?
Do you want to have a stomp? Yes! Yeah! APPLAUSE
Thank you so much.
So, artificial selection has created all the dog breeds
that we see today.
Natural selection picked off some orange mice in that demonstration,
and natural selection has also acted on us humans as well.
So, our species originated in Africa, hundreds of thousands of
years ago, but, then, we spread out of Africa and colonised the globe,
so, we encountered all sorts of different environments as we went.
And there are lots of ways that humans can
fit into different environments.
We're quite clever, so we can create culture,
and that can help us.
So, if we move into a cold place, we might make ourselves
warm clothes to put on.
There's also physiological adaptation, and that means
that your body can get used to an environment
over your lifetime, but you don't pass those kind of changes
on to your children.
So, natural selection is when there is a genetic difference,
generation by generation, and we can see some
great examples of that in us humans.
And one really good example comes through the variation
that we can see in skin colour,
and it tends to map on to geography.
Now, most of us tend to have a fairly consistent skin colour
that we've inherited from our parents and from earlier ancestors.
So, over most of your body, your skin colour is fairly similar.
But I want to introduce you to somebody now who's got very striking
differences in skin colour across his body,
and he is fashion model Bashir Aziz.
APPLAUSE
Bashir, hello. Can I get a spud?
Thank you.
Bashir, you've got a really striking look.
You've got two completely different colours of skin, and hair as well.
Yeah. So, how long have you had that? Were you born like it?
Yeah, all my life. So, that's what I've known.
So, across your body, you've got areas, and obviously we can see
on your face you've got areas of quite pale skin,
and then dark skin as well. Look at your arm there, yeah.
So, you've got a real mixture. Yeah.
So, we can actually have a look and see how much skin pigment
you've got in different areas.
So, we can use this instrument here.
So, yeah, have a look at the back of your hand there.
And...there we go.
So, that says you've got 70% skin pigment on that area.
Let's have a look at areas of your skin that are pale, then.
Can I...can I try it on that area there? Yeah, of course you can.
If I just pop it on there, it should just work.
I mean, look at the difference there. That's astonishing.
So, where you've got pale skin, there's only, what, about 9%...
9%. ..pigment, so, a really, really big difference.
So, Bashir, I've got slides here of pale skin,
rather like the pale areas you've got, and then dark skin as well,
and you can see that they're very different
when you first look at them. Yeah. And this difference
is all to do with the skin pigment melanin,
and there are very few granules of melanin in this skin.
But you can see, in this section here, all of those cells completely
packed full of lots and lots of melanin granules.
I'm going to try it on me as well.
Go on, go on. I want to see, I want to see what I've got.
I've got a... There's a little bit of melanin there. Yeah. 19. 19.
There you are. Which is my hand, though, so it is exposed to the sun
quite a bit. That's all right. Yeah.
So, do you notice any difference between your dark skin
and your lighter skin? What, as in, like, naturally?
When you're exposed to the sun, do you notice any difference there?
Do I see any difference? Yeah.
No, I don't feel a difference. I don't notice a difference.
I just walk the walk and talk the talk. Yeah. I would like, say,
put a little sunscreen if it is very, very, very sunny.
So, it's interesting, because the difference in pigment
and the kind of pigment that's there to begin with anyway gives us
a clue as to why we've got this colour in our skin.
Yeah. And it is to do with sun protection.
So, in fact, your dark skin's giving you some pretty significant
sun protection here.
And Bashir's dark skin is coming out as about factor 20 sunscreen.
Naturally. So, you've got your own, natural sunscreen.
Oh, perfect, lovely. And if you have got very pale skin,
of course, you have to put sunscreen on if you go out
into bright sunshine, because you could
burn your skin, and every single episode of sunburn means that you
have a higher risk of developing skin cancer.
That's the seriousness of it a bit later on.
Bashir, thank you so much. Thank you for having me. Thank you.
APPLAUSE
So, that connection between skin colour and sun protection gives us
a clue as to how it evolved in humans as well.
So, our ancestors, who expanded out of Africa, would have all had
dark skin. So, the first Asians, the first Europeans
would all have had dark skin.
And, in fact, it's not until much later that some mutations started
to pop up in genomes so that skin started to get a bit paler,
particularly in very, very northern areas,
where the sun just isn't as bright as it is in the tropics
and around the equator.
And, in fact, we still see these patterns of skin colour today.
So, we still see that people whose ancestry is predominantly
from those sunnier places of the world tend to have darker skin,
and people who've got more ancestry in the far north
tend to have paler skin as well.
Well, next, we're going to look at another adaptation,
another way that natural selection has acted on humans,
but, this time, it isn't to do with interacting
with the environment as we find it, it's about interacting
with an environment that we've actually changed.
And it's about the beginning of farming.
I'd like you to gently give
a round of applause for Jade the cow
and her calf, Hazel,
who are going to come on now.
Oh, she's lovely.
Hello, Jade.
Hello.
So, Jade is a Dexter cow, isn't she? Yes.
And this is her little calf. Yes.
Yeah. So, obviously, calves drink their mother's milk,
and when our ancestors started farming and they started
domesticating cattle, they could keep cattle
for their meat, of course, but also for their milk.
Now, we want to demonstrate some milk here, so I want a volunteer
from the audience who's going to come down and milk Jade.
Let's see, who shall we have?
Another fantastic Christmas jumper, I think.
Just there, yes. Come down.
Yeah.
And what's your name? Nam.
Nam. Do you want to come and have a go at milking, then?
Yes, please. I think Felicity will help you.
Look, we've got a milking stool for you. So you can either sit
on the stool or you can lean down, and gently squeeze and pull,
like that. OK.
So, this is what our ancient farming ancestors had to learn to do,
just what Nam's doing right now.
There's a bit of a problem here, because it isn't so easy to drink
milk, and there's a clue to that in genetics. Yes, there is.
So, the main sugar that we find in milk is called lactose.
You see this lactose here.
And that's actually quite a hard sugar to digest.
It's a very big sugar, and, in order to be able to digest that,
it needs to be broken down.
That gets broken down by an enzyme,
and I need a volunteer to help me demonstrate what's going on.
So, let's see...
Yes, you at the back with the beautiful jumper
with the red stripe on it. Come on down.
Catherine, lovely to meet you.
So, Catherine, you are now going to be an enzyme
because we have enzymes which break down these things that we eat.
So, you're going to wear this, please. And if you could
come around here. What the enzyme does... If you come over here.
What the enzyme does is it breaks the lactose into smaller sugars,
so you can do that by turning this.
Yeah, so, that's the way it works. But stop for a second
because the enzyme doesn't just come from nowhere.
The enzyme is produced by a gene - that's me.
And the enzyme is only produced when the gene is switched on,
so, when you're a baby, this gene is switched on,
and, in this baby calf, this gene is switched on,
so the enzyme can go ahead. Yeah, keep... So, now the enzyme
is working, working, working, and it's breaking down this lactose into
smaller, simpler sugars that we can actually digest without any problem.
So, this is what this lovely, little calf has,
and it's what all baby mammals have.
But, then, at a certain point, what happens is the gene switches off
and the enzyme switches off.
Very good. And, so, this is what normally happens,
but is there anybody in this room who can drink milk and it's not
a problem? Lots of you, lots of you.
And including some adults as well.
That's because, in many humans, there's an adaptation to dairy
culture which means that the gene stays on and the enzyme keeps going,
and you're still able to break down this lactose sugar
well into adulthood, in fact, for the rest of your life.
And, when we look at what parts of the world this happened in,
it happens in parts of the world where we have dairy culture.
It happened in dairy cultures in Africa and in Europe.
So, thank you so much.
I'll switch off the gene now so you can have a rest.
Thank you so much. You were a wonderful volunteer.
Thank you. APPLAUSE
Oh, my goodness.
That's wonderful. And Nam did an absolutely brilliant job.
Thank you very much, Nam. Well done. Thank you.
I have never milked a cow. Have you ever milked a cow?
I don't think I have. Nam just did. Well done, that's impressive.
Thank you. Thank you very much, Jade and Hazel, as well.
Thank you.
APPLAUSE
So, this adaptation to drinking milk that appeared in our farming
ancestors then spread so that most of us in Europe can now...
..can now drink fresh milk.
And the way that that gene spread is through people
moving, through migrations.
And what we know is that, throughout history,
there have been big migrations of people,
and people have just kept moving,
and that has spread different characteristics around the world,
and that spreading keeps on going.
It's interesting that the ethnic groups that we can spot today,
and we can...we can sort of say one population looks a bit different
from another population, that's just a snapshot in the here and now,
and those ethnic groupings are different from what they were
a few thousand years ago, and they'll keep changing
because we humans keep moving and we keep mixing ourselves around.
So, we've got an illustration here of just some of the global
connectedness of everyone in this theatre tonight.
When you got your tickets, we asked you where your parents
and your grandparents came from, and we've mapped those connections
here. So, the centre of it all is, of course, this lecture theatre
in the Royal Institution in London.
This is just a snapshot of where you are this evening.
But here are all your family connections around the world,
to North America, to South America,
to West Africa, over here to Southeast Asia and East Asia,
and down to Australia as well.
So, what a wonderful image of global connectedness.
Thank you very much.
APPLAUSE
We've looked at some variation in humans that we can explain
through adaptation, and that we can experience
ourselves. We can look at our own skin colour, we can see differences
in skin colour around us, but there's another adaptation,
or another gene variant, that we want to introduce
to you now, which is a bit more hidden,
and we'll need some volunteers to help us show it as well.
Yes. So, this is something that is very much hidden,
so, let's see... I'll pick somebody.
Yes, you are very enthusiastic there.
Yeah, the boy with the lovely Christmas jumper.
How many do you want, Aoife? We need six, so you pick three,
I'll get three. OK. Right, I've got two.
All get close together into a line, shoulder to shoulder. Yeah.
What a lovely group of volunteers. APPLAUSE
Alice, I'd like... Alice, I'd like you to join in this one as well.
You can be our seventh volunteer. Yeah, yeah, I owe you one.
So, what I'm going to do now is I'm going to ask you to taste
something, OK? So, you're going to get a piece of paper.
If you just stick out your hand, you're going to get
a piece of paper. Just hold it in your hand for a moment,
and then I'm going to ask you to just place it on your tongue.
You're not to chew it or swallow it or anything.
There's going to be a mix of flavours.
So, some of you are going to taste something,
and some of you are not going to taste something.
OK.
Let's see.
Ah, there's a nasty reaction over there. What do you think?
Oh, my God! Take it out of your mouth again. That's disgusting!
And it... Yeah. So, who else thought it tasted disgusting? Ugh!
Did you get any taste? Yeah. You got a taste.
What did it taste like to you? I don't know, like broccoli.
Like broccoli? Interesting. What did you think?
I didn't taste anything. No taste.
But you thought it tasted horrible. I thought it tasted like soap.
Like soap? So, this is interesting, because we actually have genetic
variation of our taste receptor genes.
You all got the same piece of paper, but some of you could taste it and
some of you couldn't taste it,
and that's because we have different versions of a gene that allows us
to taste this bitter flavour or not.
But you seemed to think it was particularly horrible, did you?
So, I mean, maybe there's something I can show you here that might cause
you some dread.
LAUGHTER What do you think?
Do you like sprouts? No!
Cos you can taste the bitterness in them.
But thank you very much, wonderful volunteers.
Yeah, so we've seen a few examples of genetic variation.
Geneticists in particular are totally obsessed with variation.
We want to understand how the differences that we see
between us are related to differences in our genes.
This works quite differently in different cases.
So, for example, for height, the height that you will grow to
as an adult is really strongly determined by your genes.
It's really a strong effect.
Of course, what you eat and how much you eat is going to contribute
to that, but if I wanted to guess your height as an adult,
I would look at your parents, and that'd be a fairly good guess.
But there are other things which, even though there is a genetic
influence, it's really not that strong, there's something
else that comes in as well.
So, can you please raise your right hand if you are right-handed?
OK, that's really a lot of people.
Can you please raise your left hand if you are left-handed?
There's a few. OK, so when did you decide to be left-handed?
You never decided. It's a trick question, of course.
So, it's a strange one, because, even though
it's only partly genetic, you are also born that way.
So, in terms of whether you're left-handed or right-handed,
this is a really good example of where genes and chance
come together to make you what you are.
And we're going to represent that here
with this kind of obstacle course.
So, this obstacle course we've got here is representing the process
of development, so that's you growing in the womb.
And, if we imagine, we've got the start here, which is the start
of development, and, at the end, you either end up right-handed
or left-handed. So, if this one individual went through this process
of development... I have one individual in the shape of one
yellow ball. ..they might end up left-handed or right-handed.
We can't tell at the beginning, but let's see what happens.
Let's see. We'll watch it go down.
So we can't actually predict what side it will end up on.
But this one and ended up on the left, so this individual ended up,
let's say, left-handed.
But if we have somebody else with exactly the same genetics,
they might turn out differently.
So, this person ended up right-handed, and we can do
a few more, and we can do a few more.
I'm going to tip all these balls in and we'll see what happens.
Nice and easy.
OK, so, in this case, even though everybody
here has the same genetics, has got the same obstacle course,
a lot more turned out right-handed than turned out left-handed.
So, on average in the population,
90% of people are right-handed,
and only 10% of people are left-handed,
and, so, the genetics works a bit like this.
So, your genes set up a probability, but they don't determine exactly
how you're going to end out. No, they don't. You know, we might
think about something as normal or something as not normal, but that's
really not the way it is. Yeah, you've got two outcomes here.
One of them is more probable than the other one,
but you can't say that being right-handed is normal
and being left-handed is abnormal. No. But there's other things
that have similar genetics to this,
and one of those is sexual preference.
So, usually, men are attracted to women,
and women are attracted to men, but sometimes it's not that way,
and the genetics, actually, is very, very similar,
the percentage is very similar,
and we have a similar situation that the genes determine the shape
of this obstacle course, and sometimes it'll go one way,
and sometimes it'll go the other way.
So, your genes aren't completely in control.
There's a lot of room for chance as well. Yeah, yeah.
And, in fact, in our own bodies, we see the way that having the same
genome - for instance, on both sides of your body -
can produce slightly different effects.
Yes, and you can see an example of that by looking in the mirror.
And, for this, I will need another volunteer,
and I'll need somebody who is very good at staying still.
Who can be very, very, very still?
So, here is somebody who's very nice and still.
Yes, and with a beautiful jumper. Yes, you.
OK, so I'm going to ask you to do something.
Come round this side of the table. So, what's your name?
Kam. Kam, it's lovely to meet you.
So, I'm going to ask you to sit your head in your hands
like that, right?
I want you to keep your head as straight as possible and looking
straight at that camera. Now, we all have quite symmetric faces,
don't you think?
But there are little asymmetries that we can't even notice most
of the time, and those asymmetries are due to that kind of chance
in development that we just mentioned earlier.
So, if we look at this picture of Kam, we can see she looks
very symmetric, like all of us do, but she probably has some
small, little asymmetries.
So, if we just take the left-hand side of Kam's face and flip
it over and make a magic mirror image, and then we move
that over to the left here of the picture,
and we'll do the same thing with the right.
So we'll take the right-hand side and flip it over.
OK, so, now, keep looking exactly straight.
And, so, you can see here, on the left we have the left-hand
side of Kam's face made symmetric, and the right-hand side of her face
made symmetric, and they look a bit different, don't they?
So, it almost looks like Kam
is her own identical twin or something.
But just look at me without moving your head, without moving your head,
and can you look at Alice without moving your head?
LAUGHTER And back at me. And look back at Alice.
OK, thank you very much. You were wonderful.
Aoife, that was an example of how a genome can play out
slightly differently in one side of your face compared
with the other, but, sometimes, we get the same genome
in different individuals.
Otherwise known as... BOTH: ..identical twins.
And we have some twins who are here this evening
who have kindly agreed in advance to do some experiments with us.
So, if you could please come down.
We have Ronnie and Ritchie, and Noah and Harris,
and Rosanna and Caitlin.
APPLAUSE
OK.
OK, so, which one of you is Ronnie and which one's Ritchie?
I'm Ronnie, he's Ritchie. OK, thank you.
So, what we're going to ask you to do is to put your hand
into this bucket of ice water and to keep it there
just until it feels uncomfortable,
OK? So, you're going to take it out as soon as it feels uncomfortable.
And, because we want to compare you, and because we don't want you
to know what's happening with the other twin, we're going to
ask you to put on those ear defenders so you can't hear
what's happening around. So, I'm going to go behind you,
and I'm going to start these stopwatches, and you can see me
starting the stopwatch, and that's when you're to put your hand in, OK?
So, put the ear defenders on and we'll get ready.
OK, ready? Go.
So, while, Aoife, you time the twins, seeing how long they can keep
their hand in the ice, I've got Noah and Harris here,
and Helen Earwaker, who is a fingerprint researcher.
And, so, Helen, you're going to be looking at the twins'
fingerprints and seeing just how similar and different
they really are. Yes, I am indeed.
I'm going to take prints from both of them. Shall we start
with one of them, then? Fantastic.
Are you Noah or Harris? I'm Noah. You're Noah, OK.
OK. So, we're going to take Noah's right thumb,
and we're going to very carefully move the thumb round,
all the way from one end of the fingernail, all the way
to the other... Getting lots of ink on it. ..getting ink on
all of the ridges of Noah's thumb.
And then we're going to create a record of that thumb
by popping it down on the paper and rolling...
..all the way across.
Look at that - that's a beautiful thumbprint! Excellent. And up.
Perfect. Helen, I'll leave you to do the same with Harris... Thank you.
..and I'll move over here, because we've got Omar Mahroo, who's
an eye doctor, and we've got another pair of twins, Rosanna and Caitlin.
Who's Rosanna? Hi. You must be Caitlin.
And Omar is going to have a look at your irises.
So, Rosanna, if you'd like to sit down there.
We're going to have a look at the fine structure
of these twins' eyes. Are you comfortable there?
And, Omar, what are you doing there?
So, this allows us to take a detailed picture of the iris
of Rosanna's left eye. And what are you interested in? Are you
interested in the colour or the structure? No, actually, the fine
details of the structure, which you can't normally see with the naked
eye, but with a camera like this, you can. Lovely.
Oh! The ice has stopped.
Yes, well, actually, I didn't want to let them go
past two minutes and they both got that far, so they did the maximum
amount of time. Wow, that's amazing! Oh, my goodness, they're very
strong! You can take your ear defenders off. APPLAUSE
I wonder if...
Was it really not uncomfortable before then?
Did you just keep going, even though? Yeah.
You did! Oh, you're so bad, but it's...
Yeah, they're both very strong,
obviously, and they're both the same as each other.
Between twins, we'll see this pain resistance
is quite similar between twins, but very strong.
And possibly very competitive as well. Possibly quite competitive! LAUGHTER
Now, Helen, what about Noah and Harris and their thumbprints?
They're beautiful thumbprints. They are indeed. We managed some
excellent prints here from both of them. So, if we start by looking
at Noah's prints.
We're going to start by looking at first-level detail,
which is the type of overall pattern that we can see.
So, the question is are they broadly similar, then?
So, we would expect to see a level of similarity due to some
of the genetic ways in which those fingerprints have formed,
but also we'll expect to see some differences due to the exact
conditions in which that friction ridge skin, those fingerprints,
are formed within different areas of the womb. OK, so what can you see?
So, we can see here in Noah's print that we have lines
coming up and going around. Yeah, there's a loop.
There is a loop, indeed.
And we look at Harris's print and we can see, similarly,
a loop coming up and around.
But, if we look carefully, we can also see another loop
that heads back up. Indeed. Yeah.
So, Harris has something that we would call a twin loop.
And Noah doesn't have that? No.
Noah has what we would call an ulnar loop coming around here.
Yeah, just a single loop. That's fascinating. I mean,
it's very interesting, isn't it, that you've got similar fingerprints
but you're both individuals, you've both got something special
and different and unique about your fingerprints.
Brilliant. Thank you, Helen.
How are you doing over here, Omar, with Rosanna and Caitlin?
How do their eyes look? We've got some very nice pictures
of the iris of Rosanna and Caitlin here.
And, here, you can see, superficially,
they do look very similar, similar colours,
but, if you look at the fine detail,
you can see that Caitlin has a couple of small depressions,
we call them crypts, that Rosanna doesn't have in the same place,
and that's highlighted here.
What's really interesting is that when you look at their irises
like that, I mean, they are strikingly similar in terms of
colour. Yes, absolutely. Yeah, yeah, but it's the structure,
it's the fine structure that is actually different.
Yes, and then another difference is this ridge.
It's a raised area we call the collarette, and I've just
highlighted them in both twins and you can see the shape's subtly
different, and, if you superimpose them again,
they're not identical at all. Yeah. They're quite different.
Isn't that interesting, that when we really get into this level
of detail, again, you are each unique?
Thank you very much, twins. Thank you, Omar. Thank you, Helen.
APPLAUSE
So, Ronnie and Ritchie have stayed around, because last week
they did something else for us, and that was this.
So, what they're doing there is they're taking a sample
from inside their mouth, but it's not a sample of their own DNA,
it's a sample of things that are living in and on all of us.
We all have bacteria that are growing on our skin
and inside our mouth and our intestines,
and Ronnie and Ritchie very kindly agreed to give a sample
so that we could have a look at it. And here to talk to us
about that is Arwyn from the University of Aberystwyth.
Arwyn Edwards.
It's lovely to see you.
Thank you for doing this. So, you have here something
that has grown from inside their mouths.
Yes, so we have the bacteria from Ronnie and Ritchie's mouths
that have been plated out on a nutrient media,
so this nice nutrient jelly that is basically bacteria food.
But you can see some differences between them.
Which one of you is Ronnie? Him.
OK, Ronnie, just give you your bacteria back for a second,
so, you can see some differences there,
but it's all kind of little spots of this and that, so it's a bit
difficult to tell, and that's because only 1% of bacteria will
grow on agar. So, to really get in touch with our microbiomes,
what we have to do is do DNA sequencing.
So, this is really a small sample of what Ronnie and Ritchie
are carrying around, and all of us are carrying around?
Everyone's carrying around, right now. Everybody in this room.
So, how do you, then, sample the rest of the diversity?
Well, that's a good question. So, as well as collecting
those swabs, what happens was the samples of spit
then had their DNA in that sample extracted and we amplified bacterial
genes in there to do a sort of DNA fingerprint of the microbes present.
OK. So you have something here.
Ronnie, Ritchie, come over here beside me and have a look.
So, now you're loading the sample in.
I'm just preparing for the sample to just go in. OK, that's...
This is the sample going in here, this kind of milky liquid here. OK.
And how long does it take before this sequencer starts actually
generating some sequence? It's already started.
It's already started? Yeah. Wonderful!
That's incredible. So we've gone from the dark green colours here,
with nothing going through the machine, and now we've got
the light green colour and you can see numbers here flashing up,
saying that it's sequencing. But this is going to take a while.
I don't think we can wait for this to finish. No, so here's one we
made earlier. Yes. So, it takes...
It's very fast, but it still takes a few hours.
So, we did the DNA sequencing earlier and we sequenced 2 million
DNA molecules from both of you put together. Wow!
And, from that, we have numbers of types of species
that we have there from bacteria growing in your mouths.
You're twins, obviously, so you have more in common
than you have apart, so 116 species of bacteria growing in
your mouth right now that you both have and you're both sharing,
but, then, Ronnie, you've got 18 species that are unique to you and
your twin brother doesn't have those species, and, then, Ritchie, you've
got slightly more - you've got 25 species that are unique to you.
So, even though your genomes are identical and your daily habits
are very, very similar, you have some bacteria
that make you unique. Yeah.
And, so, these are totally separate from the genome we've been
talking about until now, so it's not your genome, it's the genome
of little things living on your skin and in your mouth. Yeah.
So, if somebody had a pet, would that influence what's growing?
Yes, so, if you have a pet dog at home, you are likely to share
many, many bacterial species between you and your dog,
so, next time you have dogs in the audience here,
give them a good pat, because you're picking up friendly bacteria.
So, would somebody be more like their twin or more like their pet?
That's a good question. Depends on how much you like your twin brother. LAUGHTER
OK, well, thank you so much, Arwyn, and thank you so much, Ronnie
and Ritchie. You can keep those,
and you've been wonderful volunteers. Thank you.
Aoife, that was incredible.
I mean, I think that, you know, it's interesting to see how many
different species of bacteria we've got living in our mouths,
but also the fact that the sequencing is so quick
and so miniaturised now, that amazing technology.
It's incredible, yeah.
So, I want to test you a bit now... Oh, yeah? ..because we've been
talking about various characteristics
that we can map on to our genetics,
but if you didn't know what somebody looked like and you didn't know
who somebody was, how much could you tell about them
if you had their DNA sequence? Yeah. So, now you're talking about
basically the Holy Grail of genetics.
Can you take a DNA sequence and describe the person?
Well, it's quite hard because we've already talked about examples
where you might have particular genes,
and it gives you a chance of being one thing or another,
but it doesn't totally fix the outcome, and then there's
another side to it is there's lots of stuff
that we just don't know yet.
There's lots of examples where we just don't know how exactly
the genes work, but... So, I've got somebody's DNA results here.
Yes, yes. So, we have a mystery guest, and, honestly,
I don't know who this guest is, nor does Alice, but I have been
looking at some of their DNA.
So, this mystery guest is going to come in, and don't say
anything that might let us guess who it is, because we have no idea
who this is and we are going to make some predictions of some
of this person's traits, just based on the DNA sequence analysis.
So, please come in, mystery guest!
OK, mystery guest, you don't have to say anything to me,
because I don't even want to hear your voice,
but thank you very much for coming.
So, the mystery guest over there has two bells,
and they can use one of them for yes and one of them for no,
so the first thing that I'm going to talk about with regards
to this guest is that this person has two X chromosomes.
These are the sex chromosomes.
So, usually, when somebody has two X chromosomes
then they're female. It's not 100% but it's most of the time,
so I'm going to go for that we have a female guest.
Am I correct? BELL RINGS
Yes. Ah. OK, one right, OK. You're doing well, Aoife. Thank you. THEY LAUGH
Now, let's see.
So, we also know that skin colour is highly genetic,
but we don't know all the variants very well,
so, based on the genetic variants, I'm relatively confident
so, a brown to dark brown. Am I correct?
BELL RINGS
OK, good! Yes, OK. I wasn't certain about that one.
Perhaps you might have detached ear lobes. So we have ear lobes
that can be... My ear lobes are detached and Alice's are attached.
Mine are attached, yeah. So, do you have detached ear lobes? Yes?
BELL RINGS Oh, great.
So, we talked earlier about lactose tolerance as well, and, so,
this person does not carry the variant
that we normally see in European individuals
that allows them to drink milk.
I'll go for that this person is lactose intolerant.
BELL RINGS OK. There we go.
So, some people, you know the herb, coriander?
The green herb, coriander?
So, for me, that tastes really nice, but for about 13% of people
it tastes like soap, and this person might be one of them.
I'm not confident, but I'll say for soapy coriander, yes?
HORN HONKS Oh, OK. There we go.
Interesting. So, finally, this one I'm quite confident that
this person has either dark brown or hazel eyes.
BELL RINGS OK, all right.
Well, that's as much as I'm going to do, but...
But what's interesting about this is you know some of those traits
are better predictors than others, but it's never going to be 100%.
So, you might be right, sort of, you know, seven, eight, nine times
out of ten, but there's some people that you're not going to guess right
by knowing their genetics. No.
OK, I think we just need to end the suspense and see who actually
is our mystery guest. Do you think we should reveal it?
I think we should reveal our mystery guest. Let's see. ALICE GASPS
Hello! Oh! Ruby! How are you? APPLAUSE
Thank you very much. Thank you so much for coming.
Quite a surprise.
Were you impressed that Aoife managed to guess so much about you?
Yeah, and I felt so bad that I love coriander.
You love coriander? I love coriander.
But your genes say that you should taste the soapy taste.
That's not right, then. Tastes delicious to me.
So that one didn't work. Oh, that's amazing. Ruby, Star Baker.
Thank you very much. Aww, thank you for having me. Thank you.
So, this is fascinating.
We do seem to be able to make some reasonably good predictions
about people based on their genetics,
but that was a... that was a bit of fun.
It was a lot of fun, and I got a cupcake,
but there is a more serious side to this, too, because we can
use genetics to predict our risk of
disease, and we need to think really carefully about how we do
that and whether we want to know this information. So, to help us
think through some of these issues,
I would like you to welcome my friend, bioethicist,
Professor Heather Widdows. Heather.
Hello. APPLAUSE
Now, Heather, first of all, what is a bioethicist?
Well, my job is to think not about what we can do,
but about what we should do, so I think about the implications
for all the stuff you've heard.
And, now that we can predict risk of some diseases,
some better than others, what are the advantages to knowing
that kind of information?
Well, some of it is disease-specific,
so if there's a treatment, for instance,
then you need to know, but there are general things
that people think that maybe you have a right to know,
that you should know, and that will help you plan your future.
So, that could be things like lifestyle choices.
So, if you have a disposition, say, to something like a form of cancer,
then you might want to plan your life a bit differently.
So, when you're thinking about things like when you want
to have children, if you want to have children,
you might want to have children earlier, you might maybe
want to do your bucket list, you don't want to wait
until you're retired to go and, you know, climb Mount Everest.
Yeah, so it can kind of help with planning. Right.
You could change your lifestyle and hopefully lessen your risk then.
But what are the negatives when it comes to knowing your disease risk?
So, just like some people think you should know,
other people feel very strongly the other way.
They think that you should have an open future,
that knowing is going to make you think that you're ill,
when in fact you're very well still. So, even though you're not ill,
you might start behaving as if you are,
and you kind of wish your life away. So, for very many other people,
they think that, in fact, we really have a duty or a right not
to know that's important.
So, we'd like to explore some of these areas
with you, and, at your feet, you've got voting cards.
So, when we ask you to vote, what I'd like you to do
is hold up your answer with the answer facing us.
So we're going to talk about a number of diseases and see
what you think, see how you feel about it. Have a good think about
whether you'd really want to know if you had a higher risk
of developing such a disease.
So, shall we have a think about early onset Alzheimer's disease?
Yes, so Alzheimer's is one form of dementia, and usually the tests
will only tell your susceptibility and risk, and it's more about
a cluster of the gene's environment.
So, this is something which would cause memory loss,
eventually makes it difficult for you to be independent
and to look after yourself.
At the moment, there is no treatment for it,
so, would you like to know if you had a higher risk
of developing early Alzheimer's?
I think there is a majority of yeses, actually,
but there's quite a lot of people who wouldn't like to know.
So, let's think about another disease.
OK, so the next one we want to think about it is type 2 diabetes.
So, this is where your body responds to sugar.
It can affect your eyesight,
and it can gradually get more severe.
It's a disease where you can manage it very well by lifestyle changes.
So, obesity is a key factor in the disease, so, knowing means
that you really can change your lifestyle to address it.
So, who would like to know if they had a slightly higher risk
of developing type 2 diabetes?
That's really different. Even more. Yes.
So, the vast, vast majority of you are saying yes.
It's important to remember with these kind of ethics questions,
there is no right or wrong answer, it's what's right and wrong for you.
So, let's think about one final disease, then.
Let's think about cancer.
Now, there are lots of different types of cancer -
some of them are treatable, some of them are more difficult to treat -
but if you could test for a higher risk of a particular cancer
where there was a treatment option,
what would you feel about that?
Would you...would you want to know if you were going to develop
this particular type of cancer?
I think it's about two thirds yes and about a third no? Yes.
I think that looks...
Now, our roving reporter, Aoife, is going to come and ask you
some of your opinions about this and why you voted in various ways.
Is there anybody who'd like to tell me what they voted
and why they voted? So, I'll come around to you. Oh, sorry.
I'll fall on the stairs as well. What way did you vote
on the Alzheimer's one, and...? I voted no.
And why did you vote no?
I think you shouldn't live knowing, like, in fear.
You should, like, make your own choices. Yeah, very interesting.
Anybody else who wants to tell me about one of their answers? Yeah?
But what, which one...? I voted yes on Alzheimer's.
Yes? Because I think it would be nice to warn your family... OK,
very interesting. ..and, like, share things.
Yeah, yeah. Let's see if there's somebody up here.
You voted no. OK, do you want to tell us, what did you vote no to
and why? I voted no to the first one because... Alzheimer's? Yes,
because I didn't want to know, because then it would make me feel
scared, and then I won't enjoy my life as much as I would have.
Very... I mean, it's very sophisticated opinions coming from
our audience here, so give yourselves a round of applause.
Thank you very much for doing that with us. There was some
really, really thoughtful answers there, I thought, Heather.
Absolutely. Lots of the answers you came up with are exactly
the answers that ethicists talk about, so...
One really interesting thing, of course, about DNA
is that it connects us with other people.
So, this is something you've thought about long
and hard, Heather, that, in fact, when you have your DNA sequenced,
it's not just your genes that you're looking at.
Yeah, absolutely. The two key things that make genetic information
so different are that it's shared and it is identifying,
so, it's shared with other members of your family,
and we don't really know how to balance that.
So, if we think about something like, you know, testing for
the indicators for breast cancer,
if you're 15 and you want to be tested, and your mother is 35,
40, and doesn't want to know, and you know that there's
kind of cancer in the family, if you go and get tested and turn out to be
positive, then you will have information about your mother
that she does not want, and we need to think about
how we ethically manage that.
It feels like we're only just catching up with the ethics
of this whole area of biology.
It feels like we're not really kind of grasping how to deal
with that information quite yet. Yeah, no, I don't think we are
at all. I think that's exactly right. You know, the science has
moved on quite dramatically. This is all about unknowns
in the future. Who will want your information?
Will it change what you can do, employment wise?
Will insurers want it?
And, of course, there is one particular area when a genetic test
is carried out, it's actually not on your own DNA but very much
on the DNA of another individual, and that's when we test babies
in the womb when we do antenatal testing, and we're able to test
for more and more things now, but, again, some really difficult
decision-making when parents are presented with results.
Absolutely. So, you know, perhaps the one that's most well-known is
the test for Down syndrome. That happens very routinely,
so, that means that nearly every pregnant woman in the UK will have
that test and they will be offered it routinely, and they may
just think, "Oh, well, this is just part of getting ready
"to have the baby," and what they may not realise is that,
once that result comes back, if that's a positive result,
then the only thing to do is either continue,
so the test can help you prepare, or you can end the pregnancy.
And that may be something that they hadn't quite realised was happening.
So, very difficult decisions.
I want to introduce you to somebody who did
have an antenatal test for Down syndrome, and her daughter,
so, please will you welcome Donna and Frankie.
APPLAUSE
Oh, she gave us a lovely wave.
She's excited to be here.
So, Donna, you had an antenatal test, so you knew that Frankie
was going to be born with Down syndrome.
We had a blood test and she came back as a high chance
of having Down syndrome.
We didn't know until she was born that she had Down syndrome,
but we knew there was a high chance of it.
Yeah. And did it...did it help you prepare?
Yeah, definitely.
I mean, I think I went through my pregnancy, in my head,
thinking, "Baby has Down syndrome."
It wasn't anything that was negative for me.
I was quite happy and quite excited about my first baby. Yeah.
It didn't matter how she came out - she was Frankie.
Yeah. Aren't you?
And she's...and she's different, but she's lovely.
She's yeah, you know, no child is the same.
She is so unique in so many ways... Yeah. ..but I wouldn't change
a thing about her. She's perfect.
Yeah, and we're all unique. Exactly.
Thank you very much. Donna, Frankie and Heather.
APPLAUSE
So, Aoife, we've been looking at
what we can do with this new technology.
It is new, and it's getting faster and faster and cheaper and cheaper
and we can read DNA and we can make some predictions
about what we're going to be.
But we can actually change DNA now as well. Yeah.
And we have a really wonderful example of this,
so, if you could please welcome a leader in this field of gene therapy
from Great Ormond Street Hospital, Professor Bobby Gaspar.
APPLAUSE
Thank you so much for coming here. Please sit down.
So, you've been working in the area of gene therapy,
so, being able to change genes to help patients
for quite a number of years now.
Yes, well, I actually started right at the beginning
when I was a junior doctor at Great Ormond Street Hospital,
about 25 years ago. Wow.
And, really, what we're trying to do is, in some diseases,
it comes about because a gene is defective or missing.
And what we want to try and do is put a working copy of the gene
back into those cells, so they now have the correct gene,
the gene works, it makes the right signals
to be able to correct that disease.
So, it's a very fundamental way of correcting diseases.
So, you're really getting to the root cause.
And you helped the first-ever patient
to be helped with a gene therapy. The first worldwide.
And he's the first successfully treated child by gene therapy
in our team at University College,
and Great Ormond Street helped treat him back in 2001.
And he's here this evening to come and show off
how strong and healthy is. Please welcome Rhys.
APPLAUSE
Hello, Rhys. I must say, you are looking very healthy.
We have a picture of you from about one-year-old, I think, up there.
What you can just about see there is a plastic bubble around Rhys.
So, you spent a lot of time in that bubble.
When I was born, I had to be put into this bubble
because I wasn't born with an immune system
and, so, any sort of bacteria or viruses in the atmosphere
that I would inhale or breathe in,
it would then harm me because my system wasn't very strong at all.
And Professor Bobby Gaspar was your doctor? Yes.
So, what did you do for Rhys?
Well, Rhys, as he says, there was a single gene that was missing
in his bone marrow, not working properly.
He couldn't make immune cells.
And, so, my colleague and myself, we were working on a new way
of treating this condition through gene therapy
and that meant taking Rhys' own cells.
So, he went to the operating theatre
and we took out your bone marrow stem cell
and we put, in the lab, we put a working copy of that gene,
the gene that was missing, we put the working copy of that
back into his bone marrow cells
and then gave those gene-modified cells back to Rhys.
And, then, over a few months, his immune system started to grow
and this was the first time we'd seen it in any child in the UK.
And, then, after about six months,
it was growing and working really well.
So, we were really, really delighted how well it worked.
Wow. And, so, Rhys, this has totally changed your life. Yep.
No, I don't think I'd be alive, honestly.
It's such a wonderful example of how genetics
can transform medicine and we can have these new therapies.
Now that we're able to identify all of these different genes
that cause diseases,
now we'll see genetic treatments for eye diseases,
certain leukaemias can be treated by genetic therapies
and there'll be other conditions as well
that will be treated by gene therapy.
It's such a positive story.
So, thank you so much, Rhys and Bobby, for coming in and telling us.
Thank you. Thank you.
APPLAUSE
Rhys' story was just amazing.
And this does feel like a new frontier in medicine,
being able to fix faulty genes.
And I wonder how far we go with this
because fixing disease seems like a very positive thing to do,
but you could make other changes.
I mean, parents could be choosing, I don't know,
eye colour, skin colour of their babies
and that, I think, is a very, very different issue.
Definitely. I have a personal view on that
and that is that it shouldn't be done.
I don't think it's a suitable use of the technology
and it's something that should be avoided.
And this science and this technology is moving really fast,
so, all of you will have to think about this really carefully
over the course of your lives.
Science is fantastic.
It tells us so much about the world around us and about ourselves,
and it provides us with amazing technological tools.
But we have to work out how we're going to use those tools
and that's not just a question for scientists and ethicists,
it is a question for everybody
because this science and this technology belongs to all of us.
Yeah. And just because we can do something
doesn't mean that we should.
But one thing that we do see in all of this is that
each of us is a total one-off, even the twins.
We're a unique parcel of talents, strengths,
weaknesses, foibles and chance.
We started out wondering who we were, what makes us unique,
what makes you, you,
and we found an answer to that.
That it's your past,
it's all your ancestors who passed down their genes to you.
But it's also your own past, what happened to you in the womb
and what's happened to you since you've been born,
combined with a lot of chance as well,
makes each one of you a unique individual.
And there is no such thing as a perfect human,
there is no normal human.
Humanity is all of us.
Each one of you is different
and each one of you has something special to give.
Now, to finish off,
we have been working with people from all over the country,
from lots and lots of different schools,
and we've got a special treat.
This is the B Positive Choir
who want you all to stand up
and join in, as we finish the Christmas lectures
with a celebration of difference and diversity.
PIANO INTRODUCTION
# I'm not a stranger to the dark
# Hide away, they say
# Cos we don't want your broken parts
# But I won't let them break me down to dust
# I know that there's a place for us
# For we are glorious
# When the sharpest words wanna cut me down
# Cut me down
# I'm gonna send a flood, gonna drown them out
# Drown them out
# I am brave, I am bruised I am who I'm meant to be
# This is me Look out, cos here I come
# Here I come
# And I'm marching on to the beat I drum
# The beat I drum
# I'm not scared to be seen I make no apologies
# Oh-oh-oh-oh Oh-oh-oh-oh
# Oh-oh-oh! # Oh-oh-oh!
# Oh-oh-oh, oh, oh
# We are bursting through the barricades
# Reaching for the sun
# We are warriors
# Yes, that's what we've become That's what we've become
# I won't let them break me down to dust
# I know that there's a place for us
# For we are glorious
# When the sharpest words wanna cut me down
# I'm gonna send a flood, gonna drown them out
# This is brave, this is bruised
# I am who I'm meant to be This is me
# Look out cos here I come
# And I'm marching on to the beat I drum
# Marching on to the beat I drum
# I'm not scared to be seen I make no apologies
# This is me! #
APPLAUSE AND CHEERING