[MUSIC PLAYING]
[APPLAUSE]
ROBERT PLOMIN: So
thank you, [? Jan, ?]
and thank you all for
coming on your lunch hour.
It's great to talk
to a group like this.
I usually talk to academic
groups or people in education,
so I'll be curious to see
what you make of all of this.
But I've been
informed I'm not here
to tell you things that
are relevant to what
you do at Google.
It's more about general interest
in genetics and behavior.
When I started in graduate
school in the early '70s,
you might find it
hard to believe,
but it was dangerous to
even talk about genetics.
Psychology was so dominated
by environmentalism--
the view that you
are what you learn--
that it was dangerous
professionally and sometimes
personally even to
mention genetics.
The textbooks at the time--
this is the 1970s--
would tell you
if you look up schizophrenia,
it would tell you
that schizophrenia
is caused by what
your mother did to you in the
first three years of life.
And since then, a
mountain of evidence
has convinced most scientists
that genetics is a major factor
in most aspects of behavior.
And today, I'd like to just
because I want to leave time
for questions,
I'm going to focus
on one aspect of behavior,
school achievement,
in part because this is a talk
I gave at New Scientist Live
on Saturday.
So what do you think is
responsible for how well you
did at school?
So it's easy to think about
tangible environmental factors
like your parents, your
teachers, your schools,
but what I'd like
to convince you
is that something
intangible, DNA, is
the major factor responsible
for differences between children
in their performance at school.
The environment is important
too, but the way it works
is very different from the way
we thought it worked before we
took genetics into account.
Previous studies of the
environment are confounded
because things that run in
families could run in families
for reasons of
nature-- genetics--
as well as nurture.
But if you ignore the nature
and assume everything's nurture,
you make some very
wrong conclusions
about the environmental
influences on behavior.
And this is all a lot more
relevant and important now
with the DNA revolution.
So I think that'll probably
interest you even more.
And I'll try and get through the
first part of my talk quickly
in order to spend more
time on the DNA revolution.
So this is my book, "Blueprint."
I'm very sorry that Penguin
didn't get it here in time,
but I bet you it'll come right
after my talk [INAUDIBLE]..
But Penguin is usually
very good at these things.
The first half of the
book is about genetics.
Basically, how do we know
genetics is so important?
And what have we learned
about the environment
by studying it in
genetically-sensitive designs,
and then also some of
the implications of it.
And as I say, instead
of psychopathology,
like psychiatric
disorders or personality,
I'm going to just focus on
one aspect of this huge area,
school achievement.
Then the second part of
the talk and the book
is about the DNA
revolution-- identifying
specific DNA
differences that account
for differences in behavior.
And that's what's going
to change everything.
So I think it's very important.
It's the reason I
wrote the book now
is to say we really have to
discuss some of these things
because they're happening now.
So just to make sure
we're on the same page,
you know, genetics,
heritability-- these
are difficult concepts
for people to grasp.
But when you ask people,
how heritable is eye color--
that is how much is it due to
inherited DNA differences--
I've done these surveys
and people, on average,
would say it's
about 90% heritable.
That means it's almost
entirely due to inherited DNA
differences.
But when you turn
to complex traits
like weight, how heritable
do you think weight is?
And if you do
population surveys,
probably not of groups as
smart as this one, but people
would say about 20%, 30%.
They think there might be
some genetic influence,
but it's mostly environmental.
But in fact, it's 70% heritable
across a wide range of studies,
including DNA studies.
And that's really important
because it means that
the differences between
people in this room--
you all seem to be
skinny, except for me--
the differences are substantial,
but the major factor
is inherited DNA
differences, which
is really important in our
society with fat blaming
and, you know, fat shaming, the
sorts of stuff that goes on.
We need to recognize
people like me
find it a lot easier to put on
weight than you skinny people
and a lot harder to lose weight.
So when you turn to
school achievement though,
people underestimate
genetic influence even more.
They think it's about
maybe a little bit
of genetic influence,
but not much
because achievement means--
the etymology of it is--
by dint of effort.
As opposed to ability, which
people say, oh, that's genetic.
But in fact, school
achievement--
tested school achievement-- in
English in schools in England
is about 60% heritable,
meaning 60% of the differences
between kids in their
tested school achievement
is due to inherited
DNA differences.
And you can see
how important it is
to know that because we tend to
assume it's all environmental.
It's all due to
how good a school
you went to, how much your
parents push you on this,
but parents don't have
nearly as much control
as they think they do.
So that's one of the
messages I want to get to.
The most misunderstood
concept in genetics
is heritability--
these six syllables.
And so it's important
just to spend
a minute talking about it.
We're only talking about
what makes people different--
why some of us are heavier
than others, why some of us
do better at school than others.
Of our three billion
base pairs of DNA
in the double helix of DNA,
more than 99% of those DNA bases
are the same for
everybody, but 1% differs.
And the 99% is what makes
us human, but the 1%
is what makes us
different genetically.
So what we're asking
is to what extent
does the 1% of DNA that
differs between us make us
different in traits
like school achievement?
We're only talking
about describing what is
rather than what could be.
So we study like twins,
and adoptees, and DNA
in a representative
English sample,
but that only tells
us about what is now.
Say in terms of weight,
given our genetic differences
and our environmental
differences now,
how much do genetic
differences make a difference?
If you change the
environment, if you
study a different population
in a different time,
that would change.
But that's a good
descriptive statistic
that is sensitive to the
environment in which you
study it.
And we're only describing the
normal range of variation.
I mean, sure, it's
an issue you all face
that you can only talk about--
you can't generalize beyond the
sample that you've described.
So these samples
that we study may
be representative of
95% of the population,
but they don't
include, say, families
where parents are abusing the
kids because those people don't
participate in studies.
Nor does it include the
genetic extremes of single-gene
mutations that are very
severe and debilitating,
but they're very, very rare--
1 in 100,000, 1 in 200,000.
So if you have a sample of a
few tens of thousands of people,
you don't have
those in the sample.
And lastly, I want to
emphasize we're talking
about genetic influences.
These are nudges,
probabilistic propensities.
They're not innate,
they're not immutable,
and they're not deterministic.
So I have to whip through
this, but those are really
important points.
And you scratch
the surface of what
people know about
genetics, and they somehow
think you're talking about
innate, immutable influences,
which is the case for
single-gene disorders, which
is how most of us learn
about genetics from Mendel.
There are thousands of
single-gene disorders.
As I say, they're very rare.
But if you have the
gene on chromosome 4--
the form of a gene
called an allele--
for Huntington's disease, you
will die from Huntington's.
It's hardwired, deterministic.
It doesn't matter what
your environment is
or anything else.
The problem is when we talk
about complex traits, not just
psychological traits, but
most of the medical burden
in society is caused
by common disorders.
And they're not caused
by single genes.
They're influenced
genetically, but by many,
many genes' small effect.
That makes them probabilistic
rather than deterministic.
And that's a really difficult
jump for people to make.
So one of the methods
we used for 100 years
to study the extent to which
genetic influence is important
is a sort of
biological experiment
where there are
two types of twins.
I'm sure you all know.
1% of all births are twins.
1/3 of those are identical
twins called monozygotic.
It's a single zygote--
that is a fertilized egg--
that for reasons unknown in
the first few days of life
divides in two.
And those are clones
of one another.
They're genetically identical
if you sequence their DNA.
So they're 100%
alike genetically.
The rest of the twins are
like any brother and sister
who happened to be
born at the same time
because their mother had two
eggs in the womb at the time
and were fertilized.
So they share 50%
of their genes.
They're 50% similar.
So you'd predict that any
traits, say school achievement,
that is influenced
genetically, you'd
have to predict identical
twins will be more
similar than fraternal twins.
And you can use the
extent to which that's
true to estimate heritability.
And so when I came
to England in 1994,
I began the Twins Early
Development Study,
which is the world's largest
study of development of twins.
We started with about
15,000 pairs of twins.
And we studied them 14 times
through young adulthood, most
recently at 22 years of age.
And about 10,000 pairs
continue to participate.
Importantly, as
I'll mention later,
we also have DNA on them.
So they led the way in terms
of some of the DNA analysis
I talk about.
I was interested
in studying things
that hadn't been studied
much before, like language
development in the early
child years or behavior
problems which developed
very early on and are highly
heritable in early childhood,
like attention deficit
problems.
But when they got
to school because I
was interested in
cognitive development,
I really wanted to study
kind of the business
end of cognitive ability
and that school achievement.
So this summarizes 15 years
of work in the Twins Early
Development Study.
These are the
heritability estimates
based on identical and
non-identical twin correlations
across all the key stages,
which key stage one at 7
going to 9 to 12.
16 is GCSE.
18 is A Levels.
And you can see that
the average heritability
exceeds 60% at all ages,
including the very first grade.
A lot of people would have
expected that in first grade,
your performance is
more a function of what
your parents did, but it's
actually just as much genetic
as A Levels or GCSE.
And in the behavioral sciences,
explaining 5% of the variance
is a very big deal.
Explaining 60% of
the variance, meaning
differences between
people, is off the scale.
So it's a huge effect.
And oops.
My N got misplaced.
It's not just the
twin method, there's
many other methods
that are used.
If the twin method is like
a biological experiment,
the adoption method is
like a social experiment.
So family members share genes,
as well as environment-- nature
and nurture.
We've known forever,
everything runs in families.
Parents who do
well at school have
kids who do well at school.
For decades, people
have said, no problem.
That's just nurture.
Those parents provide a better
environment for their kids.
But when you start
thinking about genetics,
you say, well, but they
share 50% of their genes.
Could it be nature,
not just nurture?
The adoption design
separates that
by studying parents
who are related
genetically to their kids--
these are birth parents
who relinquish their kids
for adoption at birth, so they
share nature, but not nurture--
and then adoptive parents
who adopt those kids
early in life and share
nurture, but not nature.
So the book also
describes a study
I've done for 40 years
called the Colorado Adoption
Project, which is about 250
families-- adoptive families--
where we had data on the birth
parents, the adoptive parents,
and the adopted
kids longitudinally
through adulthood from
infancy to adulthood.
And this summarizes
20 years of research.
We also had matched
non-adoptive families
who share genes and
environment with their kids.
So general learning
ability, which we call
g to avoid the word
intelligence, which is just
like a red flag to
a bull for people,
but there is this construct of
general cognitive ability which
is one of the better
measured traits.
So just don't have a
knee-jerk reaction against it.
But what's been known for a
long time is it runs in families
and that parents
and their children
increasingly resemble each
other as the kids grow up.
So that shows you the
parent-offspring correlation
when parents share genes and
environment with their kids
goes up to about 0.3-ish
by late adolescence.
So is it nature or nurture?
For a very long time, it
was assumed to be nurture.
And it's not an
unreasonable hypothesis.
But if it's nurture, that
is the parents are giving
the kids the environment they
need to develop cognitively,
you'd have to predict that
the adoptive parents ought
to be just about as similar
to their adopted kids.
And the correlations
are actually zero.
So that suggests it's
not nurture in the sense
that we've thought about
it as systematic effects
of the parents, say.
Well, then is it really nature?
Could it really be that
these birth parents who
don't share environment,
but share genes
are correlated as much as
parents who rear the kids?
And the answer is yes.
So it's a powerful demonstration
of the importance of nature
and the unimportance
of nurture as we've
defined it in terms
of systematic effects
of the family environment.
The environment is important
because heritability is not
100%.
It's more like 50% on average,
but it's a very different sort
of environment than
anyone ever thought about
from Freud onwards.
So the first part of the book--
and I'm whipping
to the conclusions
here because I want to get
onto the molecular genetics--
it talks about how do we
know genetics is important
and just how important are they.
But then some of the
most important findings
are about the environment
when you control for genetics.
So the second big
finding is this one
I just alluded to that the
environmental effects are
important, but
they're not nature
in the sense of systematic
effects of the environment.
Adoptive children-- a
third of adoptive families
adopt a second child,
and they're genetically
unrelated to each other.
They correlate zero.
Whereas siblings who grow
up together and share genes,
they correlate substantially--
0.2 for personality and 0.3
for, say, cognitive development.
So for 30 years,
people have been
trying to find out what are
these mysterious factors that
make two kids in a family
different from one another?
And it could be lots of things--
accidents, or illnesses,
or different peers, or
the parents treating them
differently-- but after
30 years of research,
no systematic factors
have been found.
And so I've come
to the conclusion,
called the dark hypothesis,
that the effects
are essentially idiosyncratic,
stochastic, random,
in a word, chance.
So they're unsystematic.
It could be like Bill
Clinton in his biography,
he talks about why did
he go into politics.
And he says, it's because
at 16, he shook JFK's hand.
See, that would be a
good example of this.
I mean, that's not a
systematic variable
you could measure very well.
And maybe, you know,
knowing Bill's history here,
you can't bet a lot on
its veracity, I suppose.
But that's the sort
of thing you get--
these idiosyncratic experiences.
Like why are you doing
what you're doing?
I know in my case, it's all
these chance sorts of events,
just little nudges
in one direction
or another that snowball.
So that's what we
think it's about.
And the other third
finding is what we--
that's what we call
non-shared environment.
It's not environment
shared by kids growing up
in the same family, going
to the same schools.
The third finding is called
the nature of nurture.
It's the idea that what
looks like systematic effects
of the environment are
actually mediated genetically.
So you know, correlations
don't imply causation, right?
Everyone knows that.
But if you see a correlation,
like I do once a week
in the papers, parents do this
and the kids are like that.
So parents who read
out loud to kids
have kids who read better
when they go to school.
It's so hard to resist an
environmental interpretation,
but correlations
don't imply causation.
And if you start saying,
what about genetics,
it'll drive you mad
because, you know,
they share 50% of their genes.
It could just be
parents who read
have kids who read,
but more increasingly,
it's sort of the
nature of nurture--
that the correlation goes in the
opposite direction from the way
we think it goes.
Parents are responding to
differences in their kids,
which I really see as a
grandparent with six kids.
One grandchild does what
I thought grandchildren
are supposed to do.
She'd let you read
to her all day long.
She loves words and reading.
But then the first one I
had, she didn't want to read.
She wanted to kick
a ball around.
She wanted to be active.
It almost would
have been abusive
if I said, no,
you're a grandchild.
I'm a grandparent.
You sit there and I read to you.
That's what you're
supposed to do.
But it doesn't.
You know, we're responding
to differences in the kids
and that's as it should be.
And also in education,
we should be recognizing
that kids differ, try to
minimize the weaknesses,
maximize the strengths,
which I'll try to get onto.
Oops.
So I know I went
through this quickly,
but if you look at these
three things together,
they lead to the title of
the book, which I agree
is provocative and misleading.
But what I'm trying
to say is that DNA
is the major systematic
force making us
who we are as individuals.
It's systematic in a sense.
I try to emphasize that because
the environment's important,
but it's not systematic.
And so what I'm saying
to tie these together
is if you were cloned and your
clone was reared, obviously,
in a different woman
prenatally, grew up
in a different family
with different parents,
went to a different school,
had different friends,
had a different job,
that clone would
be very similar to
who you are now,
not just in school
achievement, but in personality
and psychopathology.
In fact, that clone would be
as similar as identical twins
reared together.
So with school
achievement, they correlate
about 0.7, identical
twins reared together.
Being reared apart doesn't
make you any less similar.
So you can see
that that's talking
about the importance of
nature, the unimportance
of the systematic
family environment.
And it's not just a
hypothetical experiment.
I don't know if you
know who this is.
Nope?
Yeah.
You'll know in just a minute.
This is Bobby, who
grew up in Long Island
in a very wealthy family.
He went to university
in Upstate New York.
And on the first day,
everyone's calling Bobby, Eddie.
Girls are coming
up and giving him
a hug and a kiss saying, oh,
Eddie, it's so good to see you.
So he's thinking,
psychology experiment,
looking for the cameras.
But then he met Eddie.
And they quickly worked out
they had the same birth date.
They were adopted from the same
adoption agency in New York.
And the publicity
that came from that
led to the rare circumstance
of a third identical triplet
because I told you that
the zygote separates
for reasons unknown.
Sometimes, one of those
zygotes separates again.
So these are clones
of one another.
They have the same DNA sequence.
And the film-- this is
a documentary film that
won the Sundance
award last year called
"Three Identical Strangers,"
and it's available on streaming.
And I really recommend it
as a dramatic illustration
of the points I'm
trying to make,
but it is just an anecdote
and an illustration.
And just watch the first half.
The second half is
a very bad story
because did you think, why were
they separated and didn't know
about each other's existence?
Why was one put in
a lower-class home,
one in a middle-class home,
one in an upper-class home?
A nutty psychiatrist, who was
actually out to prove nurture
is important.
He thought it was going to
be a definitive experiment.
Identical triplets-- put one
in a lower-class family, one
in a middle-class family,
one in an upper-class family.
They already had adopted
another kid from the agency,
so they knew what the
parenting styles were like.
So they made them as
different as possible.
And he was a Freudian.
You know, this was in the '50s.
He just assumed the environment,
it's all about nurture.
But then when the results
started coming out,
he actually buried them.
So they're under lock and key at
Yale Medical School till 2066,
never been published.
But this film exposes it.
And there's probably
at least half a dozen,
if not more, identical
twins who have been
separated as a result of this.
He was a psychiatrist
to that adoption agency.
Right, so it is
just an anecdote,
but behind it is systematic
data on twins reared apart.
I did a study in Sweden
of over 100 pairs
of identical twins reared
apart, as well as other adoption
designs like biological parents
and their adopted-away kids,
adoptive siblings, biological
siblings adopted apart,
and increasingly DNA.
You can use DNA itself
in unrelated individuals
to estimate heritability,
but it would take too long
to explain that now, but it's
kind of the hot new thing.
So they all converge on the
conclusions that I mentioned.
So I would have been--
well, I'll just mention
implications of that research.
And the main thing to emphasize
is no necessary policy
implications.
This is an old-fashioned view
that policy depends on values,
as well as knowledge.
And I'm increasingly
cynical about this--
that better decisions are made
with knowledge than without.
More often, I think if your
data, your research agrees
with the values of the
government, they'll use it,
but it doesn't actually
inform the policy very much.
But here's the one thing that
got quite a bit of attention
in terms of schools.
If you see what I have
been talking about,
can you see how
this makes sense?
Schools matter, but they
don't make a difference.
So schools matter a lot.
Kids have to learn basic
skills of literacy,
and numeracy, and
enculturation, but they
don't make a difference.
Kids going to the same school
aren't any more similar
than if they had gone
to different schools.
And part of that is because
60% of the differences
are genetic anyway and the
environmental effects are not
systematic.
So one quick fact that's
important for you guys
because you look like you're
at risk of child-bearing age.
And you know how in England,
we have this crazy selective
system for secondary schools.
Parents spend hundreds
of thousands of pounds
to get their kid
into a better school.
A better school, why?
Mostly based on OFSTED
ratings of the schools.
People don't ask about the
effect size of the OFSTED
ratings.
So they cost about
10 grand each.
You know, they're really
good ratings of schools--
atmosphere, teacher support,
bullying, the whole schmear.
But then they are the primary
difference between schools
in the league tables.
So the question is how
much of the variance--
how much of the
differences between kids
and their GCSE scores is
accounted for by OFSTED ratings
of school quality?
So some kids go to schools where
they have very high ratings
and some go to schools where
there are very low ratings.
So heritability counts for 60%.
OFSTED ratings
account for 4%, which
is not a noticeable difference.
So you get these
mean differences,
but you've got to ask
about the effect size?
And the effect
size is very small.
If you correct for
socioeconomic status
because kids aren't randomly
assigned to schools,
it goes down to 1%.
That's not a
difference you can even
detect with your experience.
You need very large samples
and statistics to detect it.
And then finally, what looks
like systematic effects
of schools are often
genetic effects in disguise.
So one quick example of
this is that you probably
know that there is a big
GCSE difference between kids
in selective schools and
non-selective schools.
It's a whole grade difference.
That's a correlation between
going to a selective school
and how well you do on GCSEs.
But it's hard to
avoid interpreting
that environmentally.
The selective schools
have more resources,
better playing fields,
probably maybe better teachers,
but it isn't.
They're selecting for
genetically-influenced traits
of school achievement
and ability.
And it's a
self-fulfilling prophecy.
If you select the kids
who do the best at school
and have the greatest
ability, they're
going to do the best at school
and have the greatest ability.
If you correct-- you
merely just correct
GCSE scores for what
the schools select
on-- earlier achievement
and ability--
there's no difference
in performance.
There's no added value
of selective schools.
Now, a lot of parents will say,
but in their cups at least,
well, I'm not just
sending them there
to get better
school achievement.
You know, they get
better contacts.
Half of the judges in
the UK are from the 7%
of selective schools.
So maybe, there is an access
difference or whatever,
but if you're really just
thinking about achievement,
the evidence is that
it doesn't matter.
It doesn't make a difference.
Now, it might matter.
They might be
nicer places to be.
I'm not even convinced of that.
There's greater self-harming
at these selective schools.
My grandson got
a lot of pressure
because my son wanted
to send his kid to one
of these selective schools--
nearly 30,000 a year--
when he had a perfectly
good comprehensive.
And what was I going to say?
Well, just I resisted
that because I don't
believe it makes a difference.
Oh, yeah.
And a kid like him--
Tristram, no less-- is
a star in his school--
the comprehensive
elementary school.
But when these kids get to
these high-pressure selective
schools, they're
no longer a star.
They're lucky to
be kind of average.
And there's a lot of
pressure, and they
kick kids out if they don't do
well on the pretests and stuff.
I mean, it's a crazy,
stressful system
that I think destroys learning
and the enjoyment of learning.
So I think we need to
think about education
in a different way and
thinking about it genetically.
Most of what's going on is kids
are selecting, and modifying,
and creating
environments in part
correlated with their
genetic propensities.
So kids in the
same classroom can
experience different
environments based
on their genetic propensities.
They just ask more questions.
They follow up on stuff.
And I think we need to move
from this passive model
of imposed instruction, which is
the-- you know, instruction is
from Latin, [LATIN],,
to shove in,
which is the way we think of it.
We're shoving in this national
curriculum in their head.
Instead, we need to move to
an active model of shaped
environments in which
kids select environments
that are conducive,
that are fitting
with their propensities.
You know, not everyone--
this might be heresy here--
but not everyone needs to know
advanced math, for example.
So we need to think about what
kids are good at and maximize
their strengths and
minimize their weakness,
and mostly have them learn to
learn because it's well-known--
I mean, everybody says--
I don't if this is
true-- but that the kids
in elementary
school of today are
going to be doing jobs
that don't exist now.
They've got to learn to learn.
It's not a matter of specific
skills that they learn.
They need to learn to learn.
And mostly, they need
to enjoy learning.
But our test-obsessed
high-stakes testing culture
is really destroying any sort
of enjoyment of learning.
OK, I'll get off the soapbox.
And I would be happy--
that was 35 years
of my research,
and I would have been happy if
it ended there, but then along
came the DNA revolution.
And as I say, I think it's
going to change everything.
It'll allow us to predict from
DNA alone, problems and promise
from birth because your DNA
doesn't change throughout life.
And that allows us to
move towards prevention.
So rather than waiting
until problems occur,
like waiting till
kids go to school,
and then they fail
at reading, you
can predict reading problems.
And if you can predict
them, you can prevent them.
And prevention has got
to be a better way to go.
That's the way all of medicine
is moving towards prevention.
Don't wait till people have
heart attacks because we're not
very good at fixing things
like that, or obesity,
or alcoholism, or schizophrenia.
Let's predict who's
got the problems,
find out what those
processes are,
and intervene to
prevent the problems.
And then it really is
transforming science already.
Almost all large studies
now are including DNA.
And it will transform
society, parenting, as well as
education--
I'm writing my next book on
the genetics of parenting--
and then how we
understand ourselves.
The end of the book has the
world's first polygenic profile
for psychological
traits, and it's for me.
And so I describe
what does it mean
that I'm at the 94th
percentile for BMI--
Body Mass Index?
People say, oh, then you're
just going to give up,
say you're a genetic fatty.
But I know it's not the case.
For all of these problems,
it's motivating to say, OK,
I've got to work harder at it.
I've got to change
my environment
to make it less easy for me
to eat junk food, for example.
So it's important to know
about the DNA revolution.
And that's what I'd
like to talk about,
but I don't have to worry about
getting techy a little bit
with you guys, I suppose.
The first step is to get DNA.
If you've done any
direct-to-consumer testing--
ancestry.com, 23andMe--
you spit in a tube.
You can get DNA from
any cell in your body
because a remarkable thing--
you may not appreciate
this-- before you start life
as a single cell--
half the DNA from your mother,
half from your father--
that unique set of
DNA is the same DNA
in every cell in your body--
trillions of cells.
So you can get DNA from
any cell in your body.
Saliva actually
doesn't have cells,
but it does have cells
that are sloughed off
from inside your mouth.
That's partly what
saliva is doing.
So all you need is one cell.
If you drink from a cup,
MI5 can get your DNA
because you leave a cell or
so on the lip of the cup.
So once you get DNA, then
you genotype the DNA.
And there's, as I say,
only 1% of our DNA differs.
The most common type of DNA
difference is called a SNP--
Single Nucleotide Polymorphism.
Polymorphism is
just a difference.
And a nucleotide, it
refers to the bases of DNA.
So you know the DNA code is
written in a four-letter code
of A's, C's, T's, and G's.
So what this shows is
your two chromosomes.
And if you can see
the little letters,
you'll see that
those two chromosomes
have exactly the same nucleotide
bases, except for one.
And that would be true for us.
We're 99% similar, 1% differs.
And what we'll do is so
instead of having a C,
some people have a
T. Those are called
alleles-- alternate
forms of DNA.
And once we get
that difference, we
can just simply
correlate it with traits,
like academic achievement.
They call it
association in genetics,
but it's just a correlation
between whether you
have zero, one, or two
C's, for example, in that.
And here's the
first one that was
discovered using these new
techniques that I'll describe.
It was published in "Science."
And it was discovered using this
atheoretical approach that I'll
describe in just a
minute, but I just
wanted to show you what
a SNP looks like really.
This is a SNP where
we-- humans all
used to have TT at this
one particular locus
spot on the chromosome.
Then some guy had a mutation.
DNA is incredibly reliable
in its replication,
but when you've got three
billion base pairs of DNA,
every time your cells divide,
you're duplicating that.
Once in a great while,
you get a difference.
So this guy had an
A instead of a T.
He could have had
a C or a G, but he
had an A. It turns
out it rapidly
spread through human
populations, especially
in Europe where it
originally developed,
because it helps
you store body fat.
And back in the Stone Age,
that was a very good thing.
But you can imagine now
in a fast food nation,
it's not such a good thing to
be efficient at storing fat.
And so now, 40% of the
population has an A allele.
And if you have two
A alleles, as I do,
you're six pounds
heavier on average
than people who have
no A alleles, and then
people with one A
allele is in between.
So that's what we mean
by an association.
It's literally a correlation
between the zero, one,
or two A alleles and the trait--
in this case, body mass index.
Now, the thing that's
changed everything
is a technological
advance called a SNP chip.
So this is a DNA array the
size of a postage stamp
that consists of synthesized
short fragments of DNA that
surround a particular SNP.
And the method is
the same method
we've always used
to detect SNPs.
You denature-- you raise
the temperature of DNA,
and it separates.
And DNA doesn't like
to be separated.
It wants to find its mate.
You chop it up.
You put a fluorescent tag on
those little fragments of DNA.
And you wash them over this
plate that has these probes--
millions of probes-- for SNPs.
So what this cartoon at
the right-hand corner
is showing you, if you
have the right SNP,
it will hybridize because
DNA wants to hybridize.
But if you have the
wrong allele there,
it won't be able to hybridize.
So what you're left with
then is fluorescence
indicating whether or not you
have that particular allele.
And if you have a
strong signal, you
can see in this array on the
lower left, some of the dots
are brighter than others.
If it's dark, it means
you didn't have any.
If it's medium, it
means you had one.
And if it's very bright,
you had two of that allele.
And so you can study
millions of these SNPs
this way and very cheaply.
It started out with
thousands of pounds for this.
And now, the real costs
are more like 40 pounds
to do whole millions of SNPs
on this one little chip.
And it's very reliable, so
it's an amazing technological
advance that's really
transformed the life sciences.
So now, instead of correlating
one SNP with a trait,
you can correlate millions
of SNPs with a trait.
And it's atheoretical.
You don't just look at
a few candidate genes,
like serotonin because you think
it's important in depression,
which was a dead end.
Instead, you can take an
atheoretical approach just
saying, let's look at millions
of SNPs across the genome
and see if any of them are
associated with a trait.
That's called
genome-wide association.
And this is the thing
that's changed my career.
In the last year, there was a
genome-wide association study
published of
educational attainment
with over a million people.
And the reason
that's important is
that they could detect
very tiny differences.
Early on, these studies
weren't successful
because they weren't powered
to detect small effects.
Everyone thought
heritability is going
to be due to a few
genes of big effect,
but we never found those.
Instead, what you find in this
study and throughout the life
sciences is that
above that line is
genome-wide
significance corrected
for a million multiple testings.
And each dot is a SNP.
And SNPs close together
on a chromosome
are correlated with
each other, therefore
they should also be
correlated with the trait.
So these peaks suggest the
most significant results.
But the point is
thousands of these SNPs
are significantly
associated with a trait--
in this case,
educational attainment,
which is merely
years of education.
And this is what's found
throughout the life sciences--
there are no big effects.
That SNP I showed you
for body mass index,
people thought, well,
it's just a tiny effect--
1% of the variance.
It turns out it's one
of the bigger effects.
Most of the effects
are very much smaller.
So that's been a
startling revelation.
It means you need huge samples
to detect these effects.
But how are you going
to use them then,
if there's so many tiny effects?
If you want to study
gene-brain behavior pathways,
good luck because these
are such tiny effects.
It's hard to see them.
But I'm interested in
predicting behavior.
And you can do that by
adding up these SNPs,
just like you add
up items on a scale.
And you have to get them
in the right direction.
And you weight them
by the effect size
of their association,
just because a SNP like
these count for more
than some of these SNPs
that are less associated,
but it's just simply
adding them up.
And that's a polygenic score.
And this is what's
transforming everything
because they're 100% reliable.
They're unbiased.
They're cheap.
But unlike any other
predictor we have,
you can predict just
as well from birth
as you can from later in life.
And most of what we know
about prevention in medicine,
as well as in psychiatry,
even think of obesity,
it's earlier preventions
that work best,
but we can't predict earlier.
But we can now with DNA.
And it's one of the
few correlations that
do an imply causation
in the limited sense
that there is no
reverse causation.
You inherit your DNA sequence
and nothing changes that.
And before you ask me about
epigenetics or gene expression,
yeah, these SNPs
have to be expressed,
but if they're associated with
a trait like school achievement,
they were expressed.
We don't have to know anything
about the pathways in between.
And nothing in behavior,
environment, or the brain
changes your DNA sequence.
So this is really happening.
People worried about
this 10 years ago,
but then direct-to-consumer
companies like 23andMe,
ancestry.com came along.
And 25 million people have
voted with their checkbook
to do this-- to pay
for it themselves.
Mostly what you get are
single-gene disorders.
And most people
do it for ancestry
because it is fascinating.
You might think you know
your ancestry, but you don't.
We're all mongrels and we
come from diverse parts
of the world.
And we have a lot of relatives
out there we didn't know about.
There's some great stories.
I just saw that BBC documentary
last month about diblings--
donor-inseminated siblings-- who
don't find out till they're 18?
There's one father who's
inseminated 65 kids,
so they're actually
half-siblings who
didn't know about each other.
So it's a wild west out there.
And what they're not doing
yet is these polygenic scores,
but that's the big thing now.
They're all struggling to do it.
A new company came
up this week that's
trying to sell polygenic scores.
23andMe won't do it because they
were burned by FDA for reasons
we can go into.
So they allow you,
if you do 23andMe,
with one push of a button, you
download all your genotypes.
And these other companies
with one push of a button,
you upload them, and
then they give you
these polygenic scores.
And so the big news is
it's not announced yet,
but it's really cool that
the NHS, the government
has just given 80 million
pounds to make genotyping free
on the NHS.
So when you go to the
hospital beginning next year
and they take blood,
you'll be asked,
do you want to do this and how
much information do you want?
And when they've done this
in Finland and Estonia,
they're oversubscribed
right away.
85% of the people want to
do it because in a way,
it's so much better than
direct-to-consumer companies.
In terms of data
confidentiality for example,
they're not going to
sell it on to pharma
as 23andMe does anonymously.
And also if you do 23andMe
and you're in the unlucky 1%
of the population who has two
alleles for this recessive
trait for Alzheimer's, you could
find out you're at a 60% risk
for having Alzheimer's.
And what do you get from them?
A link saying you might
want to find out more
about Alzheimer's, but there's
nothing you can do about it.
So if you had it
with the NHS and you
have NICE-- the National
Institute for Clinical
Excellence-- they could
decide you can't do everything
for everybody.
There's some things you
can't do anything about.
So probably, the
standard procedure
will be do you want to just
know the stuff that NHS
thinks you ought to know about?
Certainly, heart attacks
because you can predict those
from early in life and you
can prevent heart attacks.
Alcoholism?
You know, it's not that
good a polygenic score,
but you cannot become alcoholic
unless you drink a lot
of alcohol for a long time.
If you drink as much
as your friends,
they might not be at risk for
alcoholism, but you might.
So there are things like
that that you might really
want to know about.
And this is 160
million are behind this
if it works well with the
first five million people.
So the only thing
is you have to agree
to make your NHS electronic
records available for research
anonymized because
the idea is to get
bigger and bigger
samples to detect
smaller and smaller effects.
So here are the big
ones in psychiatry.
A lot of work has gone into
severe mental disorders.
This is bipolar and
major depression.
And with schizophrenia,
you can predict
7% of the liability
towards schizophrenia.
Now, it's maybe 50% heritable,
so it's a long way to go,
but this is all just
in the last few years
once we recognized that the
biggest effects are very small.
But the star, and
the thing that's
really been amazing
to me, is that we
use the educational attainment
genome-wide association
study to create polygenic
scores for kids in my TEDS
project-- the twins project.
So 7,000 kids, we
create their score
for educational
attainment, which means
years of schooling completed.
Well, they're 16, so they
haven't completed school,
right?
But I was interested in saying,
how much of the variance
will we predict in tested
school achievement?
And the answer is we
predict 15% of the variance
in school achievement, more
than you predict for the target
trait of educational attainment
in adults, which is 10%.
And this is the
strongest prediction yet
in the behavioral sciences,
explaining 15% of the variance.
School achievement
is 60% heritable,
so we've got a long way to go.
I have no doubt in a few
years, we'll be at 30%.
It's a technical
problem to get to 60%.
We're going to need
whole-genome sequencing
because the SNPs
we use are great
and we've got millions
of them, but there's
a lot of the genome we're
not tagging with them.
So that's the next big thing--
whole-genome sequencing.
But right now, 15%
of the variance
is a lot of variance to explain.
You think of OFSTED
ratings of school quality
explaining 4% of the variance.
This is better
prediction than you
can make from income and
SES sort of variables
of the family.
And I just wanted to show you
this in a bit more detail.
If you take this correlation
of a 0.4 for the sample,
now we take the sample now
and divide the 7,000 kids
into equal groups
of 100 deciles.
And you can see that there
is a linear relationship.
The y-axis is GCSE scores.
The higher the polygenic score,
the higher the GCSE scores.
But there's a big
difference at the extremes,
even though we're only
explaining 15% of the variance.
The average grade at
the bottom decile is a C
and the average grade of the
upper decile is an A-minus,
but it's only 15%
of the variance.
So an important point
to emphasize here is--
I don't if you can
see the yellow dots--
this is a box plot.
So it means the kids
in the lowest decile,
75% have a grade of C or lower,
but 25% have a higher grade
and some of them have
grades in the A's.
It's not a perfect prediction.
Conversely, the kids in
the highest group, 75%
have an A-minus or greater,
but 25% have a lower grade.
But that's what will always be
the case because heritability
isn't 100%, so we'll
never explain it all.
And of real-world
significance even
now is 25% of the kids
in the lowest group
go to university and 75%
of those in the top group
go to university.
So this is a real difference.
And we need to think
about how we're
going to deal with this in
education and in parenting.
So right now, all we've
got is this coarse variable
of educational
attainment, but there's
a lot of work being done on
more specific polygenic scores
for reading, for STEM
subjects, and for ADHD.
And I think it might help
with personalized education,
where we don't just have a
one-size-fits-all educational
system.
We recognize that
kids are different,
and we try to go with that.
And if you can predict
problems as in medicine,
I think that will lead
towards more preventative work
rather than waiting
until problems occur.
And here's something
people don't
recognize is siblings
in a family are
50% similar genetically.
That means they're
50% different.
And people don't really
realize how different that is.
So you can have kids
in a family where
one kid did very well at
school and the other one is not
doing well, but it could
be they have a very
different polygenic score.
You know, it could be
all over the place.
You could have one that's
two standard deviations
above the mean and one that's
two standard deviations below.
And this is the thing
that always comes up
in education is selection.
And my view, just
based on values,
is we shouldn't have selection.
But if you do, I don't
see any logical reason
why you could argue against
using polygenic scores
to supplement tests because
at least they're not biased
and you can't get a better score
if you buy an expensive tutor,
for example.
So they add something
to the prediction.
And I'm particularly
interested in the possibility
that they could be useful in
the most socially disadvantaged
families, where the kids don't
have the [INAUDIBLE] to deal
with academic training.
So what I've tried to say is
that inherited DNA differences
are the major systematic
force making us
who we are, being
responsible for how
our children do at school.
The environment is important,
but it's not systematic.
It's these random chance
variables, not systematic
effects of families or schools.
And that polygenic scores
will transform science.
It's already happening.
All big studies
now are including
DNA to add a genetic component
to what they're doing--
society, parenting,
schools, and also
how we understand ourselves.
Thank you.
[APPLAUSE]
SPEAKER 1: Thank you very much.
We do have about 10
minutes for questions.
Please wait for a microphone.
AUDIENCE: Hey.
Thanks for the talk.
So on the genome-wide
association studies,
you mentioned that
these are correlational,
but that generally
implies causation.
And it's true there's no
reverse causation here,
but don't things like
assortative mating increase
those, bias those
estimates upward?
And I guess the
extreme case would
be you could imagine a
genome-wide association
study that would test for
a country of birth, right?
Like, and is it
possible that genetics
would have impact [INAUDIBLE]?
ROBERT PLOMIN: Yeah.
Well, this is like condensed
from three hours of talk
and it's discussed in the book.
That's a very good point that
as I said at the beginning,
we only describe
particular populations
at particular times.
And the populations that
are in these big genome-wide
association studies are almost
entirely Northern European,
American, Australian.
They're Caucasian
populations, so these scores
describe that
population pretty well.
So it describes
people in England,
but it doesn't describe other
ancestry groups for example.
And the way you
deal with this is
you take out principal
components from these analyses.
So this is all the life
sciences doing this stuff
and it's some of
the brightest people
around, so that's well-covered.
The issue of assortative
mating is a tricky one
because if you're interested
in predicting how well kids
do at school, part
of their genetics
is whether or not there's
assortative mating.
You know, like begets like.
Opposites attract.
Uh-uh.
It's only like begets like.
It's assortative-- positive
assortative mating.
So if you don't believe in
intelligence, be single,
go to a singles bar.
And in a few minutes, the
first thing you're picking up
is how bright someone is,
especially verbal intelligence.
So for personality,
the correlation
is 0.1 between spouses.
For non-verbal
ability, it's 0.4.
And for verbal
ability, it's 0.6.
I mean, you don't really know
somebody's spatial ability
very well when you talk to them,
but you very quickly pick up
on whether they're
going to be worth
talking to in the morning.
So that's assortative mating,
and it's part of the genetics.
It's getting at mechanisms.
If you want to
understand the mechanisms
by which this occurs, great.
But if you're interested
in prediction, it's OK--
assortative mating.
And it really is only
for cognitive abilities
that you get this
assortative mating.
But it's a great
question and there's
tons of stuff about this.
And so it'd be nice to be able
to go on about it some more,
but I think we'll have to
leave it there for this.
AUDIENCE: Thanks.
ROBERT PLOMIN: Thank you.
AUDIENCE: Thanks for the talk.
So in the study about
the polygenic scores
and essentially
the effect sizes,
if you have a million people
and you have a lot of SNPs,
how can you, like, detect
the effects and interactions
between different
small effect sizes?
ROBERT PLOMIN: Great question.
I'll repeat it because that
mic is only for the recording.
It was a question about if
you have these small effects,
how do you correct for
looking at millions of SNPs?
And the second part was?
AUDIENCE: Essentially, if
you consider interactions
between small effects, right?
ROBERT PLOMIN:
Interactive effects.
So again, a lot
to say about that.
That's a very
pertinent question.
But as I showed you, we're
correcting for a million tests.
So that line of significance
corrects for a million tests.
Even though you have
more than a million SNPs,
those are linkage groups.
So it's thought that
correcting for a million test
works, and it does
because what you do
is you create these
polygenic scores
from the genome-wide
association data in one study,
but then you apply them
in independent samples.
And what people realized right
away is if you take 100 SNPs,
it doesn't predict
nearly as well as 1,000,
doesn't predict nearly as
well in independent samples
as 10,000.
But as you rightly
are intuiting,
these are additive
effects of each SNP.
And most people think genetic
effects must interact.
Well, they do at a
mechanistic level,
but fortunately for
us, they don't when
it comes to adding up
the effects of genes.
You get most of the
effect of heritability
from adding up these genes.
And in a way, that's the way
selection works in evolution.
It works on additive
genetic variance.
But you know, it's
hard to believe,
but quantitative genetic
studies, twin and adoption
studies, and animal
selection studies
are all consistent
with the notion
that genetic effects
are largely additive.
Because the problems of power
would be so much greater
if you have to deal with not
just interactions between two
genes, but what about
10 genes or 100 genes?
AUDIENCE: Thank
you for the talk.
I'm a physicist
by training, so I
have to ask somewhat
sort of trade,
some of the more
fundamental perspective
of, if I understand
correctly, DNA
determines what proteins
are produced by the body.
Which means that if we
inject those proteins which
make people in quotes, smarter,
then that study potentially,
this study could be potentially
interpreted like today
you can do a test even in
the UK before the child is
born for severe
genetic disorders
and potentially terminate
a pregnancy early.
And one can imagine
that some people won't
want kids which have
predisposed to be
less performant at school.
But at the same
time, these studies
could be interpreted
as a way to develop
medicines, which make people's
cognitive abilities higher.
It does make sense.
ROBERT PLOMIN: Yeah, so
you started off by saying,
you're talking about single
gene, simple gene protein
sort of relationships.
And it's all a lot
more complicated.
All these genes do many,
many different things.
And each thing,
even in the brain,
is influenced by
many, many genes.
So it's going to be hard to take
like a gene editing approach
for these complex disorders and
traits influenced by thousands
of DNA differences.
Where people are really
thinking about it though,
are in terms of
single gene disorders.
That's where gene
editing comes in.
But you have to, there was this
crazy BBC documentary on beauty
and how we could do gene
editing for beautiful.
But you see, you've
got trillions of cells.
How are you going to change
all of your cells as an adult?
All you can do with gene
editing is get in there
at the first stages.
But you'd have to
change every cell.
But people are trying to do
that for single gene disorders
with gene editing, this CRISPR
technology, which is amazing.
But I don't think
it's going to work
when you're dealing with
these thousands of tiny DNA
differences.
But another good question.
SPEAKER 1: For
one more question.
No one has one?
We can finish here?
So, thanks a lot again.
ROBERT PLOMIN: My pleasure.
Thank you all.
[APPLAUSE]
