there will be people who object. There will be people who will
say that this is a revival of racial science. Perhaps so. I would
argue, however, that even if this is a revival of racial science,
we should engage in it for it does not follow that it is a revival
of racist science. Indeed, I would argue, that it is just
NATURE OF NORMAL HUMAN VARIETY
A Talk with Armand Leroi
the early '90s, I was visiting Cambridge and went out to dinner
with the late Stephen Jay Gould. During a long evening of conversation
we talked about his ideas concerning race, racial racial differences,
racial equality, including his well-known writings on the use
and misuse of IQ tests and other such measures. I came away from
the conversation with the distinct sense that he believed there
were some things better left unsaid, some areas of investigation
that were out of bounds if he wanted to have a just society.
Nothing strange here. His views were, and still are, consistent
with the daily fare of the editorial pages of many of our important
newspapers and magazines.
Leroi, a biologist at Imperial College, feels differently.
He loves what he calls "the problem of normal human variety".
uniquely among modern scientific problems, he says, "it
is a problem that we can apprehend as we walk down the street.
We live in an age now where the deepest scientific problems
are buried away from our immediate perception. They concern
the origin of the universe. They concern the relationships
of subatomic particles. They concern the nature and structure
of the human genome. Nobody can see these things without large
bits of expensive equipment. But when I consider the problem
of human variety I feel as Aristotle must have felt when he
first walked down to the shore at Lesvos for the first time.
The world is new again. What is more, it is a problem that
we can now solve, a question we can now answer. And I think
"Of course, there will be people who object. There will be people who will
say that this is a revival of racial science". Leroi argues that "there
will always be people who wish to construct socially unjust theories about racial
differences. And though it is true that science can be bent to evil ends, it
is more often the case that injustice creeps in through the cracks of our ignorance
than anything else. It is to finally close off those cracks that we should be
studying the genetic basis of human variety."
a Reader in Evolutionary Developmental Biology at Imperial
College, London. He is the author of Mutants: On Genetic
Variety and the Human Body, winner of The Guardian First
Book Award, 2004.
NATURE OF NORMAL HUMAN VARIETY
question that interests me, as it does so many other people,
is how to go about making a human being. It's a very difficult
problem. Roughly what it boils down to is this: We have 30,000
genes or so. It's often said that the genome is something in
the nature of a book. It has words, a grammar, a syntax, and
of course those words have meaning. The only problem is that
we don't know actually what that meaning is. So the question
is, how do we decipher that? And turning that question around,
looking at it from the point of the human body, what do those
genes mean to the construction of the human body?
Of course, I myself don't actually work on humans. They're just too inconvenient.
I work on worms. This worm is Caenorhabditis elegans, for which Brenner,
Sulston, and Horvitz just won the Nobel Prize. And the reason why I and a
thousand other scientists work on this worm is that, for all of their marvelous
properties, it's easy to keep thousands of them in petri dishes, and it's
very easy to find mutants. And that's the critical thing. We find mutants
that interrupt particular genes, and that tells us what those genes do and
what they mean to the body of a worm.
Developmental biologists have been doing this for a long time—once
a field has its Nobel, you can be sure it's reasonably mature. What people
haven't really done, however, is to do this for the human body. The reason
is obvious: you just can't go out and generate mutants in humans. For humans
you've got to go out and find those mutants. But they're out there. There
are thousands upon thousands of mutants out there—no, more, millions—no,
actually billions. This is because we are all mutants. That's one thing you
don't expect but which happens to be statistically true. Each of us carries
mutations that interrupt particular genes. So if you can just find who is
a mutant for a particular gene, and examine what they look like, you can
actually then work out what those genes do.
This raises a question: what exactly is a mutant? Worm biologists and fly
biologists—geneticists generally, working on model organisms—use
the word "mutant" in a very particular way. In worms and flies
there is an arbitrarily defined strain which we call the "wild type".
But in humans there is no arbitrary wild type. So can you, in fact, speak
of mutant humans?
You can, but the definition of what is a mutant in humans is necessarily
more roundabout. This is because we have such an extraordinary amount of
natural variation in our species. If you go around the world you see tall
people, short people, red-haired people, brown-haired people, people with
curly hair, people with no hair, and so on. Given all this variation, what
exactly, and who exactly, is a mutant? It's an important question, because
to say something is a mutant is in fact to make an invidious distinction.
This is to say something is not just different but actually abnormal in some
fashion. Yet despite the fact that there is so much variation in our species,
it is actually possible to speak in a coherent way of mutations and of mutants
Roughly, the reason you can do this is as follows: If you look at the coding
sequence, more precisely, the protein sequence produced by any given gene,
it's the case that for most genes nearly everybody has the same version.
True, there are some genes that are polymorphic — variable — and
these are genes that give us all our natural diversity. But they actually
constitute a very small fraction of the genome. Most people have the same
functional version of a gene. Given that fact, you can define a mutant as
somebody who has a rare variant of a gene, moreover, a variant that harms
him in some fashion. And if you look at it that way, it's clear that we all
carry rare variants that do us harm in some way, and that we are in fact
We can even put some numbers on this. One of the really surprising results
in recent years, which comes from the comparison of the genomes of different
species, is that every newborn child carries three novel deleterious mutations,
that is, mutations that its parents didn't have. Not only that, but each
child inherits at least some of the mutations that its parents have as well.
It's estimated then — and of course this is just an estimate — that
every newly conceived person has something like 300 mutations that affect
its health for the worse in some fashion.
Of course, that number doesn't tell us a whole lot. We not only need to know
about the number of mutations that we have, but also the distribution of
their effects. This is because some mutations have very severe effects. They
are the mutations that cause the big known inherited diseases — and
about 10,000 such diseases have been identified so far. But there must be
many, many more mutations that do us harm, but only subtly so. These are
the mutations that give us weak eyes, bad backs and the like. These are mutations
that we know very little about but that statistically speaking must be there.
It's actually in these mutations that a lot of human health lies—or
rather the absence of human health lies. At least it does once you have gotten
rid of the contagious diseases.
When I speak of mutations that do somebody harm what I really mean is not
so much that they just affect physiological health; what I really mean is
they affect the Darwinian fitness, the probability that they will reproduce.
It's an evolutionary definition. It's the kind of definition that can encompass
an enormous range of impairments, and the kinds of impairments that you see
that are caused by mutations are at times of a degree and of a form that
you really just cannot conceive of.
If you go to teratology museums—literally "monstrosity museums"—in
places such as Amsterdam and Philadelphia, you can see rows of babies in
bottles. These infants, usually stillborn, are deformed in ways that are
truly hideous, that really represent the kinds of monstrosities that you
might expect from Greek myth. I mean this quite literally. They include children
born with a single eye in the middle of their forehead, and who look exactly
like the monsters of Greek myth—Polyphemus in The Odyssey, for example.
Indeed, it's sometimes suggested that the monsters of Greek myth were inspired
by deformed children, and this seems to be a fairly remarkable correspondence,
at least with some of them.
These infants, when you see them, are truly horrific. But very quickly, after
you look at them, a sort of intellectual fascination takes over because it's
clear that these children tell us something very deep about how the human
body is built. Take, for instance, these children with a single eye in the
middle of their foreheads. The syndrome is called, appropriately, Cyclopia.
Cyclopia is caused by a deficiency in a gene called Sonic hedgehog. Sonic
hedgehog is named after a fruit fly gene which when mutated causes bristles
to sprout all over the fruit fly larva, hence "hedgehog". When
the gene was found in mammals, some wit called it Sonic hedgehog after the
video game character. If you get rid of this gene, bad things happen. You
lose your arms beneath the elbow and legs beneath the knee. The face collapses
in on itself, such that you get a single eye in the middle of the forehead
and the rest of the face collapses into a long, trunk-like proboscis. The
forebrain, which is normally divided such that we have a left and a right
brain—the left and right cerebral hemispheres—is fused into a
single unitary structure. Indeed the technical name for this syndrome is
Now all this is very horrible, and actually that's just an initial list of
things that can go wrong in infants that have no Sonic hedgehog. But what's
really interesting about it is that by looking at infants of this sort you
can reverse-engineer and ask what Sonic hedgehog does in the embryo. Instantly
it tells you that one of the things that Sonic hedgehog does is to keep our
eyes apart because if you don't have the gene the face collapses. It also
separates the left and and right sides of our brains. And it's needed for
the formation of our arms and legs. In fact, it is one of the most ubiquitous
and powerful molecules in the making of our bodies.
And other, more subtle mutations, tell more about it. For example, just as
having too little Sonic hedgehog causes the face to collapse in upon itself,
having too much causes it to expand. I was recently in San Francisco, in
Jill Helms's lab at the University of California, San Francisco, where she's
got a jar containing the head of a pig. Or is it two pigs? It's just not
clear since the jar contains a pig with two faces, two snouts, two tongues,
two throats, and three eyes. It's not a Siamese twin pig; it's just a pig
with two faces. Chickens and pigs with two faces crop up periodically, as
indeed do humans with two faces, or nearly two faces. There's a syndrome
in which you have eyes that are very widely spaced from each other, and in
which the nose becomes duplicated. You have two noses side by side in two
varying degrees of development.
The gene for this syndrome has recently been cloned, and guess what? It turns
out to be the gene that controls Sonic hedgehog, and that, in fact, switches
it off. People with the syndrome have too much Sonic hedgehog just as infants
with Cyclopia have too little. So by looking at a range of these kinds of
syndromes you can put together a very complete picture of how a gene like
Sonic hedgehog controls one particular feature of us, the width of our faces.
It's a very mundane thing that you'd hardly think about, but that seems to
be controlled by this genetic system.
There are many other disorders that equally informative. The star at the
Mütter Museum at the College of Physicians of Philadelphia is Harry
Eastlack, a man who had a disease called Fibrodysplasia Ossificans Progressiva.
It's a disorder in which supernumerary bones form. The Mütter Museum
has his skeleton, which he donated at the time of his death when he was in
his forties. The skeleton is essentially not one man's skeleton—it
is, as it were, one skeleton encased in another. What happens in this disorder
is that wherever you get a bruise or a wound, instead of normal cells moving
in to regenerate the skin and the flesh and heal the wound, bone forms. So
every bruise turns to bone. The kids are born relatively normal, but as they
go through life bone accretes all over them such that they can no longer
move. They become rigid, locked into place. You can cut it away, of course,
but as soon as you make an incision, and that incision heals, more bone forms.
So it's a vicious circle. We don't know which gene is mutated in this syndrome.
But it's almost certainly got something to do with bone morphogenetic protein,
a protein that is, as the name suggests, normally involved in making bone
in infants. It's just that in most of us this gene switches off. In these
people this protein keeps on being produced throughout life, especially when
there's a wound. It's another marvelous instance of how a given mutation
can tell us something important about how bones are formed. FOP is a very
rare disorder, and the reason why the gene hasn't been cloned is because
to identify genes, to clone genes, you need to have big pedigrees. At least
it helps. But these people just never have children.
People sometimes ask what developmental biology is good for. We can identify
genes that are responsible for making this or that part of the human body.
But in humans, of course, there's a very pressing question: namely, how can
you fix the deleterious consequences of these mutations? It's one thing to
go into a clinical genetics ward, a pediatric ward, and study kids who are
seriously deformed, and say, "This is just terribly interesting. Your
son is highly informative about the function of the Jagged-2 gene." — but
that's not a great deal of comfort to the parents who actually have to deal
with raising children who are variously deformed and may die or, at the very
least, have to undergo a great deal of surgery. That, of course, is the problem.
The molecular biology is beautiful, but when it actually comes to curing
people, you just have surgery — which is little more than a rather
sophisticated form of butchery.
The great promise, of course—and it's been a promise for years now
and will remain so for some time—is that by learning about what genes
do and how organs and tissues are constructed we can reconstruct them as
we wish. By working out the program we can take cells, put them in a test-tube,
and rebuild tissues. You don't have cartilage in your larynx? We can build
it for your child, and we can fix it. You don't have a breast? We can rebuild
that, too. And so on. This is a whole new area called tissue engineering.
There are big institutes devoted to it now, where engineers, materials scientists,
and molecular biologists are all working together. So far, it must be said,
it's more institution building and propaganda than real results, but it'll
happen. That is when the justification for this whole science will ultimately
There's no doubt that when you see some of these children who are so terribly
deformed, it's very difficult. It's shocking, it's heartbreaking, and if
you spend any time with them, whether they're alive in pediatric wards, or
whether they're just babies in bottles, it takes a real psychological toll.
I certainly don't ever get completely hardened to it. But what is also true
is that intellectual fascination of seeing what has gone wrong in these unusual
bodies takes over. This is especially the case when your eye is attuned to
perceiving the differences in detail, once you see that it's not just arbitrary
deformity, once you understand what you are really looking at are the outcomes
of the laws that regulate and make the human body. When this happens, deformity
acquires a real beauty. It's a beauty that emerges from answering one of
the oldest questions in biology: namely, how are we put together?
that's intellectual beauty. What of human physical beauty?
This is something that interests me greatly. I'm not interested
in the general aesthetic question here, but ourselves. Some
people say that beauty is uninteresting and that it's just
a matter of taste. I don't think so. I would say, and there
are others who would certainly agree with me, that we have
a general psychological program from which stems a universal
notion of beauty. Incidentally, this idea that we all perceive
certain features to be beautiful is one that Darwin would have
disagreed with. Darwin believed that the perception of beauty
was particular to particular peoples in particular times and
places. He was probably wrong, or at least he was only partly
right. I won't attempt to justify that answer, but I think
it to be true. These days, the general thinking tends to be
that there's a universal notion of beauty which is true for
people around the world. And the question is, what is that
and what drives it?
Many people think that beauty is a certificate of health; this is an idea
that comes out of sociobiology. But it is more obvious than than that. It's
simply the idea that beautiful people are healthy people and we search for
healthy mates. And that's probably true. Or at least it was. But is it still?
In the past, health was primarily a matter of environmental conditions—your
exposure to contagious diseases and the amount of food that you had when
you were growing up. Rich people had better environments, hence the positive
association between beauty and wealth. But what of modern economically egalitarian
societies such as Holland? In such societies, does the ancient association
still obtain? If the variance in beauty is due to the variance in the quality
of the rearing environment then it must be the case that the Dutch — who
all eat much the same good food, live in much the same well-designed houses,
and have access to much the same excellent health-care — must all be
equivalently beautiful. But is this so? The answer is, of course, no. Among
the Dutch you can find good-looking and not so good-looking people. And the
question is then, why?
I would argue that the reason for this is that there is and will always be
variance in beauty is because there is variance in mutational load. What
is beauty fundamentally about? I would argue — and this is really just
a postulate at this time, but it is one that interests me a great deal — that
the fundamental reason why some of us are more beautiful than others is because
of those deleterious mutations that we all carry We may carry 300 deleterious
mutations on average, but there is of course a variance associated with that.
Not everybody has 300. Some people have more, some people have fewer. If
this is true—and statistically it must be true — then someone
in the world has the fewest mutations of all. Someone in the world is the
least mutant human of all. Indeed, we can actually calculate, making some
assumptions about the shape of the distribution, how many mutations that
person has — and it turns out to be 191 versus the average of 300.
This, to my mind, is surprisingly many. I would suggest that if we could
find that person, he or she would be a good candidate for being the most
beautiful person in the world. At least she would be, assuming she did not
grow up in some impoverished underdeveloped nation. Which, statistically,
she will have done since most people do.
one more thing that I should like to know about, and that is
the nature of normal human variety. There are tens of thousands
of geneticists around the world, all of whom are busy identifying
the genes that cause human disorders of one sort or another.
Historically they began with the really easy ones, the big
congenital disorders, especially those that allow people to
survive and produce children and so have big pedigrees that
allow them to map the genes. Now the emphasis has shifted to
studying the genetic basis of more subtle and more complicated
kinds of disorders, things like diabetes and cancer, that have
lots of genes that underlie them each of which has a small
effect. This is a much more difficult task, but people are
doing it because these are the inherited diseases that affect
But there's one aspect of human inheritance that people are resolutely ignoring.
And that is normal human variety. Or, to put it more crisply: race. If we
look around the world we find that people look very different from each other.
These differences are manifestly genetic. They must be. That's why people's
kids look like them. Yet we know nothing about that variety. We don't know
what the differences are between white skin and black skin, European skin
versus African skin. What I mean is we don't know what the genetic basis
of that is. This is actually amazing. I mean, here's a trait, trivial as
it may be, about which wars have been fought, which is one of the great fault
lines in society, around which people construct their identities as nothing
else. And yet we haven't the foggiest idea what the genetic basis of this
is. It's amazing. Why is that?
The reason is two-fold. The first—which is not such a trivial problem—is
that skin colour is not controlled by one gene. If it were only one gene
we'd know it. It's many genes—more than three but certainly fewer than
30. It's a difficult problem, although, frankly, it's not such a difficult
problem that if geneticists really wanted to solve it, they couldn't. It'd
be easy enough to do if they put a fraction of the effort that went into
discovering the BRCA1, the breast cancer gene. I'm not saying they should;
finding the breast cancer gene is more important than discovering the genetic
basis of white and black skin, but still, it's not a technically impossible
thing to do.
But of course the fundamental reason why people don't do it is because it's
race genetics. It's because of the long and sorry history of genetics and racial
differences. And indeed, more than that, the whole thrust of genetics since
the war has been to argue that races don't exist and that they are just social
constructs. This is very much the Harvard School — Dick Lewontin for
example has been one of the big proponents of this point of view. The late
Steven Jay Gould was another.
After the Second World War, when the enormities of Nazi science really hit
home — which were in turn the consequence of a much larger racial science,
not just in Germany, but everywhere—all right-thinking scientists made
a resolute effort to ensure that science would not be bent to such evil purposes
again. They were determined that science would never again be used to make
invidious discriminations among people. The immediate result of this was
the UNESCO Declaration on Race in 1950, fronted by Ashley Montagu and backed
up by geneticists such as Theodosius Dobzhansky which affirmed the equality
of races. Then, in the 1960s, Dick Lewontin and others discovered that gel
electrophoresis could be used to survey genetic variation among proteins.
These studies showed that humans have a huge amount of concealed genetic
variation. What is more, most of that genetic variation existed within continents
or even countries rather than among them. UNESCO said races were equal; the
new genetics said they didn't exist. Finally, moving a few decades on, the
Out-of-Africa hypothesis of the origin of Homo sapiens comes to the fore,
and multi-regionalism falls from fashion as it becomes clear that humans
are not only a single species — something which we've known since Linnaeus'
day—but a single species that has only diverged into sub-populations
The result of this history — which has been partly driven by data,
and partly by ideology — is that these days anthropologists and geneticists
overwhelmingly emphasise the similarities among people from different parts
of the world at the expense of the differences. From a political point of
view I have no doubt that's a fine thing. But I suggest that it's time that
we grew up. I would like to suggest that actually by emphasizing the similarities
but ignoring the differences, we are turning away from one of the most beautiful
problems that modern biology has left: namely, what is the genetic basis
of the normal variety of differences between us? What gives a Han Chinese
child the curve of her eye? The curve I read once described by an eminent
Sinologist as the purest of all curves. What is the source of that curve?
And what gives a Solomon Islander his black-verging-on-purple skin? Or what
makes red hair?
Actually, the last is the one thing we do know. It turns out that red hair
is due to a mutation in a gene called MC1R, melanocortin receptor 1, which
controls the production of p eumelanin, black pigment, versus red pigment,
phaeomelanin. Rather marvellously, it also turns out that mutations in MCIR
also cause red hair in red setters, Scottish cattle, and red foxes. But we
don't know what causes brown eyes versus blue eyes versus green eyes. We
know very little about the variation in normal human height. We don't know
why some girls have big breasts and some of them have small breasts. These
are important questions — or at least jolly interesting ones—and
we just don't know their answers.
The reason I love the problem of normal human variety is because, almost
uniquely among modern scientific problems, it is a problem that we can apprehend
as we walk down the street. We live in an age now where the deepest scientific
problems are buried away from our immediate perception. They concern the
origin of the universe. They concern the relationships of subatomic particles.
They concern the nature and structure of the human genome. Nobody can see
these things without large bits of expensive equipment. But when I consider
the problem of human variety I feel as Aristotle must have felt when he first
walked down to the shore at Lesvos for the first time. The world is new again.
What is more, it is a problem that we can now solve, a question we can now
answer. And I think we should.
Of course, there will be people who object. There will be people who will
say that this is a revival of racial science. Perhaps so. I would argue,
however, that even if this is a revival of racial science, we should
engage in it for it does not follow that it is a revival of racist science.
Indeed, I would argue, that it is just the opposite. How shall I put it?
If you want to prove, what most of us believe, that skin colour does not
give the measure of a man, that it tells nothing about his abilities or temperament—then
surely the best way is to learn about the genetics of skin colour and the
genetics of cognitive ability and demonstrate that they have nothing to do
with each other? The point is that there will always be people who wish to
construct socially unjust theories about racial differences. And though it
is true that science can be bent to evil ends, it is more often the case
that injustice creeps in through the cracks of our ignorance than anything
else. It is to finally close off those cracks that we should be studying
the genetic basis of human variety.