[MUSIC PLAYING]
SEAN CARROLL: Devon and Skye Cooper are brother and sister.
Both of them have sickle cell anemia.
Before the advent of modern medicine,
sickle cell anemia almost certainly
meant death before adulthood.
[BEEPING]
Even today, young patients can suffer strokes and organ
failure.
Sickle cell anemia is a genetic disease.
Parents of those who have the disease
might not have it themselves, but both
must carry the sickle cell character in their DNA.
MATTHEW HEENEY: So how's it going?
Good.
Can I see your hands?
This is pretty.
Where'd that come from?
Is that from Brooklyn?
SEAN CARROLL: Beside some bone pain,
Skye leads the fairly normal life of a 13-year-old girl.
But her younger brother Devon has suffered acute chest
syndrome, and has already had his spleen removed.
MATTHEW HEENEY: So you don't get any more belly pains?
That's good.
SEAN CARROLL: Skye and Devon's symptoms arise from the fact
that some of their red blood cells become misshapen--
crescents instead of disks--
preventing enough oxygen from being delivered
to all parts of the body.
It's not completely clear why symptoms are variable.
But what is most perplexing about sickle cell disease
is that it's not rare.
MATTHEW HEENEY: So in the United States,
we think there are between 70,000 and 125,000 persons
with sickle cell disease.
However, that doesn't take into account immigration
and other patients or persons coming from other parts
of the world into the country.
SEAN CARROLL: In fact, in some populations--
African-Americans, for example-- the incidence is as high as one
in 500, astoundingly high for a deadly inherited disease.
Didn't Darwin teach us that harmful traits
disappear from the gene pool through natural selection?
Why is sickle cell anemia is so prevalent, and why,
in particular, among people of African descent?
The answers to these questions began with a remarkable set
of observations from an unlikely person more than 60 years ago.
Tony Allison has spent most of his career
as a medical doctor and molecular biologist
in the US and England.
But he grew up in East Africa.
And he's quick to recall his formative years in Kenya.
ANTHONY ALLISON: The point is that we lived in the upcountry.
And we used to go to the coast every year
in August for the holiday, when it was a little bit cooler
than at other times.
So we had the trip all the way down,
which was usually with a truck and a Car
And so we would camp on the way in in Tsavo.
And there would be lions roaming around.
So it was really quite exciting.
SEAN CARROLL: These are the infamous Tsavo lions, right?
ANTHONY ALLISON: The famous infamous Tsavo lines.
SEAN CARROLL: Around 1950, biologists
didn't know a lot about the details of evolution,
because we didn't know really how heredity worked.
The structure of DNA had not been discovered yet.
Genetic code had not been cracked.
So we know that, while evolution was due to genetic changes,
we didn't know how those genetic changes took place whatsoever.
So there were holes in the whole picture
of the evolutionary process.
And Tony Allison was probably the least likely person
you would imagine who would fill one of the most critical holes.
He grew up far away from the centers of science
in Europe and North America.
He was really interested in natural history,
and he loved the Kenyan wildlife,
and he visited archeological digs
that were going on at the time.
But it was a really circuitous and serendipitous route
that led him to an enormous discovery
in evolutionary biology.
Tony first went to university in South Africa,
where he studied physical anthropology, then
to medical school at Oxford.
He had a deep interest in human origins,
but not so much an ancient stones and bones.
Tony was interested in blood could the common A-B-O blood
types say anything about the evolutionary history
of East African tribal people?
ANTHONY ALLISON: And I actually learned,
just before going out and about, the sickle cell condition.
And nobody really knew the frequencies of sickle cells
in East Africa.
So it was a barren slate, so to speak.
SEAN CARROLL: Blood samples from people carrying the sickle cell
character appear quite normal until oxygen is removed.
Tony learned that adding a chemical agent to the samples
would quickly reduce oxygen and reveal sickle cells,
if they were there.
This gave him an easy test to score blood samples
for the sickle cell character.
ANTHONY ALLISON: What was striking was
that you had high frequencies of people carrying the sickle cell
character in the coast and near Lake Victoria, and really low
frequencies in the high country in between, in Nairobi.
SEAN CARROLL: What could possibly account
for such a striking disparity?
The sickle cell character was understood to be genetic, not
environmental.
Tony had grown up in the dry Kenyan highlands.
But he knew the warm, moist lowlands were a breeding
ground for the anopheles mosquito
that carried the malaria parasite,
plasmodium falciparum.
And it dawned on him.
The places where there was a really high incidence
of sickle cell where there was a really high incidence
of malaria.
Bang.
Now it was a burning question that confronted Tony.
Could sickle cell and malaria be connected?
And if so, how?
It was a radical notion that a genetic disease could somehow
be connected to an infection.
When you went back to Oxford, you
had this idea of a linkage between sickle cell
and malaria, but you hadn't published it.
Did you know it was a big deal?
ANTHONY ALLISON: I was sure it was a big deal.
SEAN CARROLL: You were sure it was a big deal?
ANTHONY ALLISON: Yes.
That's why I wanted not to go off half-cocked.
I wanted to have a really complete story.
SEAN CARROLL: So he decided he had to sit on this idea
until he got a chance to test it properly.
So a key element of the scientific method
is to come up with a hypothesis.
That's great.
But you've got to test it in every way possible to see
whether or not it can hold up to that sort of scrutiny that's
how science moves forward.
ANTHONY ALLISON: Well, the scientific method essentially
means that you address a problem and try to find a solution.
And so you look at children of the appropriate age
and find out whether they are, in fact, protected
against malaria.
And if that's the case, you predict
that you will have high frequencies
of sickle cells only in areas where malaria is endemic.
SEAN CARROLL: He wanted to know that this correlation held not
just in Kenya, but everywhere.
It would be important to look directly
at the incidence of malaria and sickle cell
in as many areas as possible.
So Tony went on a sickle cell safari.
He wanted to gather blood samples
from all over East Africa to really test this correlation.
And now, he was a trained medical doc.
So he had something to offer.
So he would go into the market on market day
and offer to do checkups on children,
and just take a little finger prick or a little heel prick,
a little sample of blood.
The first thing he did was look at the malaria parasite
load in each sample.
Then he tested for the sickle cell character.
He found that children carrying the character
had a lower parasite count, as if they were partially
protected against malaria.
And when he examined the blood of about 5,000 individuals--
a really massive study--
the correlation was really clear--
so clear, in fact, that he could really
draw a map of East Africa and shade
in the areas of high incidence of sickle cell.
And they were superimposed right on top
of the areas of high incidence of malaria.
Bang.
That was it.
The many samples and detailed maps
made it clear there was a connection between sickle cell
and malaria.
But to understand how sickle cell might protect people
from malaria acquired thinking about the genetics
of sickle cell.
What happens is, the genes are lined up on chromosomes,
and one has pairs of them, with the exception of the sex
chromosomes.
And this means that you have two copies.
So the copies can be the same or they can be different.
And if they're the same, they're called homozygous.
And if they're different, they're called heterozygous.
When an individual finds a partner and reproduces,
one of each pair of chromosomes is passed on.
If the parents are both heterozygous,
carrying one sickle cell and one normal gene,
odds are one and four that the child
will be sickle cell homozygous, two in four
that the child will be heterozygous, and one in four
that the child will carry two copies of the normal gene.
In the absence of malaria, there is strong selection
against the sickle cell gene.
However, in a malarial environment,
individuals born with two copies of the sickle cell gene
and those born with two copies of the normal gene
are both at a disadvantage.
One gets sickle cell disease.
The other is most vulnerable to malaria.
Tony's brilliant insight was that those that carried just
one sickle cell gene had an innate resistance to malaria.
Malaria tipped the selective balance
in favor of heterzygotes.
The evolutionary trade-off is that protection from malaria
comes at the cost of more sickle cell disease in the population.
The sickle cell mutation was not the best genetic solution
you might imagine to resist malaria.
That's not how evolution works.
It was the most available--
a simple typo, A to T, in the gene that encodes hemoglobin.
Mistakes are made in the copying of DNA in every generation.
You and I were born with about 40 or 50 mutations that didn't
exist in either of our parents.
It's just part of the nature of copying 3 billion letters
in the process of reproduction.
And when those mistakes arise, a typo arises in the globin gene.
For most of us, that would be a bad thing.
But if you live in a malarial area,
it gives you an edge against the malarial parasite,
so that mutation is retained.
ANTHONY ALLISON: Well, fitness essentially
is a measure of whether a particular gene is
likely to be passed on to the next generation.
And this means that, for that to happen, the individual carrying
that gene has to survive to reproductive age,
and, secondly, has to reproduce.
SEAN CARROLL: Now you had a sense
that you had this explanation that
was general to the prevalence of sickle cell
and its correlation with malaria.
But you didn't quite know the mechanism, right?
ANTHONY ALLISON: That's right.
SEAN CARROLL: So what did you do next?
ANTHONY ALLISON: Well, I have to say,
I leave that part of this story to others.
Because it's quite a complex story.
SEAN CARROLL: A large body of subsequent research
has shown that the sickle cell mutation compromises
the ability of the parasite to reproduce.
Thus, a mutation that creates one genetic disease
can also protect against another disease.
What Tony gave us was a fully worked out example of evolution
by natural selection.
And the amazing thing was, this was in humans.
This is how natural selection was working on humans
in real time in the real world.
Tony's map of East Africa was a stunning achievement.
But he could go further than that.
He knew that there was a high incidence
of sickle cell in southern Europe, in southern India,
and in other parts of Africa.
And it turns out these were all malarial zones as well.
And so his map applied not to just to East Africa,
but that whole part of the world.
MATTHEW HEENEY: When I'm explaining
about the origins of sickle cell disease
and its association with malaria to children or their families,
they often look at me with incredulity.
They don't understand.
Like, you're kidding, right?
This is all to do with a mosquito infection?
As our species has been able to move across the globe
to areas with low malarial incidents,
this gene is now really more of a nuisance than anything else.
It's not really a clear selective advantage for them
in Boston, let's say.
But it takes thousands of years for the population to change
and for genetics to change based on the pressures around them
in the environment.
SEAN CARROLL: What Tony Allison did,
first with his sharp intuition and then
with his rigorous research, will stand as a monument,
bringing our own evolutionary process into the light.
[MUSIC PLAYING]