Both of them have sickle cell anemia.

Before the advent of modern medicine,

sickle cell anemia almost certainly meant death before adulthood.

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.

[DR. HEENEY:] How's it going? Good. Can I see your hands?

This is pretty. Where did that come from? Is that from Brookline?

[NARRATOR:] Besides some bone pain, Skyy leads the fairly normal life

of a 13 year-old girl.

But her younger brother Davaun,

has suffered acute chest syndrome

and has already had his spleen removed.

[DR. HEENEY:] So you don't get any more belly pains? That's good.

[NARRATOR:] Skyy and Davaun's symptoms arise from the fact

that some of their red blood cells become misshapen--

crescents instead of discs--

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 is not rare.

[DR. 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.

[NARRATOR:] In fact, in some populations -- African Americans,

for example -- the incidence is as high as 1 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 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 sixty years ago.

[NARRATOR:] Tony Allison has spent most of his career

as a medical doctor and molecular biologist

in the U.S. and England.

But he grew up in East Africa and he is quick

to recall his formative years in Kenya.

[DR. ALLISON:] 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 and, in Tsavo

and there would be lions roaming around,

so it was really quite exciting.

[DR. CARROLL:] These are the infamous Tsavo lions--

[DR. ALLISON:] The famous-- infamous Tsavo lions--

[DR. 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.

[NARRATOR:] 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

in ancient stones and bones.

Tony was interested in blood.

Could the common ABO blood types say anything

about the evolutionary history of East African tribal people?

[DR. ALLISON:] And I actually learned just before going

out about the sickle cell condition.

Nobody really knew the frequencies

of sickle cells in East Africa.

So it was a barren slate, so to speak.

[NARRATOR:] 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.

[DR. ALLISON:] But what was striking was

that you had high frequencies

of people carrying the sickle cell character in the coast

and near Lake Victoria, and very low frequencies

in the high country in-between, in Nairobi.

[NARRATOR:] 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.

[DR. CARROLL:] And it dawned on him,

the places where there was a really high incidence

of sickle cell was where there was a really high incidence

of malaria.

Bang.

[NARRATOR:] 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.

[DR. CARROLL:] When you went back to Oxford--

you had this idea, the linkage between sickle cell

and malaria, but you hadn't published it?

Did you know it was a big deal?

I mean, did you...

[DR. ALLISON:] I was sure it was a big deal.

Yes. That's why I wanted not to go off half-cocked.

I wanted to have a really complete story

[DR. CARROLL:] So, he decided he had to sit on this idea

until he got a chance to test it properly.

So, and 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.

[DR. ALLISON:] The scientific method essentially means

that you address a problem and try to find a solution.

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.

[DR. CARROLL:] He wanted to know that this correlation held,

not just in Kenya, but everywhere.

[NARRATOR:] 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.

[DR. CARROLL:] 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

to get a little sample of blood.

[NARRATOR:] 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.

[DR. CARROLL:] 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.

[NARRATOR:] 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 required thinking

about the genetics of sickle cell.

[DR. ALLISON:] 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.

[NARRATOR:] 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

in 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 heterozygotes.

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.

[DR. CARROLL:] 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 three 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.

[DR. 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.

[DR. 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?

[DR. ALLISON:] That's right.

[DR. CARROLL:] So what did you do next?

[DR. ALLISON:] Well [laughs] I have to say I left that part

of the story to others, because it's quite a complex story...

[NARRATOR:] 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.