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  • [NARRATOR:] Davaun and Skyy 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.

  • 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.

  • [DR. CARROLL:] 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.