What shape are your cells?

Squishy cylinders? Jagged zig-zags?

You probably don’t think much about

the bodies of these building blocks,

but at the microscopic level, small

changes can have huge consequences.

And while some adaptations change

these shapes for the better,

others can spark a cascade of

debilitating complications.

This is the story of sickle-cell disease.

Sickle-cell disease affects the

red blood cells,

which transport oxygen from the lungs

to all the tissues in the body.

To perform this vital task,

red blood cells are filled with hemoglobin

proteins to carry oxygen molecules.

These proteins float independently

inside the red blood cell’s pliable,

doughnut-like shape,

keeping the cells flexible enough

to accommodate even the

tiniest of blood vessels.

But in sickle cell disease,

a single genetic mutation alters

the structure of hemoglobin.

After releasing oxygen to tissues,

these mutated proteins lock

together into rigid rows.

Rods of hemoglobin cause the cell

to deform into a long, pointed sickle.

These red blood cells are

harder and stickier,

and no longer flow smoothly through

blood vessels.
Sickled cells snag and pile up–

sometimes blocking the vessel completely.

This keeps oxygen from reaching

a variety of cells,

causing the wide range of symptoms

experienced by people
with sickle-cell disease.

Starting when they’re

less than a year old,

patients suffer from repeated episodes of

stabbing pain in oxygen-starved tissues.

The location of the clogged vessel

determines the specific

symptoms experienced.

A blockage in the spleen,

part of the immune system,

puts patients at risk for

dangerous infections.

A pileup in the lungs can produce

fevers and difficulty breathing.

A clog near the eye can cause vision

problems and retinal detachment.

And if the obstructed vessels

supply the brain

the patient could even

suffer a stroke.

Worse still, sickled red blood cells

also don’t survive very long—

just 10 or 20 days, versus a

healthy cell’s 4 months.

This short lifespan

means that patients live with a constantly

depleted supply of red blood cells;

a condition called sickle-cell anemia.

Perhaps what’s most surprising

about this malignant mutation
is that it originally evolved
as a beneficial adaptation.

Researchers have been able to trace

the origins of the sickle cell mutation

to regions historically ravaged

by a tropical disease called malaria.

Spread by a parasite found

in local mosquitoes,

malaria uses red blood cells as incubators

to spread quickly and lethally

through the bloodstream.

However, the same structural changes

that turn red blood cells into roadblocks

also make them more resistant to malaria.

And if a child inherits a copy of the

mutation from only one parent,

there will be just enough abnormal

hemoglobin

to make life difficult for the

malaria parasite,

while most of their red blood cells retain

their normal shape and function.

In regions rife with this parasite,

sickle cell mutation offered a serious

evolutionary advantage.

But as the adaptation flourished,

it became clear that inheriting the

mutation from both parents

resulted in sickle-cell anemia.

Today, most people with

sickle-cell disease

can trace their ancestry to a country

where malaria is endemic.

And this mutation still plays a key role

in Africa,

where more than 90% of malaria

infections occur worldwide.

Fortunately, as this “adaptation” thrives,

our treatment for sickle cell continues

to improve.

For years, hydroxyurea was the only

medication available

to reduce the amount of sickling,

blunting symptoms and

increasing life expectancy.

Bone marrow transplantations

offer a curative measure,

but these procedures are

complicated and often inaccessible.

But promising new medications

are intervening in novel ways,

like keeping oxygen bonded to

hemoglobin to prevent sickling,

or reducing the stickiness

of sickled cells.

And the ability to edit DNA

has raised the possibility of enabling

stem cells to produce normal hemoglobin.

As these tools become available

in the areas most affected by malaria

and sickle cell disease,

we can improve the quality of life

for more patients with this

adverse adaptation.