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The strange case of the cyclops sheep - Tien Nguyen
The strange case of the cyclops sheep - Tien Nguyen
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0:06
In the 1950s, a group of ranchers in Idaho
0:10
were baffled when their sheep gave birth to lambs with a singular deformity.
0:16
Mystified by these cyclops sheep,
0:18
they called in scientists from the US Department of Agriculture to investigate.
0:23
The researchers hypothesized that the pregnant ewes
0:27
had snacked on poisonous birth defect-causing plants.
0:31
They collected the local flora and fed samples to lab rats,
0:35
but struggled to replicate the effect.
0:38
So they decided to directly observe the sheep
0:41
with one scientist even living with the herd for three summers.
0:45
After a decade of trial and error, the scientists finally found the culprit:
0:50
wild corn lilies.
0:52
The lilies contained an active molecule with six connected rings
0:57
that they named cyclopamine in reference to the cyclops sheep.
1:02
They didn't know exactly how cyclopamine caused the defect
1:05
but told ranchers to steer clear.
1:08
It took about four decades before a team of biologists,
1:12
led by Professor Philip Beachy,
1:14
stumbled upon the answer.
1:16
His lab was studying a specific gene found in many species,
1:20
from mice to humans,
1:22
called the hedgehog gene.
1:24
It was named by two scientists, who later shared the Noble Prize for their work,
1:29
who found that mutating this gene in fruit flies
1:33
produced pointy spikes like a hedgehog.
1:36
Beachy and his colleagues performed genetic modifications
1:40
to turn off the hedgehog genes in mice.
1:43
This resulted in severe defects in the development
1:46
of their brains, organs, and eyes—
1:49
or, rather, eye.
1:51
Then while perusing a textbook, Beachy came across photos of the cyclops sheep
1:56
and realized what had eluded scientists for four decades.
2:00
Something must have gone awry involving the hedgehog gene.
2:05
Let's take a step back.
2:06
Genes contain instructions that tell cells what to do and when to do it,
2:12
and they communicate their directives using proteins.
2:16
The hedgehog gene itself tells cells to release a so-called hedgehog protein,
2:21
which kicks off a complex series of cellular signals.
2:25
Here’s how it works in normal healthy development.
2:28
Hedgehog protein latches on to a protein called patched.
2:32
That inhibits, or holds, patched back,
2:35
allowing another protein called smoothened to freely signal the cells,
2:41
telling them where to go and what kind of tissues to become.
2:45
Cyclopamine, say in the form of a delicious corn lily,
2:49
interrupts this pathway by binding onto smoothened.
2:53
That locks smoothened up so that it's unable to send the signals
2:57
needed to mold the brain into two hemispheres,
3:00
and form fingers or separate eyes.
3:04
So even though the hedgehog protein is still doing its job
3:07
of keeping the way clear for smoothened,
3:10
cyclopamine blocks smoothened from passing along its chemical message.
3:15
That settled the science behind the one-eyed sheep,
3:18
but Beachy and his team caught the glimmer
3:20
of another more beneficial connection.
3:23
They noted that uncontrolled activation of the smoothened protein
3:27
was associated with a human syndrome.
3:29
It's known as Basal Cell Nevus Syndrome,
3:32
and it predisposes people to certain cancers.
3:36
The scientists proposed
3:38
putting cyclopamine's smoothened binding powers to good use
3:42
as a treatment for these cancers,
3:44
as long as the patient wasn't pregnant.
3:46
Unfortunately, researchers eventually found that cyclopamine
3:50
causes negative side effects,
3:52
and its chemical properties make it difficult to work with.
3:55
But they did discover that closely related molecules are safe and effective,
4:01
and two of these drugs were approved in 2012 and 2015 as skin cancer medicines.
4:07
When those farmers first saw the cyclops sheep,
4:10
they could have chalked it up to a freak genetic mutation and walked away.
4:14
Instead, their decision to investigate turned a mystery into medicine
4:19
showing that sometimes there's more than meets the eye.
