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In the 1950s, a group of ranchers in Idaho

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were baffled when their sheep gave birth[br]to lambs with a singular deformity.

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Mystified by these cyclops sheep,

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they called in scientists from the U.S.[br]Department of Agriculture to investigate.

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The researchers hypothesized[br]that the pregnant ewes

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had snacked on poisonous [br]birth defect-causing plants.

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They collected the local flora[br]and fed samples to lab rats,

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but struggled to replicate the effect.

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So they decided [br]to directly observe the sheep

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with one scientist even living[br]with the herd for three summers.

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After a decade of trial and error,[br]the scientists finally found the culprit,

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wild corn lilies.

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The lilies contained an active molecule[br]with six connected rings

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that they named cyclopamine[br]in reference to the cyclops sheep.

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They didn't know exactly[br]how cyclopamine caused the defect

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but told ranchers to steer clear.

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It took about four decades before[br]a team of biologists,

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led by Professor Philip Beachy,

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stumbled upon the answer.

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His lab was studying a specific gene[br]found in many species,

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from mice to humans,

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called the hedgehog gene.

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It was named by two scientists, who later[br]shared the Noble Prize for their work,

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who found that mutating [br]this gene in fruit flies

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produced pointy spikes like a hedgehog.

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Beachy and his colleagues performed[br]genetic modifications

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to turn off the hedgehog genes in mice.

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This resulted in severe defects [br]in the development

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of their brains, organs, and eyes

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or, rather, eye.

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Then while perusing a textbook, Beachy [br]came across photos of the cyclops sheep

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and realized what had eluded scientists[br]for four decades.

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Something must have gone awry [br]involving the hedgehog gene.

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Let's take a step back.

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Genes contain instructions that tell[br]cells what to do and when to do it,

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and they communicate their directives[br]using proteins.

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The hedgehog gene itself tells cells[br]to release a so-called hedgehog protein,

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which kicks off a complex [br]series of cellular signals.

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Here's how it works in normal[br]healthy development.

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Hedgehog protein latches on to[br]a protein called patched.

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That inhibits, or holds, patched back,

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allowing another protein called[br]smoothened to freely signal the cells,

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telling them where to go[br]and what kind of tissues to become.

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Cyclopamine, say in the form [br]of a delicious corn lily,

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interrupts this pathway[br]by binding onto smoothened.

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That locks smoothened up so that[br]it's unable to send the signals

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needed to mold the brain [br]into two hemispheres,

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and form fingers or separate eyes.

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So even though the hedgehog[br]protein is still doing its job

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of keeping the way clear for smoothened,

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cyclopamine blocks smoothened[br]from passing along its chemical message.

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That settled the science[br]behind the one-eyed sheep,

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but Beachy and his team [br]caught the glimmer

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of another more beneficial connection.

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They noted that uncontrolled activation[br]of the smoothened protein

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was associated with a human syndrome.

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It's known as Basal Cell Nevus Syndrome,[br]and it predisposes people to certain cancers.

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The scientists proposed

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putting cyclopamine's smoothened [br]binding powers to good use

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as a treatment for these cancers,

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as long as the patient wasn't pregnant.

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Unfortunately, researchers eventually[br]found that cyclopamine

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causes negative side effects,

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and its chemical properties[br]make it difficult to work with.

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But they did discover that closely[br]related molecules are safe and effective,

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and two of these drugs were approved[br]in 2012 and 2015 as skin cancer medicines.

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When those farmers first saw[br]the cyclops sheep,

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they could have chalked it up to[br]a freak genetic mutation and walked away.

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Instead, their decision to investigate[br]turned a mystery into medicine

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showing that sometimes[br]there's more than meets the eye.