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  • In the 1950s, a group of ranchers in Idaho

  • were baffled when their sheep gave birth to lambs with a singular deformity.

  • Mystified by these cyclops sheep,

  • they called in scientists from the U.S. Department of Agriculture to investigate.

  • The researchers hypothesized that the pregnant ewes

  • had snacked on poisonous birth defect-causing plants.

  • They collected the local flora and fed samples to lab rats,

  • but struggled to replicate the effect.

  • So they decided to directly observe the sheep

  • with one scientist even living with the herd for three summers.

  • After a decade of trial and error, the scientists finally found the culprit,

  • wild corn lilies.

  • The lilies contained an active molecule with six connected rings

  • that they named cyclopamine in reference to the cyclops sheep.

  • They didn't know exactly how cyclopamine caused the defect

  • but told ranchers to steer clear.

  • It took about four decades before a team of biologists,

  • led by Professor Philip Beachy,

  • stumbled upon the answer.

  • His lab was studying a specific gene found in many species,

  • from mice to humans,

  • called the hedgehog gene.

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

  • who found that mutating this gene in fruit flies

  • produced pointy spikes like a hedgehog.

  • Beachy and his colleagues performed genetic modifications

  • to turn off the hedgehog genes in mice.

  • This resulted in severe defects in the development

  • of their brains, organs, and eyes

  • or, rather, eye.

  • Then while perusing a textbook, Beachy came across photos of the cyclops sheep

  • and realized what had eluded scientists for four decades.

  • Something must have gone awry involving the hedgehog gene.

  • Let's take a step back.

  • Genes contain instructions that tell cells what to do and when to do it,

  • and they communicate their directives using proteins.

  • The hedgehog gene itself tells cells to release a so-called hedgehog protein,

  • which kicks off a complex series of cellular signals.

  • Here's how it works in normal healthy development.

  • Hedgehog protein latches on to a protein called patched.

  • That inhibits, or holds, patched back,

  • allowing another protein called smoothened to freely signal the cells,

  • telling them where to go and what kind of tissues to become.

  • Cyclopamine, say in the form of a delicious corn lily,

  • interrupts this pathway by binding onto smoothened.

  • That locks smoothened up so that it's unable to send the signals

  • needed to mold the brain into two hemispheres,

  • and form fingers or separate eyes.

  • So even though the hedgehog protein is still doing its job

  • of keeping the way clear for smoothened,

  • cyclopamine blocks smoothened from passing along its chemical message.

  • That settled the science behind the one-eyed sheep,

  • but Beachy and his team caught the glimmer

  • of another more beneficial connection.

  • They noted that uncontrolled activation of the smoothened protein

  • was associated with a human syndrome.

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

  • The scientists proposed

  • putting cyclopamine's smoothened binding powers to good use

  • as a treatment for these cancers,

  • as long as the patient wasn't pregnant.

  • Unfortunately, researchers eventually found that cyclopamine

  • causes negative side effects,

  • and its chemical properties make it difficult to work with.

  • But they did discover that closely related molecules are safe and effective,

  • and two of these drugs were approved in 2012 and 2015 as skin cancer medicines.

  • When those farmers first saw the cyclops sheep,

  • they could have chalked it up to a freak genetic mutation and walked away.

  • Instead, their decision to investigate turned a mystery into medicine

  • showing that sometimes there's more than meets the eye.

In the 1950s, a group of ranchers in Idaho


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TED-ED】サイクロプス羊の奇妙な事件 - ティエン・グエン (【TED-Ed】The strange case of the cyclops sheep - Tien Nguyen)

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    osmend に公開 2021 年 01 月 14 日