[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:07.05,0:00:10.54,Default,,0000,0000,0000,,In the 1950s, a group of ranchers in Idaho
Dialogue: 0,0:00:10.54,0:00:16.40,Default,,0000,0000,0000,,were baffled when their sheep gave birth\Nto lambs with a singular deformity.
Dialogue: 0,0:00:16.40,0:00:18.91,Default,,0000,0000,0000,,Mystified by these cyclops sheep,
Dialogue: 0,0:00:18.91,0:00:23.90,Default,,0000,0000,0000,,they called in scientists from the U.S.\NDepartment of Agriculture to investigate.
Dialogue: 0,0:00:23.90,0:00:27.04,Default,,0000,0000,0000,,The researchers hypothesized\Nthat the pregnant ewes
Dialogue: 0,0:00:27.04,0:00:31.62,Default,,0000,0000,0000,,had snacked on poisonous \Nbirth defect-causing plants.
Dialogue: 0,0:00:31.62,0:00:35.81,Default,,0000,0000,0000,,They collected the local flora\Nand fed samples to lab rats,
Dialogue: 0,0:00:35.81,0:00:38.48,Default,,0000,0000,0000,,but struggled to replicate the effect.
Dialogue: 0,0:00:38.48,0:00:41.39,Default,,0000,0000,0000,,So they decided \Nto directly observe the sheep
Dialogue: 0,0:00:41.39,0:00:45.90,Default,,0000,0000,0000,,with one scientist even living\Nwith the herd for three summers.
Dialogue: 0,0:00:45.90,0:00:50.95,Default,,0000,0000,0000,,After a decade of trial and error,\Nthe scientists finally found the culprit,
Dialogue: 0,0:00:50.95,0:00:53.03,Default,,0000,0000,0000,,wild corn lilies.
Dialogue: 0,0:00:53.03,0:00:57.30,Default,,0000,0000,0000,,The lilies contained an active molecule\Nwith six connected rings
Dialogue: 0,0:00:57.30,0:01:01.91,Default,,0000,0000,0000,,that they named cyclopamine\Nin reference to the cyclops sheep.
Dialogue: 0,0:01:01.91,0:01:06.21,Default,,0000,0000,0000,,They didn't know exactly\Nhow cyclopamine caused the defect
Dialogue: 0,0:01:06.21,0:01:09.03,Default,,0000,0000,0000,,but told ranchers to steer clear.
Dialogue: 0,0:01:09.03,0:01:12.39,Default,,0000,0000,0000,,It took about four decades before\Na team of biologists,
Dialogue: 0,0:01:12.39,0:01:14.61,Default,,0000,0000,0000,,led by Professor Philip Beachy,
Dialogue: 0,0:01:14.61,0:01:16.76,Default,,0000,0000,0000,,stumbled upon the answer.
Dialogue: 0,0:01:16.76,0:01:20.70,Default,,0000,0000,0000,,His lab was studying a specific gene\Nfound in many species,
Dialogue: 0,0:01:20.70,0:01:22.64,Default,,0000,0000,0000,,from mice to humans,
Dialogue: 0,0:01:22.64,0:01:25.12,Default,,0000,0000,0000,,called the hedgehog gene.
Dialogue: 0,0:01:25.12,0:01:30.23,Default,,0000,0000,0000,,It was named by two scientists, who later\Nshared the Noble Prize for their work,
Dialogue: 0,0:01:30.23,0:01:33.50,Default,,0000,0000,0000,,who found that mutating \Nthis gene in fruit flies
Dialogue: 0,0:01:33.50,0:01:37.49,Default,,0000,0000,0000,,produced pointy spikes like a hedgehog.
Dialogue: 0,0:01:37.49,0:01:40.34,Default,,0000,0000,0000,,Beachy and his colleagues performed\Ngenetic modifications
Dialogue: 0,0:01:40.34,0:01:43.47,Default,,0000,0000,0000,,to turn off the hedgehog genes in mice.
Dialogue: 0,0:01:43.47,0:01:46.69,Default,,0000,0000,0000,,This resulted in severe defects \Nin the development
Dialogue: 0,0:01:46.69,0:01:49.75,Default,,0000,0000,0000,,of their brains, organs, and eyes
Dialogue: 0,0:01:49.75,0:01:51.77,Default,,0000,0000,0000,,or, rather, eye.
Dialogue: 0,0:01:51.77,0:01:57.03,Default,,0000,0000,0000,,Then while perusing a textbook, Beachy \Ncame across photos of the cyclops sheep
Dialogue: 0,0:01:57.03,0:02:01.23,Default,,0000,0000,0000,,and realized what had eluded scientists\Nfor four decades.
Dialogue: 0,0:02:01.23,0:02:05.11,Default,,0000,0000,0000,,Something must have gone awry \Ninvolving the hedgehog gene.
Dialogue: 0,0:02:05.11,0:02:06.78,Default,,0000,0000,0000,,Let's take a step back.
Dialogue: 0,0:02:06.78,0:02:12.53,Default,,0000,0000,0000,,Genes contain instructions that tell\Ncells what to do and when to do it,
Dialogue: 0,0:02:12.53,0:02:16.15,Default,,0000,0000,0000,,and they communicate their directives\Nusing proteins.
Dialogue: 0,0:02:16.15,0:02:21.69,Default,,0000,0000,0000,,The hedgehog gene itself tells cells\Nto release a so-called hedgehog protein,
Dialogue: 0,0:02:21.69,0:02:26.20,Default,,0000,0000,0000,,which kicks off a complex \Nseries of cellular signals.
Dialogue: 0,0:02:26.20,0:02:29.21,Default,,0000,0000,0000,,Here's how it works in normal\Nhealthy development.
Dialogue: 0,0:02:29.21,0:02:32.61,Default,,0000,0000,0000,,Hedgehog protein latches on to\Na protein called patched.
Dialogue: 0,0:02:32.61,0:02:36.02,Default,,0000,0000,0000,,That inhibits, or holds, patched back,
Dialogue: 0,0:02:36.02,0:02:41.33,Default,,0000,0000,0000,,allowing another protein called\Nsmoothened to freely signal the cells,
Dialogue: 0,0:02:41.33,0:02:45.45,Default,,0000,0000,0000,,telling them where to go\Nand what kind of tissues to become.
Dialogue: 0,0:02:45.45,0:02:49.86,Default,,0000,0000,0000,,Cyclopamine, say in the form \Nof a delicious corn lily,
Dialogue: 0,0:02:49.86,0:02:53.77,Default,,0000,0000,0000,,interrupts this pathway\Nby binding onto smoothened.
Dialogue: 0,0:02:53.77,0:02:57.62,Default,,0000,0000,0000,,That locks smoothened up so that\Nit's unable to send the signals
Dialogue: 0,0:02:57.62,0:03:00.92,Default,,0000,0000,0000,,needed to mold the brain \Ninto two hemispheres,
Dialogue: 0,0:03:00.92,0:03:04.74,Default,,0000,0000,0000,,and form fingers or separate eyes.
Dialogue: 0,0:03:04.74,0:03:08.13,Default,,0000,0000,0000,,So even though the hedgehog\Nprotein is still doing its job
Dialogue: 0,0:03:08.13,0:03:10.35,Default,,0000,0000,0000,,of keeping the way clear for smoothened,
Dialogue: 0,0:03:10.35,0:03:15.52,Default,,0000,0000,0000,,cyclopamine blocks smoothened\Nfrom passing along its chemical message.
Dialogue: 0,0:03:15.52,0:03:18.21,Default,,0000,0000,0000,,That settled the science\Nbehind the one-eyed sheep,
Dialogue: 0,0:03:18.21,0:03:20.41,Default,,0000,0000,0000,,but Beachy and his team \Ncaught the glimmer
Dialogue: 0,0:03:20.41,0:03:23.50,Default,,0000,0000,0000,,of another more beneficial connection.
Dialogue: 0,0:03:23.50,0:03:27.12,Default,,0000,0000,0000,,They noted that uncontrolled activation\Nof the smoothened protein
Dialogue: 0,0:03:27.12,0:03:29.88,Default,,0000,0000,0000,,was associated with a human syndrome.
Dialogue: 0,0:03:29.88,0:03:36.17,Default,,0000,0000,0000,,It's known as Basal Cell Nevus Syndrome,\Nand it predisposes people to certain cancers.
Dialogue: 0,0:03:36.17,0:03:37.100,Default,,0000,0000,0000,,The scientists proposed
Dialogue: 0,0:03:37.100,0:03:42.47,Default,,0000,0000,0000,,putting cyclopamine's smoothened \Nbinding powers to good use
Dialogue: 0,0:03:42.47,0:03:44.45,Default,,0000,0000,0000,,as a treatment for these cancers,
Dialogue: 0,0:03:44.45,0:03:47.18,Default,,0000,0000,0000,,as long as the patient wasn't pregnant.
Dialogue: 0,0:03:47.18,0:03:50.70,Default,,0000,0000,0000,,Unfortunately, researchers eventually\Nfound that cyclopamine
Dialogue: 0,0:03:50.70,0:03:52.42,Default,,0000,0000,0000,,causes negative side effects,
Dialogue: 0,0:03:52.42,0:03:56.14,Default,,0000,0000,0000,,and its chemical properties\Nmake it difficult to work with.
Dialogue: 0,0:03:56.14,0:04:00.100,Default,,0000,0000,0000,,But they did discover that closely\Nrelated molecules are safe and effective,
Dialogue: 0,0:04:00.100,0:04:07.71,Default,,0000,0000,0000,,and two of these drugs were approved\Nin 2012 and 2015 as skin cancer medicines.
Dialogue: 0,0:04:07.71,0:04:10.38,Default,,0000,0000,0000,,When those farmers first saw\Nthe cyclops sheep,
Dialogue: 0,0:04:10.38,0:04:14.59,Default,,0000,0000,0000,,they could have chalked it up to\Na freak genetic mutation and walked away.
Dialogue: 0,0:04:14.59,0:04:19.58,Default,,0000,0000,0000,,Instead, their decision to investigate\Nturned a mystery into medicine
Dialogue: 0,0:04:19.58,0:04:23.43,Default,,0000,0000,0000,,showing that sometimes\Nthere's more than meets the eye.