Agilent Technologies : and the Mystery of the One-Eyed Sheep

Here is an amazing triple mystery involving one-eyed sheep, Sonic hedgehog and cancer.

In the 1940s, sheep ranchers in southern Idaho faced a mystery: up to 25 percent of baby lambs were suddenly being born with major birth defects. Defects included underdeveloped brains and a single, central eye - like the cyclops of Greek mythology. (Nature's Poisons)

(You can see a photo here, but I warn you: It will give you nightmares.)

U.S. Department of Agriculture scientists spent 11 years unraveling the mystery. It turns out the mother sheep were eating corn lily plants (Veratrum californicum). Corn lily contained a previously unknown poison, which earned the name 'cyclopamine.' This poison did not harm the mothers, but it affected their unborn babies.

This discovery gave rise to a second mystery: Why does cyclopamine cause birth defects?

Fast-forward another 25 years. Scientists discovered that cyclopamine blocks a gene called 'Sonic hedgehog.' (This gene is so-named because when it's faulty, it makes embryos look spiky like a hedgehog.)

Sonic hedgehog is essential for embryonic development - it tells developing cells whether to keep dividing or start specializing. But the gene also plays a role in causing cancers of the pancreas, skin, prostate and esophagus. (Forbes)

Do you see the opportunity here?

• Sonic hedgehog causes cancer.
• Cyclopamine blocks sonic hedgehog.

This connection led Genetech to develop vismodegib, a treatment for basal cell skin cancer.

But the new drug presented medical science with yet a third mystery: One in five basal cell skin cancers becomes resistant to vismodegib. (Science Blog)

Researchers have now discovered why. The answer involves a molecule called Smoothened, which transmits the hedgehog signal into the cell. (Look, I just report the names - I don't make them up.) Faults in Smoothened prevent vismodegib from working properly. Equipment used to resolve this mystery included an Agilent HPLC system.

In separate work, researchers have developed a rapid and efficient method for isolating and purifying large quantities of cyclopamine from the roots and rhizomes of corn lily. This will allow cyclopamine to become more readily available. The researchers used an Agilent HPLC system to analyze cyclopamine samples.

For Research Use Only. Not for use in diagnostic procedures.

Today's blog topic was suggested by my wife. When she talks, I listen. Thanks Gail!

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