Cyclopamine (11-deoxojervine) is a naturally occurring chemical that belongs in the family of steroidal alkaloids. It is a teratogen isolated from the corn lily (Veratrum californicum) that causes fatal birth defects. It prevents the embryonic brain from separating into two lobes (an extreme form of holoprosencephaly), which in turn causes the development of a single eye (cyclopia). The chemical was named after this effect, as it was originally noted by Idaho lamb farmers who contacted the US Department of Agriculture after their herds gave birth to cycloptic lambs in 1957. It then took more than a decade to identify the corn lily as the culprit. Later work suggested that different rain patterns caused the sheep to graze differently, impacting the amount of corn lily ingested by pregnant sheep. The poison interrupts the sonic hedgehog signaling pathway during development, thus causing birth defects. Discovery and naming In 1957, Idaho sheep ranchers contacted the US Department of Agriculture (USDA) when their sheep gave birth to lambs with a fatal singular eye deformity. After collecting local flora and feeding them to mice, USDA scientists struggled to recreate the cyclopia. After a decade of trial and error, they came across wild corn lilies and advised the ranchers to avoid the corn lilies. Cyclopamine was one of three steroidal alkaloids isolated from Veratrum californicum, known also as the California corn lily, but the only unknown at the time, and it was named after its effects on sheep embryos. Four decades later a team led by Professor Phillip Beachy related the sonic hedgehog gene to cyclopamine. Upon experimentation, they recreated cyclopia by silencing the sonic hedgehog gene. Professor Beachy then connected their cycloptic results to the cycloptic sheep noted four decades earlier. Source and structure The biosynthesis of cyclopamine begins with cholesterol. A steroid skeleton has a classic 6-member ring, adjacent to another 6, 6, then a five or "6-6-6-5". Veratrum was determined to contain five types of alkaloids, each of which had a common cholesterol precursor: (1) solanidine alkaloids, (2) verazine alkaloids, (3) vertramine alkaloids, (4) jervine alkaloids, and (5) the cevanine alkaloids. In biosynthesis, Cyclopamine has a solanide (1) precursor, which itself is made from cholesterol. This was determined by initial studies which isolated alkaloids from corn lily (Veratrum californium), and introduced these to embryonic sheep. At the time, jervine was an already known alkaloid which was isolated from corn lily alongside two other