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With a greater understanding of biological mechanisms, humans may be able to take a devastating birth defect and turn it into a treatment for cancer.

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When it comes to mythical one-eyed creatures, the first thing you think of is probably the Cyclops.

There are also lots of other legendary creatures to choose from, too, from the Irish god Balor, who only opens his eye to bring destruction, to the mostly harmless Hitotsume-kozō of Japan. In nature, on the other hand, eyes pretty much always come in twos, and there’s no vertebrate species that evolved to have one eye.

That said, if something goes wrong during its development as an embryo, any vertebrate can develop what’s known as cyclopia, a condition named after those one-eyed creatures of legend. It’s a devastating complication, and generally fatal. But studying it might help researchers discover new ways to treat certain types of cancers.

Most of the reports you’ll find about real cyclopic animals were spread through the internet, but news of cyclops lambs, goats, sharks, and humans is nothing new. There’s even a fairly accurate description of a pig born with cyclopia that dates back to a Connecticut colony in 1642. So how does an animal that normally has two eyes develop only one in the center of its face?

The New Haven colonists claimed that their stillborn piglet was the product of bestiality, but they were wrong … very wrong. It all has to do with how the brain develops. In a developing vertebrate embryo, the brain consists of three regions: the hindbrain, the midbrain, and the forebrain.

The forebrain eventually differentiates into two parts: the diencephalon, which becomes inner parts of the brain like the thalamus and the hypothalamus, and the telencephalon, which turns into the cerebrum. In humans, this happens around week 4 or 5 of gestation. But sometimes, the forebrain doesn’t completely split, which hinders the development of a lot of important brain structures, including the left and right hemispheres.

The condition is called holoprosencephaly, or HPE, and it can vary in severity depending on how much of the brain’s development is affected. Cyclopia is basically the rarest and most severe form of HPE, and it’s named after its most noticeable side effect: a single ocular tract in the center of the face. Embryos also usually develop a proboscis positioned above the eye, and they tend to have other severe physical defects that differ from case to case.

In humans, cyclopia is rare: it’s found in an estimated 1 in 100,000 births, although unfortunately, it’s always fatal. But the less severe forms of HPE are more common. Overall, HPE happens in about 1 in 250 conceptions and 1 in 16,000 live births, and it can be survivable.

Part of the reason HPE is so common is that it can be caused by a lot of different factors, from a single genetic mutation, to an extra copy of a chromosome, to teratogens, which are substances that cause birth defects when a developing embryo is exposed to them. For researchers, learning more about those causes is important because it can help prevent birth defects, but also because they have a lot in common with processes that lead to certain kinds of cancer. The main gene connected with HPE is called Sonic hedgehog, or SHH for short.

It doesn’t actually have anything to do with running really fast, but scientists named it that because there’s a related genetic mutation in fruit flies that makes them look like they’re covered in spines. And because scientists are nerds. The protein SHH codes for, which is also called Shh, plays a crucial role in embryonic development, including telling the forebrain how to differentiate and form hemispheres.

But the Shh protein doesn’t work alone — it’s sort of a delegating boss, telling another protein to instruct a third protein to bind to a cell’s DNA to activate a gene, in what’s known as the Shh signaling pathway. Since there are so many steps involved, there are a lot of ways things can go wrong. If the embryo is exposed to any compound that interrupts this flow of instructions, Shh can’t tell cells in the forebrain to differentiate.

And if the cells don’t know to differentiate, that leads to HPE. Even though SHH is a really important gene in embryos, it’s mostly dormant after birth. But if it gets activated somehow, it can cause uncontrolled cell division that leads to all kinds of cancers — from lung to pancreatic to skin cancer.

In an embryo, interfering with the Shh pathway can be devastating — it’s what leads to HPE. But to treat a cancer that’s caused by the pathway activating when it isn’t supposed to, interfering with it is exactly what you want to do. And in 1968, researchers discovered a compound that obstructs the Shh pathway, thanks to a population of Idaho sheep that kept giving birth to cyclopic lambs.

After more than a decade of research, scientists were able to isolate the responsible compound from the California corn lily. They named it cyclopamine. Pregnant ewes ate the plants while grazing, which caused their offspring to develop all kinds of birth defects.

Lab tests showed that if they ate the cyclopamine on the 14th day of gestation, the lambs developed cyclopia. So now, researchers are trying to take advantage of how cyclopamine disrupts the Shh pathway to save lives. It’s taking a while because cyclopamine is a complicated molecule, and they’ve had a tough time figuring out how to either make or extract enough of it to study it properly.

It’s been even harder to make a version that’s absorbed and used by the body in a way that would make it an effective cancer treatment. But they’re working on it, and versions of cyclopamine and other compounds that disrupt that pathway are being tested against things like pancreatic and skin cancer. So, someday, the story of some lambs and a rare birth defect might save thousands of lives every year.

Thanks for watching this episode of SciShow. If you’re interested in learning more about how cancer works, you can watch our video about why we haven’t cured it yet even though there’s so much time and money being poured into cancer research.