Your Inner Fish: A Journey Into the 3.5-Billion-Year History of the Human Body by Neil Shubin Page B

Even more relevant, what could we learn about ourselves from all this?
    Chickens, as Saunders, Zwilling, and Tabin showed, are a surprisingly good proxy for our own limbs. Everything that was discovered by Saunders and Zwilling’s cutting and grafting experiments and by Tabin’s DNA work applies to our own limbs as well: we have a ZPA, we have Sonic hedgehog, and both have a great bearing on our well-being. As we saw, a malfunctioning ZPA or a mutation in Sonic hedgehog can cause major malformations in human hands.
    Randy wanted to determine how different the apparatus is that builds our hands. How deep is our connection to the rest of life? Is the recipe that builds our hands new, or does it, too, have deep roots in other creatures? If so, how deep?
    Sharks and their relatives are the earliest creatures that have fins with a skeleton inside. Ideally, to answer Randy’s question, you would want to bring a 400-million-year-old shark fossil into the laboratory, grind it up, and look at its genetic structure. Then you’d try to manipulate its fossil embryos to learn whether Sonic hedgehog is active in the same general place as in our limbs today. This would be a wonderful experiment, but it is impossible. We cannot extract DNA from fossils so old, and, even if we could, we could never find embryos of those fossil animals on which to do experiments.
    Living sharks and their relatives are the next best thing. Nobody would ever confuse a shark fin with a human hand: you couldn’t ask for two more different kinds of appendages. Not only are sharks and humans very distantly related, but also the skeletal structures of their appendages look nothing alike. Nothing even remotely similar to Owen’s one bone–two bones–lotsa blobs–digits pattern is inside a shark’s fin. Instead, the bones inside are shaped like rods, long and short, thin and wide. We call them bones even though they are made of cartilage (sharks and skates are known as cartilaginous fish, because their skeletons never turn into hard bone). If you want to assess whether Sonic hedgehog ’s role in limbs is unique to limbed animals, why not choose a species utterly different in almost every way? In addition, why not choose the species that is the most primitive living fish with any kind of paired appendage, whether fin or limb? Sharks fit both bills perfectly.
    Our first problem was a simple one. We needed a reliable source for the embryos of sharks and skates. Sharks proved difficult to obtain with any degree of regularity, but skates, their close relatives, were another matter. So we started with sharks and used skates as our supply of sharks dwindled. We found a supplier who would ship us every month or two a batch of twenty or thirty egg cases with embryos inside. We became a virtual cargo cult as we waited each month for our shipment of precious egg cases.
    Work by Tabin’s group and others gave Randy important clues to begin his search. Since Tabin’s work in 1993, people had found Sonic hedgehog in a number of different species, everything from fish to humans. With the knowledge of the structure of the gene, Randy was able to search all the DNA of the skate and shark for Sonic hedgehog . In a very short time he found it: a shark Sonic hedgehog gene.
    The key questions to answer were Where is Sonic hedgehog active?, and, even more important, What is it doing?
    The egg cases were put to use as Randy visualized where and when Sonic hedgehog is active in the development of skates. He first studied whether Sonic hedgehog turns on at the same time in skate fin development as it does in chicken limbs. Yes, it does. Then he studied whether it is turned on in the patch of tissue at the back end of the fin, the equivalent of our pinky. Yes again. Now he did his vitamin A experiment. This was the million-dollar moment. If you treat the limb of a chicken or mammal with this compound, you get a patch of tissue that has Sonic hedgehog activity on the opposite side,