Sunday, October 3, 2010

This is a long set-up to a bad pun

As our developmental biology class ramps up after P.Z.’s unfortunate illness, we have begun to read and discuss Sean Carroll’s book Endless Forms Most Beautiful. At the end of the fourth chapter of that book, Carroll writes:
“Francois Jacob has pointed out that all of our explanatory systems, whether mythic, magic, or scientific, share a common principle. They all seek, in the words of physicist Jean Perrin, ‘to explain the complicated visible by some simple invisible.’”
I think that Jacob, a member of the “Indiana Jones society of scientists who fight Nazis”, is likely correct that scientific and religious systems of knowledge attempt to fulfill a similar role. The difference between the two is that science has to provide evidence for the “simple invisible” that it postulates. To do this we must find a way to illuminate the hidden mechanisms that drive our natural world. The experiments that manage to most clearly show these mechanisms are the ones that become famous. The elegance with which finch beaks or a double slit experiment can reveal natural truths is what makes them so compelling.
Carroll recognizes the importance of making invisible mechanisms apparent, and compares it to our ability to visualize gene expression using florescent antibodies or other molecular mechanisms. However I think Carroll sells himself short. Even before there were the means to make pretty pictures of embryos with glowing stripes, we could still visualize the effects of “master genes” such as the hox genes. We did this by making monsters. Although it may be less elegant than the newer molecular tools, one can gain insights into the process of development by fucking up embryos and examining the horribly deformed monsters that result. The second chapter of Carroll’s book is thick with examples of scientists who created monsters to learn about development. Although the experiments may seem slightly macabre, the discoveries that result are often really neat. One of my favorite examples that we’ve discussed thus far is the discovery of the zone of polarizing activity.
While an embryo is developing, how does each cell know where it is in the body? How do pinky cells know to make pinkies, and thumb cells know to make thumbs? Saunders and Gasseling (1968) discovered one clue to this puzzle by creating mutant chicken arms. Birds have lost the digits that would correspond to our thumb and pinky, leaving them with three digits on their limbs. But when these researchers took early embryos (before they developed anything beyond stumpy limb buds) and moved bits of the developing limb around they created some interesting mutants. When they removed the back of a limb bud from one developing chicken and attached it to the front of the limb bud in another, the resulting wing had two hands. The small number of transplanted cells were able to direct the formation of an entirely new hand (see figure).

This finding showed that a small number of cells could inform the surrounding cells about their relative positions. In essence, saying, “I’m making a ring finger, if you are close to me, build a middle finger and if you are far away make a pointer finger” (remember that birds have only three digits per wing). Saunders and Gasseling called the area of cells that organized the rest of the limb the “zone of polarizing activity” or ZPA. The ZPA provides information about its position by expressing the sonic hedgehog gene. This creates a protein that diffuses out to the surrounding cells. If there is a lot of the protein around, a cell knows that it’s close to the ZPA and that it should make the back of a wing. If the protein is scarce, a cell is far from the ZPA and should build the front of a wing. The ability of a small number of cells to organize the development of larger structures through the expression of genes is important throughout development.

After Saunders discovered the ZPA, he left the scientific world and started a restaurant franchise. The tagline was: “Colonel Saunders, the chicken wing that twice as good as the competition!”


  1. Nice post. I just read 'Your inner fish' by Neil Shubin, which spends a considerable amount of pages on the Hox and the Sonic Hedgehog gene. It's an excellent and fun read that really helps you to understand their origin.

  2. I like this post for at least two reasons:

    1) "fuck up"
    2) the pun