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Maya Pines’s “Learning from the Worm”

Maya Pines’s “Learning from the Worm” is highly informative and well written. In short, the article confronts the mystery behind the mechanisms that operates during cellular development. Scientists were divided over the type of mechanism that is used to determine a cell’s fate, whether the cell would develop into a nerve, muscle, sex, or somatic cells. Two theories surfaced: if whether a cell’s fate is intrinsic or cell-interactive. Some scientists refer to these two theories as European or American plan of development.

The European plan of development pertains to the idea that a cell’s fate is determined by their ancestry whereas the American plan of development, a cell’s fate is determined by outside environment and position. The little round worm known as C. elegans was used as a basis for the experiments. This was an excellent choice because not only did the worm have a short life span, reaching sexual maturity in 3 days, but also because the worm is a hermaphrodite. The fact that the worm was a hermaphrodite proved to be an incredible advantage.

The worm was able to self fertilize; making it possible for mutants that would otherwise die out without breeding to propagate. Also, the worm was transparent which allowed the scientists to view the developments of each individual cell and the role that they play. Thousands of these tiny worms can fit into a petri dish where they can be viewed for recombinations and mutations. An English scientist, John Sulston studied the C. Elegans, using a light microscope equipped with Nomarski contrast optics to trace the worm’s cells as the animal developed, tracing the history of every cell.

Although this was an effective way of studying the worm, other scientists sliced the worm from nose to end, and analyzing the worm under an electron microscope. Through these techniques, scientists have been able to obtain first-time information on the rules of development at the single cell level. This information provides the foundation for future experiments with the worm, trying to determine how a cell’s fate is decided. In experimenting with the reproductive properties of the worm, scientist, Sternberg and Horvitz stumbled across a series of 3 genes, which are related to human cancer.

Using the knowledge that they’ve obtained through experimentation, the scientists set about trying to determine what molecules took part in determining which cells become the vulva tissues and which become skin. They began by distinguishing the mutant worms, which was not a difficult task to undertake. The mutant worms were defective in egg laying because they had no vulva in which to expel the eggs. But because the worms were hermaphrodites, self-fertilization occurred, where the eggs internally developed and hatched within the worm’s body, eventually consuming the parent’s body.

Scientists were able to determine the signal, a protein known as glp-1, for the development of the vulva. Six cells form an equivalence group, and each harbor the potential to become vulva tissues. An anchor cell in the worm’s gonads induces 3 of the cells in the equivalence group to become the vulva tissue whereas the other three become skin. If the anchor cell get knocked out, in other words get destroyed, all six cells become skin rather than the vulva. However, should the anchor cell be moved to another position, it can signal other cells to generate vulva tissues.

Sternberg and Horvitz had worked with two different mutant worms, the vulvaless and the multivulva where they surprisingly found a series of three genes, which were somewhat, related to human cancer. A gene, let-23, which is very similar to the growth factor receptors in human cells and implicated in cancer, codes for a receptor on cell membranes, which binds to growth factors. The gene, in worms, interacts with another protein, setting off a domino affect of interactions that reach to the nucleus. Let-60 codes for this other protein and belongs to the family of ras genes, which is originally found in human tumors.

However, the mutated version of this gene can cause cancer. Before the ras protein was discovered in the worm, scientists had know clue as to what the ras proteins normally does in an organism. The mutation that was identified in human cancer was also identified in worm development. With this new discovery, scientists were able to determine the function of the ras protein, which triggers specific changes in tissues during development. A C. Elegans embryos have highly predictable developments. However, when the gene that tells the cells when to develop are removed or altered, the worms develop goes out of sync.

These mutations: heterochronic, genes that tell a cell its place in the developmental stages and homeotic which were genes that told a cell where its position is in the embryo, signal a gene when to turn on or off. Occasionally, a cell must undergo a programmed cell death, in which cells are programmed to die by the genes. This is necessary, otherwise, organs that are inappropriate may develop. Still, scientists return to the same question that was posed of before, what possible mechanisms control these processes, whether it be cell death or the development of various tissues.

In the final paragraph, Horvitz states “But evolution is a tinkler…. It takes what already exists and adds to it…”. I think it’s an interesting statement and it holds a lot of truth to it as well. Our bodies, as complex as it may be, still retains much of the apparatuses that can be found in other organisms preceeding us and even in the organisms of today. The worm in this case was used as a sort of map into our own mechanisms and through future studies, scientists will be able to finally discover the incredible enigma behind a development of a cell.

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