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Christiane Nüsslein-Volhard
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Christiane Nüsslein-Volhard

Christiane Nüsslein-Volhard and Eric Wieschaus are two geneticists who introduced "Big Science" into biology, by conducting a spectacularly successful large-scale mutagenesis project that illuminated the embryonic development program of the fruit fly (Drosophila melanogaster).

Molecular biology is traditionally the province of small labs and jujitsu-like experiments that demonstrate principles or examples of possibly general significance. Experiments that demonstrate the activity of one gene, or the action of one protein, are the norm. On the other hand, surveys of large swaths of biological complexity are relatively rare, though very much in the news lately due to the human genome sequencing project. But occasional geneticists such as Nüsslein-Volhard and Wieschaus or Leland Hartwell have been more ambitious, developing collections of mutant organisms that serve to fund the investigation of whole processes and sometimes the work of many investigators.

Fruit flies have long been a workhorse of genetics due to their small size, quick generation time, complex body plan. The rich set of tools and pre-existing knowledge in the field continues to fertilize further work. What Nüsslein-Volhard and Wieschaus did was to randomly generate mutations in single genes and keep those representatives whose descendants showed lethal effects during embryonic development (i.e. birth defects in flies).

They developed a vast collection of malformed and misshapen (not to mention dead) mutants, many with descriptive names like hedgehog, gurken, and krüppel. The subsequent study of these mutants and their interactions led to important new insights into early drosophila development, especially the mechanisms that underly the step-wise development of body segments, an issue that has directly influenced studies of mammalian segmention, which, while less obvious, is just as central to our development and is still evident in our spinal column.