Genetics' Next Frontier

In 1974, I published a paper entitled "The genetics of Caenorhabditis elegans ," also known as the nematode. Its first sentence read: "How genes might specify the complex structures found in higher organisms is a major unsolved problem of biology." This remains true today. How do genes build organs, bones, or skin and specify their function? Has our slowness in finding out been due to our difficulties in choosing the right organism to study?

Until the early 1960's, biology's great-unanswered question was far more modest: how does DNA determine the simplest of proteins? But then it became clear that all you have to do is get a gene and sequence it, get a protein and sequence it, and simply translate one into the other. In principle, we could learn what genes do just by reading their chemical language.

Of course we didn't have the right tools at the time. We did have primitive tools to sequence proteins, so we could figure out their chemistry. But we could not tackle the chemistry of genes. All we could do was follow the standard--and painfully slow--procedure established by Gregor Mendel, the 19 th Century founder of genetics. According to Mendel, a gene's presence in an organism is confirmed only when we find an alternative form of it, called an allele . For example, Mendel could not say that there was a gene for tallness in a plant species until he discovered dwarf mutants of the same species.

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