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Why I Do Science: John Casida

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With nearly half a century of pioneering research behind him, the work of renowned insect biochemist and toxicologist John Casida is beyond categorization. He has trained generations of scientists, and his work has led to the design of safer pesticides and more active, less persistent insecticides that play critical roles in modern agriculture.

I find that crossword and jigsaw puzzles are not so much fun because you know there is a solution. But try a mechanism study on a chemical that works on a totally unknown target—now you can really have fun. It may be easy, or it may take 50 years before the background science is available. Alternatively, the new chemical and novel mode of action serves as a probe to dissect a new area of science.

Pesticides—chemicals that affect the growth or survival of a pest—are particularly intriguing. Hundreds of thousands of compounds are sifted every year in the search for very unusual effects, which are great fun to sort out. Each new discovery, advance, or stage of understanding carries with it the thrill of the moment, but they are really for all time as they become part of our knowledge base and toolkit.

The approach of our laboratory is to take a new compound and optimize its potency—meaning that you can use less of it because it is designed to go to just the right place to do the assigned job. When other strategies fail, we use tritium to make the compound highly radioactive and then use this radioligand to quantitate, assay, purify, isolate, and ultimately identify the target. Genomics, proteomics, and all the other “omics” really help us solve problems as never before.

Once you identify the mechanism, you can manipulate a life process. Can you create a useful new pesticide, a new cancer drug, or a new way to measure and modulate a receptor in the brain? Then the challenge is to find a way to use the chemical without side effects while fitting the economic reality of the marketplace. We leave that to the entrepreneurs.

-John Casida

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