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As part of a plan to accumulate enough money to pay for further graduate studies, Karle took a position in Albany, New York with the New York State Department of Health, where he developed a method to measure dissolved fluorine levels, a technique that would become a standard for water fluoridation.
Fluoridation has been the subject of many court cases wherein activists have sued municipalities, asserting that their rights to consent to medical treatment and due process are infringed by mandatory water fluoridation.