How did scientists find out that DNA, not protein, carries heredity?

Scientists learned that DNA carries heredity from bacteria that changed type. In 1944 Oswald Avery, Colin MacLeod and Maclyn McCarty reported that DNA is the substance that causes bacterial transformation, when most researchers believed proteins carried genetic information.

The story starts with Frederick Griffith's mice. Until his experiment, bacteriologists thought the types of pneumococcus bacteria were fixed from one generation to the next. Griffith heat-killed a virulent strain and added its remains to a harmless strain. Neither alone harmed the mice, but together they killed them: something in the dead cells had transformed the harmless bacteria.

Avery's team set out to find that something. They killed the bacteria with heat, removed the protein with chloroform and broke down the polysaccharide capsules with an enzyme. What remained had the chemical proportions of DNA. Then came the decisive tests: enzymes that break down proteins or RNA did not touch its transforming power, but a preparation that breaks down DNA destroyed it.

Many biologists still doubted it. Levene's influential hypothesis had DNA as dull repeating units, with genes likely made of protein, and Alfred Mirsky suggested protein contamination was the real cause. The case closed gradually: Rollin Hotchkiss estimated protein contamination at 0.02% at most, and after the 1952 Hershey-Chase experiment it was soon widely accepted that DNA was the genetic material.