I am amazed at the inventiveness of early researchers in pursuit of the secrets of heredity. With no idea of the true chemistry of genes, investigators designed experiments to reveal genetic facts.
Geneticists of the 1930’s and ‘40’s believed, incorrectly, that genes must be made of protein. Yet during this time, George Beadle made his “one gene—one enzyme” discovery. The discovery came about because Beadle wondered what genes actually do in order to cause traits.
First Beadle investigated fruit fly eye colors. Normal eye color in these flies is a deep-red mixture of red and brown pigments. Two bright-red mutant colors are vermilion and cinnabar; these contain no brown. From mutant larvae, Beadle transplanted vermilion and cinnabar eye discs into normal larvae. The eyes developed normal color in the adult flies. Cross-mutant transplantation showed Beadle that the brown pigment resulted from a series of chemical reactions: a starting substance got changed to vermilion, which got changed to cinnabar, which got changed to brown. Each mutant lacked one of these reactions, but it was time-consuming to figure out which one.
To speed up his investigation, Beadle switched from fruit flies and eye colors, to red bread mold Beadle X-rayed the bread mold to cause mutations, then tested spores from the mold to see if they could grow on a minimal food containing only sugars and salts, and the nutrients it manufactured.
If a mold couldn’t develop on the minimal food, this meant it was missing a nutrient because of a mutation. Beadle tested to see if the mutation was in a single gene. If so, Beadle then added a supplement, such as a vitamin or an amino acid. If that didn’t make the mold grow, he tried a different supplement, until he found the missing nutrient.
During growth, each mutant mold accumulated a chemical. This chemical came from the reaction step where the mutant got stuck. The mutants could be arranged in order, according to where they got stuck, and this order showed the reaction steps in the manufacture of the supplement nutrient.
Beadle knew that each chemical reaction is controlled by an enzyme. So each mutant mold must be missing the enzyme that could change its accumulated chemical to the next one in the series. Since each mutant was missing a single gene, each of those genes must give rise to a single enzyme. “One gene—one enzyme!”