In 1952, Esther and Joshua Lederberg performed an experiment that helped show that many mutations are random, not directed. In this experiment, they capitalized on the ease with which bacteria can be grown and maintained. Bacteria grow into isolated colonies on plates. These colonies can be reproduced from an original plate to new plates by “stamping” the original plate with a cloth and then stamping empty plates with the same cloth. Bacteria from each colony are picked up on the cloth and then deposited on the new plates by the cloth.

Esther and Joshua hypothesized that antibiotic resistant strains of bacteria surviving an application of antibiotics had the resistance before their exposure to the antibiotics, not as a result of the exposure. Their experimental set-up is summarized below:

	1. Bacteria are spread out on a plate, called the “original plate.”
	2. They are allowed to grow into several different colonies.
	3. This layout of colonies is stamped from the original plate onto a new plate that contains the antibiotic penicillin.
	4. Colonies X and Y on the stamped plate survive. They must carry a mutation for penicillin resistance.
	5. The Lederbergs set out to answer the question, “did the colonies on the new plate evolve antibiotic resistance because they were exposed to penicillin?” The answer is no: When the original plate is washed with penicillin, the same colonies (those in position X and Y) live — even though these colonies on the original plate have never encountered penicillin before.

So the penicillin-resistant bacteria were there in the population before they encountered penicillin. They did not evolve resistance in response to exposure to the antibiotic.