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The Lederberg Experiment

In 1952, Esther and Joshua Lederberg performed an experiment that helped to show that many mutations are random, not directed.

Here is the experimental set-up for the Lederberg experiment. All you really need to know in terms of background information is that bacteria grow into isolated colonies on plates, and that you can reproduce the colonies 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.

The hypothesis for the experiment is 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.

Bacteria are innoculated 1. Bacteria are spread out on a plate, called the “original plate.”
Bacteria grow into colonies 2. They are allowed to grow into several different colonies.
Bacterial copy exposed to penicillin 3. This layout of colonies is stamped from the original plate onto a new plate that contains the antibiotic penicillin.
Survivors 4. Colonies X and Y on the stamped plate survive. They must carry a mutation for penicillin resistance.
Survivors on the original plate

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.

Explore further
Mutations are random

Teach this!
Lesson plans for teaching about the evolution of antibiotic resistance

Next Topic:
Causes of Mutations

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Spanish translation of Understanding Evolution For Teachers from the Spanish Society of Evolutionary Biology.