T4 bacteriophages infecting E. coli bacterium, illustration. Phages are viruses that infect and replicate within bacteria.

In November 1943, a pivotal experiment conducted by physicist Max Delbrück from Vanderbilt University and biologist Salvador Luria at Indiana University provided strong support for a fundamental aspect of Charles Darwin’s theory of evolution. Their research demonstrated that mutations in bacteria occur spontaneously, rather than as direct responses to environmental pressures, a question that had intrigued scientists since Darwin’s groundbreaking work, “On the Origin of Species,” published in 1859.

The duo’s study introduced the “fluctuation test,” which showcased that mutations arose randomly within bacterial populations. This method became a significant tool in understanding the mechanics of evolution. Prior to their findings, some scientists speculated that interactions between bacteriophages—viruses that infect bacteria—and their bacterial hosts might induce mutations, potentially contradicting Darwinian principles.

Delbrück, who fled Germany due to the Nazi regime, unexpectedly entered the realm of genetics while exploring the relationship between quantum mechanics and biology. He became captivated by the ease of observing bacteriophages that attacked the bacterium Escherichia coli in a laboratory in California. He recalls being astonished by the straightforwardness of his observations: “You could put them on a plate with a lawn of bacteria, and the next morning every virus particle would have eaten a macroscopic 1 mm hole in the lawn,” he later remarked in an oral history.

Luria, an Italian-Jewish doctor who also escaped the Nazis, was intrigued by the potential of phages to explore genetic principles. After their initial meeting at Cold Spring Harbor Laboratory in New York in December 1940, they began to collaborate. Their goal was to test whether phages could induce resistance in E. coli.

The breakthrough moment came when Luria, inspired by a casual conversation with a colleague, realized that statistical analysis could differentiate between random mutations and those induced by phages. They set out to conduct their experiment by filling tubes with E. coli and exposing them to phages while culturing them on plates. If the mutations were acquired, the resistant bacteria would appear in similar proportions across the cultures. Conversely, random mutations would lead to variations in the number of resistant bacteria, resulting in “jackpot plates” with higher counts of resistant E. coli.

Their findings, published in 1943, confirmed that mutations arise randomly, reinforcing the Darwinian hypothesis that natural selection acts upon these variations. This work not only solidified the understanding of bacterial genetics but also laid the groundwork for future research in the field.

Later in 1943, Delbrück and Luria teamed up with microbial chemist Alfred Hershey, who was then at Washington University in St. Louis. Together, they advanced the field of genetics by demonstrating that phages contained multiple genes and could exchange genetic information, a process known as genetic recombination. Their collaborations culminated in the groundbreaking revelation by Hershey and collaborator Martha Chase that DNA serves as the carrier of genetic information.

The contributions from Delbrück, Luria, and Hershey were recognized with the 1969 Nobel Prize in Physiology or Medicine. Their work has had a lasting impact on biology, confirming that natural selection operates on random variations. However, recent studies indicate that not all mutations are purely random. For instance, mutation rates in essential genes may differ from those in less critical ones, suggesting a more complex interplay in genetic variation.

Overall, the experiment by Delbrück and Luria not only confirmed a vital aspect of evolutionary theory but also opened avenues for understanding the mechanisms underlying genetic mutations. Their legacy continues to influence modern genetics and evolutionary biology, illustrating the significance of their findings in the ongoing exploration of life’s fundamental processes.