Bacteria Can Develop Resistance to Drugs They Haven’t Encountered Before: Scientists Figured This Out Decades Ago in a Classic Experiment
Do bacteria mutate randomly, or do they mutate for a purpose? This question has puzzled researchers for over a century. In 1943, microbiologist Salvador Luria and physicist turned biologist Max Delbrück conducted an experiment that shed light on this conundrum. Their findings not only won them the Nobel Prize in physiology or medicine in 1969 but also continue to be taught in biology classrooms today. The experiment, known as the Luria-Delbrück experiment, demonstrated that bacteria can develop resistance to antibiotics they haven’t encountered before.
The experiment involved a test tube containing bacteria living in nutrient broth. When a virus that infects bacteria, known as a phage, was added to the tube, it killed most of the bacteria and made the broth clear. However, over time, the broth would become cloudy again, indicating that the bacteria had developed resistance against the phages and were able to proliferate.
Scientists had different theories about the role of phages in this change. Some believed that phages incited the bacteria to mutate for survival, while others argued that bacteria mutated randomly, and the development of phage-resistant variants was simply a lucky outcome. Luria and Delbrück had been working together for months to solve this mystery but had not been successful.
Then, on the night of January 16, 1943, Luria had a eureka moment while watching a colleague hit the jackpot at a slot machine. The next morning, he rushed to his lab to conduct a new experiment. Luria’s experiment involved tubes filled with nutrient broth and dishes coated with phages. Bacteria were placed in the tubes and given two opportunities to generate phage-resistant variants: they could mutate in the absence of phages in the tubes or mutate in the presence of phages in the dishes.
The next day, Luria transferred the bacteria from each tube into a dish filled with phages. The day after that, he counted the number of resistant bacterial colonies in each dish. If bacteria developed resistance against phages by interacting with them, none of the bacteria in the tubes should have mutations. However, if bacteria developed resistance independently of interacting with phages, some of the bacteria in the tubes would have mutations.
The results of Luria’s experiment showed a pattern similar to that of slot machine cash-outs. Most dishes contained no or small numbers of mutant colonies, but several dishes contained a large number of mutant colonies, which Luria considered jackpots. This indicated that the bacteria had developed resistant variants before they even encountered the phages in the dishes.
The significance of the Luria-Delbrück experiment extends beyond their findings. Their experiment paved the way for further research in the field of bacterial resistance. Other scientists conducted similar experiments, replacing phages with antibiotics such as penicillin and tuberculosis drugs. These experiments yielded similar results, showing that bacteria did not need to encounter an antibiotic to acquire resistance to it.
The implications of this experiment are profound. Bacteria have relied on random mutations to survive in harsh and constantly changing environments for millions of years. Their ability to develop resistance to antibiotics they haven’t encountered before suggests that drug resistance is an inevitable reality. As Professor Qi Zheng, a biostatistician at Texas A&M University, states, “Drug resistance is a reality of life we will have to accept and continue to fight against.”
The Luria-Delbrück experiment serves as a reminder that bacteria are constantly evolving and adapting. It highlights the importance of ongoing research and innovation in the field of antibiotics to stay one step ahead of bacterial resistance. While the experiment was conducted decades ago, its lessons remain relevant today and provide valuable insights into the future of antibiotic development and usage.
