The Hollywood Approach

It’s easy to see that education is a vital component of antimicrobial stewardship. The better professionals, patients and the public understand how resistance evolves and how their own behaviors can contribute, the more likely they are to bring about change. But what’s the best way to educate? Researchers from the Kishony laboratory at Harvard Medical School and the Technion – Israel Institute of Technology think it’s through visual aids – and they’ve undertaken a big project to help.

What exactly is a “big project?” In this case, it’s MEGA (the Microbial Evolution and Growth Arena) – a 2’x4’ Petri dish that took 14 liters of agar to fill. The dish was divided into nine sections with increasing doses of antibiotic, then seeded with Escherichia coli and filmed continuously in time-lapse for two weeks. The result was a fascinating visualization of the way bacteria move through space – and the speed at which they can evolve resistance to even the highest concentrations of antibiotics.

Roy Kishony: Much of the credit for the idea isn’t ours – it’s all thanks to Hollywood! I was inspired by a video of a gigantic Petri dish billboard made as an ad for a movie, and thought it would be cool if we could use an experiment like that to demonstrate evolution. Tami Lieberman, a doctoral student in my lab, came up with the idea of patterning the plate with increasing concentrations of antibiotic to challenge the bacteria to evolve. And Michael made it all happen!

Michael Baym: It was really a joy to work with such a talented team. The idea of making movies of evolution actually happening was really compelling, and when we saw them, we realized that we could not only use this as a teaching tool, but could learn new things about the process itself.

One thing we learned is that small difficulties that aren’t a big deal in a small experiment can become hugely important in a large one. We had enormous difficulties with condensation, contamination, temperature control, and even being able to see the bacteria. Once, yeast managed to get into our plate – and since it was unaffected by the antibiotics, it took over the whole plate shockingly fast.

RK: We also found that it’s not always the “fittest,” or most resistant, mutations that expand fastest into higher antibiotic concentrations. Just like we know from our own lives, bacteria too can have trade-offs – doing one thing well can mean doing other things less perfectly.

Watch the video here

MB: They can also just be unlucky. Bacteria don’t just need the right mutation; they have to have it in the right place at the right time. Evolution doesn’t always select the very best. Sometimes, it’s just those that are “good enough” and get there first.

RK: Eventually, we hope that by systematically mapping the mutations that lead to resistance to a range of antibiotics, we will be able to develop a new paradigm of “anticipatory diagnostics.” Based on a pathogen’s genome, we’ll be able to tell doctors which antibiotics to use and even which specific combinations to use to best limit the chance of evolution.

It’s no secret that antibiotic resistance is growing as a major public health concern. If we don’t do anything about it, we may be facing a “post-antibiotic era” in which common infections and minor injuries can kill. So we need to make changes – like reducing antibiotic use and misuse. We also need to rethink the paradigm of antibiotic treatment and come up with new ways of combining drugs in order to slow down, and perhaps even reverse, the acquisition of resistance.

It makes us very happy that our videos can be used to help explain and visualize otherwise vague concepts of evolution, like mutations, selection and gradual adaptation – and we were humbled to learn that our video was chosen to be shown in the United Nations event on antibiotics. Both Michael and I were invited to the event, and seeing our work used to make a difference in international public policy-making was a highly rewarding experience!