Baym and Lieberman worked evenings and weekends. “It was a secret side project and then suddenly we realised there was something to it,” he recalls. “At a department retreat, we showed the first movie where we saw clear patterns of evolution. I then got an email saying: You need to stop everything you’re doing and focus on this.”
The MEGA-plate shows just how easily and readily bacteria can flout our medicines. On its first try, the common gut microbe E. coli evolved to be 1,000 times more resistant to seven very different antibiotics. It became 10,000 times more resistant to trimethoprim, and 100,000 times more resistant to ciprofloxacin. Some strains could even yank the ciprofloxacin out of solution, wearing crystals of the supposedly lethal chemical like little hats.
Other scientists have shown this before, albeit not quite in such a beautiful and intuitive way. But the MEGA-plate isn’t just a fancy visual aide. It’s also a valuable research tool. Baym and his colleagues can collect microbes from different places on the plate and sequence their DNA. They can then reconstruct the gradual accumulation of mutations that allowed some bacteria to make it all the way from the safe periphery to the deadly centre. They can work out which mutations matter.
Most importantly, they can look at how bacteria evolve in realistic three-dimensional spaces. “It is very exciting and takes us much closer to the real thing,” says Pamela Yeh from the University of California, Los Angeles.
Here’s an example. Resistance doesn’t come for free, and the same mutations that make bacteria invincible tend to slow their growth. You can see that in the movie below: at the 0:30 mark, the bacteria have advanced into the first antibiotic zone, but their colonies are faint and sparse.
But as the movie continues, bright spots start appearing within the faint areas. These are bacteria that have picked up “compensatory mutations”, which allow them to grow quickly and resist antibiotics. They ought to have been the fittest microbes on the plate, able to colonise new areas more effectively than their slower-growing peers. But more often than not, they became trapped. Weaker strains at the front of the expanding wave of microbes were already gobbling up all the nutrients, leaving their faster-growing peers with nowhere to grow. “You don’t have to be better than everyone else around you; you just have to be the first in a new area,” says Baym.
It shows the importance of randomness in evolution “in a really beautiful way, a way that is easy to visualize and thus hard to deny,” adds Yeh. “It’s not just that mutations need to arise, it matters very much where those mutation pops up.”
It is increasingly clear that location matters in infectious diseases. For example, people with cystic fibrosis often develop chronic bacterial infections in their lungs. Those microbes don’t grow as a single uniform population; instead, they form isolated clusters that stick to separate parts of the lung, evolve independently, and often vary in important traits like antibiotic resistance. “There are some really interesting parallels between those infections and the multiple coexisting wavefronts [on the MEGA-plate,” says Michael Brockhurst from the University of York. The latter might be very useful for studying the former.
Beyond any applications in research and medicine, the MEGA-plate also makes for a wonderful teaching tool. It makes the abstract concrete. It vividly brings the process of evolution to life—and to view. “We’re visual creatures,” says Baym. “Seeing is believing.”