Scientists and doctors have been trying to use bacteria to fight cancer for more than a century. In 1891, the surgeon William Coley infected cancer patients with Streptoccocus, thinking that the microbes would trigger an immune response that would also destroy the cancer cells. Coley treated over a thousand people in this way, and although some recovered, others didn’t. Amid mixed results, the approach fell into neglect.

It resurfaced when doctors started realizing that tumors were not sterile, as had long been thought, but often contains multitudes of microbes. The oxygen-hating bacteria that thrive in our gut can readily grow in the interior of tumors, which are similarly low in oxygen and sheltered from patrolling immune cells. The presence of such microbes was attractive to scientists because one of the big challenges in cancer medicine is actually getting drugs into tumours in the first place. If tumour-seeking microbes could be engineered to make those drugs, they could be the perfect Trojan horses.

First, you need to pick the right microbe. Salmonella is a good choice. It can survive without oxygen and readily accumulates in tumors. It’s also closely related to Escherichia coli, the favoued bacterium of the modern biologist. Which means that all the techniques that geneticists have developed for engineering E. coli can be used to modify Salmonella too. “We can quickly leverage an enormous toolbox,” says Hasty.

But, wait—bacteria are living things. They grow. They multiply. They trigger immune responses. Other scientists have tested engineered strains of drug-delivering Salmonella, with poor results. “We killed our mice,” says Seigfried Weiss from the Helmholtz Centre for Infection Research. “They had such a high load of bacteria that they probably suffered a toxic shock.” So if you want to use Salmonella to shuttle drugs into tumors, you need some way of controlling their numbers.

That’s what Hasty’s team, led by student Omar Din, developed. They started with a de-fanged strain of Salmonella that doesn’t cause disease, and gave it the ability to make an anti-tumor drug. They also added genes that bacteria-killing viruses use to destroy their victims, and cleverly wired these up to genes that Salmonella and other bacteria use to sense each other.

The result is a medicine-making microbe with built-in population control. Once the population hits a certain size, 90 percent of the cells rupture synchronously, releasing their cargo. The survivors can then repopulate, and the whole cycle beings again, like clockwork.

Of course, “you’re still putting in a live Salmonella strain,” says Beth McCormick from the University of Massachusetts Medical School. They might be neutered but they’re still bacteria, and they could still trigger inflammation and other immune problems. “But these synchronized circuits allow a persistent but low state of infection, which might overcome the issue with immune responses. It’s a great preliminary step.”