‘The frozen mouse droppings were exactly what we needed for our colon cancer research’

Scientists rarely go straight for the target. An ode to the unexpected discoveries. Today: how Hein te Riele’s colon cancer research was revived by frozen mouse droppings.

‘My research is about an early form of colorectal cancer, Lynch’s syndrome. It is a hereditary condition in which parents pass on a genetic defect to their children. This defect affects an important mechanism that counteracts unwanted genetic mutations. As a result, people with this defect are more likely to develop cancer.

‘I’m trying to understand how this process works. For this we use mice, in which we have introduced the genetic defect. These mice get an intestinal tumor very quickly. We then look at how we can reduce the risk of tumor formation.

‘In 2015, I was working with such mice with my PhD student Wietske Pieters, when we had to move to a new, more modern animal facility. That didn’t seem wrong: the new residence was a lot cleaner. The animals were better protected against all kinds of infections.

‘Such a clean facility seemed ideal to us, but once we got to work, our mice no longer developed tumors. We immediately tried to figure out how this was possible. We concluded that it had to be the new, clean environment: all kinds of bacteria were in circulation in the previous building, which apparently played an important role in tumor formation. But now they were absent.

‘We were surprised that the effect could be so strong. To investigate further, we first had to find out what kind of bacteria were present in the old quarters. Unfortunately, that building was torn down. We would never be able to replicate the old conditions again.

‘Until we realized we still had frozen mouse droppings from the previous mouse house. We had used that poop in a completely different study and just never threw it away. If you don’t pay attention, that kind of stuff could still be in the freezer twenty years later, until someone asks if you can take it out.

‘In that poo, Wietske saw which bacteria had been present in the previous stay, exactly what we needed. Some microbes had even survived the freezing cold. Completely by chance, we were therefore still able to investigate the effect of the bacteria on the gut by transplanting the frozen faeces into our mice.

‘And indeed, the mice into whom the old poo had been transplanted developed all kinds of infections, which we also saw in the mice in the old building. In addition, the cells in the intestinal wall began to divide faster, and changes in the DNA occurred more quickly. Still, not a single mouse developed an intestinal tumor.

‘We think that the bacteria do play a role in the disease, but that we do not yet have a complete picture of the conditions in the old building with the frozen faeces. The investigation is still ongoing, because we are definitely on to something important.’