Scientists rarely go straight to the goal. An ode to unexpected discoveries. Today: How Hein te Riele’s colon cancer research was revived by frozen rat droppings.
My research is about the early form of colorectal cancer, Lynch syndrome. It is a genetic condition in which parents pass 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 am trying to understand how this process works. For this we use mice, where we have introduced the genetic defect. These mice develop an intestinal tumor very quickly. Then we look at how to reduce the risk of tumor formation.
In 2015, I was working with rats like this with my PhD student Whitske Peters, when we had to move to a new, more modern animal facility. This doesn’t sound wrong: the new housing was much cleaner. The animals were better protected from all kinds of infections.
Such a clean facility seemed perfect to us, but once we got down to business, the mice no longer developed tumors. We immediately tried to find out how that was possible. We concluded that the environment must be fresh and clean: all types of bacteria were circulating in the previous building, which apparently played an important role in tumor formation. But now they are absent.
We were surprised that the effect can be so strong. For further research, we first had to find out what type of bacteria were in the ancient quarters. Unfortunately, this building was demolished. We will not be able to repeat the old conditions again.
Until we realized we still had frozen rat droppings from the rat’s previous home. We’ve used this tube in a completely different study and we’ve never gotten rid of it. If you don’t pay attention, this kind of thing can still be in the fridge after twenty years, until someone asks if you can take it out.
In that stool, Whitsk saw the bacteria from the previous residence, exactly what we needed. Some microbes even survived the bitter cold. Quite by chance, we were still able to investigate the effect of the bacteria on the gut by transplanting frozen feces into our mice.
Indeed, the mice in which the old feces were transplanted developed all kinds of infections, which we also saw in mice in the old building. In addition, the cells in the intestinal wall began to divide faster, and the changes to their DNA occurred more quickly. However, none of the mice developed an intestinal tumor.
We think bacteria play a role in the disease, but we don’t yet have a complete picture of conditions in the old building with frozen stool. The investigation is still ongoing, because we are definitely going to achieve something important.
Hein te Riele He researches the genetic causes of cancer at the Netherlands Cancer Institute in Anthony van Leeuwenhoek. To this end, he and his group are working to develop new methods of genetic modification to induce tumor formation in a controlled manner.
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