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Dispatches from the Future | Episode 6

When Cells Die: A Conversation with Doug Cole and Volker Herrmann


Doug Cole

Managing Partner


Volker Herrmann

CEO-Partner and CEO of Sonata Therapeutics

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Two life sciences pioneers discuss why cell turnover is so important to health and disease.

Jason Pontin: Why is cell turnover so important? Why do we care about cell turnover at all?

Doug Cole: Cell turnover is one of the most ubiquitous and fundamental features of biological systems. In every biological system cells are turning over constantly. And how they turn over has a lot to do with whether the individual is healthy or is not healthy. And so it's really critical if we are to understand fully what sustains the health of the individual and the circumstances in which disease emerges. It's essential that we understand cell turnover.

JP: If we define cell turnover more broadly to be what Inzen is calling Thanokine Biology, what functions do these signals perform in the human body?

DC: Maybe a good way to understand this is to put oneself, if you can, in the position of a cell in the body. You realize that that cell is living in a particular neighborhood—a micro-environment is the word that people are using scientifically now—and it's intuitive to expect that the cells success at sensing those inputs and reacting to them in appropriate ways might be essential to its ability to thrive as its micro-environment changes. And with that in mind, one can ask, well, what are what are the factors that contribute to that microenvironment?

One of them is very obvious: other living cells. Every every cell is surrounded by other living cells. And we know that living cells signal to other living cells all the time. We think of that kind of information as what the endocrine system does; where the signals arise from distant regions; what paracrine signals are; which are cells that arise from cells that are right next to signals that arise from cells that are right next to each other. We think of cytokines, which are a very important type of signals. They come from the immune system and so on. So living cells are well recognized as an important cell source of inputs to other living cells.

Another important source, of course, is the environment itself. What the individual consumes through through diet, what the individual is exposed to through the air and other environmental sources, which can benefit a particular cell or can harm a particular cell. And so, again, how a cell processes these inputs is critical to the phenotype and the status of that cell.

“Turnover is… happening all the time. And the question is, how does that turnover influence the cells that are exposed to it?”
Doug Cole

It turns out, however, that much less attention, if any, has been paid to a third critical source of input, and that is cells that are turning over. Turnover is such a fundamental feature of biological systems, it's happening all the time. And the question is, how does that turnover influence the cells that are exposed to it? If you were a cell and a cell near you was turning over into stress because of a threat, at the very least you would want to know that, and then you would want to adapt as best you could to withstand the same fate. If that cell near you was turning over as this part of the due course of life and the cycle of life that might tell you everything is okay and you could keep operating the way that you have been. So it is the importance of this overlooked source of input to cells, which is a critical function that that we need to understand and that we believe we can harness.

JP: What do I get from this approach that I wouldn't get from other therapeutic approaches?

Volker Herrmann: Let me start by saying that's the first thing we're excited about; pretty much everywhere we've looked, we've seen that thanocrine signaling is important and plays a role. But we will first focus on cancer and fibrotic disease. So let's start with cancer. Today most companies either are focused on finding new targets to selectively kill cancer cells. And that's great.

At Inzen we're taking a bit of a more comprehensive approach. We certainly like to kill cells, but we also like to think that we can do it in a way that's very different from anybody else, that actually also allows us to influence the tumor environment and drive a much more sustained immune reaction to kill off the remaining cancer cells. I'm not aware of anybody else currently taking that approach.

Secondly, we have insights that I think make a great combination of opportunities. We see that about 30 percent of cancer agents being used today in the clinic actually do kill cancer cells, but they do it in a way that actually suppresses t-cells. Now, imagine a world in which you increase your efficacy and efficiency of all of those drugs substantially and makes for a great opportunity for combination therapy as well. Thirdly, we are, of course, looking for a fundamentally new targets.

Editor's note: This conversation has been edited for length and clarity.


Dispatches from the Future