Athena Aktipis - Cancer across kingdom

Kat - Another researcher who's trying to solve Peto's Paradox by taking an evolutionary view is Athena Aktipis from Arizona State University, who's been looking in more depth at cancer rates across the animal kingdom.

Athena - I see cancer really as a fundamental problem for the evolution of multicellularity because in order to build a multicellular body, the cells have to cooperate to inhibit the cell proliferation, control cell death. But also, distribute resources and divide labour, and do all sorts of other things that you need to do in order to make a large body that can be effective. And really, cancer is this fundamental breakdown of cooperation in a multicellular body.

Kat - It's kind of cells going rogue and saying, "I'm not going to be brain cell or a skin cell. I'm just going to do my own thing."

Athena - Yeah. You could sort of think of it in that way. Having a multicellular body work well means that the cells within it are following certain rules, and those rules are encoded genetically with tumour suppressor genes that are making sure cells aren't dividing out of control, making sure that cells are expressing the right genes for the tissues that they're in, and making sure that they're producing the right proteins. So, all of those things break down in cancer and what you get are really misbehaving cells and the result of that is that you can get a malignant growth that can take over and eventually kill a patient if it's not treated properly.

Kat - Are cancer cells really kind of cheaters? They'd be getting around the rules of the society the body and doing what they want.

Athena - Yeah. So, you can think about cancer cells as cheaters in the sense that in general, we can think of cheating as breaking some shared rules. You break some shared rules that you have with a group. In cancer, the shared rules are being broken and those shared rules are actually encoded in our DNA. There are DNA repair mechanisms that are literally getting broken and allowing those cells to get around the shared rules that enabled multicellularity in the first place.

Kat - You're studying the links between cancer and evolution. What do we know sort of where cancers comes from and where is it going, and how do we fit in as humans to the rest of life?

Athena - There are two different answers to that question. So one, is the question of, where does cancer come from for any given individual? The answer is that cancer is a result of a sort of evolutionary process within the body where the cells that are proliferating more quickly, the cells that are monopolising the resources better, that cells that aren't dying when they have too much DNA damage. They're increasing in frequency in the population and that means that what happens over the course of a lifetime is that within the body, selection actually favour cells that are neoplastic, cells that are not behaving properly unless immune system is able to get them under control. So, within an individual, cancer comes from that evolutionary process. But then if we look at the evolution of life in general, what we see is that just the formation of multicellularity. In order to do that, you have to suppress cancer or at least the primordial version of cancer which is cells not inhibiting their proliferation properly, cells not sharing resources with neighbouring cells, cells not cleaning up after themselves. All of those things are sort of the primordial elements of multicellularity. And really, suppressing cancer is a problem that goes back to the evolution of multicellularity and even earlier, even before multicellularity was necessarily about discrete organisms. But when cells started living nearby each other enough that they had to start behaving a little better than they might if they were just on their own.

Kat - There were lots and lots of different species in the world of all sorts of different sizes and there's this famous paradox that you expect bigger organisms because they've got more cells, maybe they should get more cancer and particularly if they live longer, small organisms should maybe get less. But that's not what we see. Tell me about the kind of patterns that we see in cancers across different species and where humans fit in.

Athena - Yeah. Well, you know, if we look across species, we do see the sort of general trend in this paper that we just recently published, Cancer Across the Tree of Life, where the more complex forms of multicellularity and the species that are larger compared to much simpler species do seem to have more cancer reported. But if you actually look at say, within mammals or animals more generally, if you would just look at body size and cancer, you might expect larger organisms to get more cancer because they have more cells, but that isn't the case. So, elephants for example have really low rates of cancer. One of the ideas of why that might be the case is that if you have an organism that reproduces really late and has to grow really large, it's probably worth it for that organism to invest more in suppressing cancer than field mouse that runs about for a year and then gets picked off by a predator. For an animal that is only going to live that long and is going to start reproducing when it's a few months old, it doesn't necessarily make sense to invest in all those cancer suppression mechanisms especially if they come at some cost to reproduction or to wound healing or whatever the trade-offs might be.

Kat - In terms of where humans fit in to that picture - we don't really live fast and die young like a field mouse, we're not as big as an elephant - does our cancer risk kind of fit somewhere in the middle?

Athena - Modern humans do have higher cancer risk than we might expect. I think there's open questions about the extent to which those are driven by environmental exposures that sort of have to do with mismatch between the environment that we evolved in and our current environment. But there are some cancers for which it does seem like a pretty convincing case. There might be some contribution that really is coming from the fact that we live in a world that's really different from the world that we evolved in.

Kat - We're starting to understand a lot more about cancer, about how to treat it, how it starts, looking at the genetics of cancer. It seems quite a recent advance to be bringing evolution into this mix. Why do you think it's important that we do bring an evolutionary view to our studies of cancer?

Athena - Interestingly, evolution has been accepted as a theory of cancer for decades. I think recently it has made a resurgence because it's become much easier to look at the evolutionary process because of how inexpensive it's become to look at genomics and to have huge datasets at our fingertips to examine some of these evolutionary questions.

Kat - Arizona State University's Athena Aktipis.