Gaia, cancer, and the “holobiont”.

I just got back from a trip to Dalhousie University, to which I was invited by grad students to speak in the Department of Biology. Among the many interesting conversations was one I had in which Gaia and cancer somehow came together. My host, Sarah Salisbury, and I were speaking with Dr. Ford Doolittle and Andrew Inkpen, about their ideas on how natural selection might act at the level of processes – as opposed to the “things” that generate those processes. I won’t spill the details as they will be outlined in a forthcoming paper of theirs. However, I did want to relate how we got from Gaia to cancer and, then, during the course of writing this post how I ended up at the holobiont. (Get ready for a lot of “scare quotes” as I try to extend terminology in each of these areas to the others.)

Dalhousie is 200 years old - how cool is that. 

According to Wikipedia, the Gaia hypothesis “proposes that living organisms interact with their inorganic surroundings on Earth to form a synergistic and self-regulating, complex system that helps to maintain and perpetuate the conditions for life on the planet.” One way of framing this hypothesis is that global ecology and the evolution of life feedback to one another in such as way as to facilitate and maintain life on earth. Taken to extremes, one could say that natural selection favors the self-regulating feedback itself as life would otherwise cease to exist – but how would we ever test this hypothesis?

Here is the top hit in a Google search for "Gaia". SOURCE

In group selection or “higher-level selection” arguments of this sort, one would normally need multiple entities with heritable traits influencing differential “survival” and “reproductive success”. In the case of Gaia, then, we would need life originating on multiple planets among which selection was then occurring – because it is impossible to have selection among things if you only have one thing. Of course, one might argue that selection has indeed acted in this way and that our planet (or others we can’t perceive) is the only one left – because life did not evolve synergistic self-regulation on other planets and therefore went extinct. Or one might argue that selection on our Earth has weeded out organisms that do not participate well in this synergistic self-regulating system. Any of these speculations could well be true, but it is impossible to study such processes in the real world because we only have the one world.

Or do we really only have one world? As we were discussing Gaia, I started to think that perhaps we could use cancer as a Gaia model. Consider the similarities. Cancer starts with a single cell than then proliferates into a great diversity of descendent cells; much as current life on Earth has proliferated and diversified from a single initial cell. Then, the cancer that proliferates on an individual “host” organism will (in most cancers) leave no descendants when that organism dies; just as we might expect that (barring colonization of new planets) life on earth will cease to exist when the Sun has run its course. In addition, cancer can kill its host and be the reason for its own extinction, as well as most other life occupying that host; just as some life – us perhaps –could severely damage the Earth and kill much of the life on it. Thus, perhaps we can view cancer as a lineage of organisms proliferating on its own finite planet that, should the cancer disrupt the synergistic self-regulation of that planet, the cancer itself and much of the life on that planet will cease to exist. Considered in this way, perhaps we can – at least for the sake of argument – speculate on how cancer and its proliferation in individual hosts might yield insights into the Gaia hypothesis.

An awesome book on cancer.

When I started this post, I was thinking that much of the analogy from cancer would seem to parallel ideas supporting the Gaia hypothesis: for instance, “nicer” (as opposed to “meaner”) cancers should leave the host alive longer, nicer cancers should enable the persistence of more life on the host for longer, and so on. Indeed, all of these things are true. However, it now seems to me that one fact runs directly counter to the Gaia hypothesis: cancer exists, is common, and routinely kills its host. This fact might be taken to mean that selection does not generally favor a synergistic self-regulating system in the context of cancer and its “planet”. Why might this be? I speculate it is because cancer (the non-heritable kinds) are never transmitted to other hosts – that is, to other “planets.” In this case, selection would never favor cancer being nice to its host because, no matter how long the host lived, the cancer would never be passed on: as opposed to infectious/transmittable diseases of hosts where selection can indeed favor reduced virulence. For this reason of non-transmissibility among hosts/planets, presumably selection cannot act among the cancer/life on different hosts/planets to favor synergistic self-regulating systems on those hosts/planets.

Ok, wait, you might say, cancer is actually nice to its host because it rarely strikes before reproduction: however, the reason here isn’t selection on the cancer but rather selection on the against alleles in the host genome that increase the chances of pre-reproductive cancers. That is, it isn’t selection on the inhabitants of the hosts that favors synergistic self-regulation, rather it is selection on the host itself. Unlike hosts, however, planets do not have genomes that can be selected to “punish” lineages (species) that are not nice to the overall system. Or is that true? What if we consider all life on the planet as its genome – in this case, the “genome” of a planet perhaps could be selected to eliminate parts of that genome that do not promote self-regulation. That is, life could self-police itself through elimination of non-cooperative life. Interestingly, even this analogy could perhaps be extended to the cancer scenario: all the genes in a host, including all genes in all species living on or in that host (the so-called “hologenome” or “holobiont”), could be selected to act against cancers that are detrimental to the host itself.

The top hit on Google for "hologenome". SOURCE. 

I am not sure if any of this is useful in anyway, but it sure is interesting – to me at least. I have no intention of actually studying or testing these ideas in any way, but I have certainly been interested in the evolution of cancer for some time. For instance, here is a previous post in which I speculated about the fundamentally different problem posed by cancer relative to other forms of life that are detrimental to humans. In addition, I have recently become very interested in the microbiome (a key part of the holobiont) as regulator of fitness and adaptation. Indeed, just today, my student Lotte Skovmand, had her qualifying exam, which she passed (Congratulations Lotte!), in which she will examine the drivers of microbiomes in plants and howler monkeys. Perhaps that is how I got from Gaia and cancer last week all the way – today – to holobionts. Nothing like colleagues and students to get you thinking about new things!