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Monday
Jul122010

Why we get cancer

ResearchBlogging.orgThe short of it...

Creationists often put physicians on a pedestal as the scientists doing the real work in biology, useful work of improving human health and well-being as opposed to the pontificating, abstract work of the evolutionists. But, can we really understand human aliments outside of the light of evolution? Well worn examples of antibiotic resistance vividly illustrate the folly of ignoring evolutionary processes in medicine. Cancer however is another example of evolution in action. Tomislav Domazet-Loso and Diethard Tautz of the Max Planck Institute for Evolutionary Biology in the journal BMC Biology used a technique called phylostratigraphy to trace the origin of the genes associated with cancer to the origins of the cell and the first multicellular animals. The evolution of the first multicellular organisms necessitated a fine balance between the reproduction of individual cells and the evolutionary interests of the multicellular organism. The role of genes involved in cancer is to keep the peace and limit the ability of particular cells to go rogue, curtailing the reproductive success of individual cells in favor of the group. Understanding the evolutionary origin of these ancient genes sheds light on why we get cancer and can light the way to new treatments.

The rest of the story...

Look among the critics of evolutionary biology and among those with any experience in the life sciences you’ll find a fair number of physicians. A well worn argument in creationist circles is that we simply don’t need evolution in fields dealing with basic human health and well-being. Save for some concessions made to account for antibiotic resistance, evolution in the minds of creationists is superfluous arm-waving and of no use to the “real” nuts-and-bolts biology employed by the medical community. The question is this, is it sufficient for your doctor to simply know the mechanics of how your body works and how to patch it back together or is it better for modern medicine to why your body works the way it does and why sometimes it fails? To date only evolution has been able to deal with the ultimate “whys” in biology.

Case in point, take what is arguably the most familiar life-threatening ailment to the general public, cancer. According to the National Cancer Institutes there were over 1.3 million new cancer diagnoses were made in 2007. Cancer is found in virtually all multicellular organisms and can take many forms but in all cases it is essentially the unchecked growth of a particular cell type. Cell division gone wrong can wreck all sorts of havoc on the body and be difficult to treat. The ultimate question regarding cancer however is why do we get cancer in the first place? Sure there are environmental causes, but the environment acts on some aspect of the cell, particular genes for example, causing the normally well-regulated cell cycle to go awry. Why do these genes, when mutated through either action of the environment or by the dumb luck of imperfect replication, cause a cell to go cancerous?

Organisms from dandelions to antlions to lionfish are walking a fine tightrope. Multicellular organisms it seems have struck an evolutionary bargain between the individual and the cell. Much of evolutionary change proceeds through the process of natural selection where some individuals contribute more offspring to the next generation relative to other less successful individuals. Individual organisms therefore are competing with one another for finite resources and their relative contribution to the next generation is dictated in large part to their capacity as a competitor. Individuals are better or worse competitors by virtue of their biological characteristics. Individuals that excel at beating others to the trough pass on those genes underlying their winning characteristics to the next generation. Voila! Evolution by natural selection.

Competition however was not invented by multicellular organisms. Single celled organisms also engage in competition for the resources necessary for survival and reproduction. The trick in the evolution of the multicellular organism was getting all these cut-throat single cells to play nice and contribute to the good of the group. This is a lot to ask of a single cell because in a multicellular organism not all cells contribute to the next generation. Only the gametes go on to make the next generation and the rest of the body’s cells play a supporting role, curbing their evolutionary tendencies to reproduce more than the next cell to preserve the harmony of the group.

This delicate balance between the group and the cell is vividly illustrated in those organisms that are sometimes single celled and sometimes multicellular. While spending most of their lives as single celled organisms, slime moulds and some bacteria called myxobacteria aggregate into multicellular groups when times get tough and resources scarce. The multicellular aggregations of cells of slime moulds and myxobacteria are called fruiting bodies. Fruiting bodies consist of a stalk topped by a fruit-like structure. Cells that form the stalk raise the cells in the fruit above the surface where they turn into tough spores and are dispersed on air currents to more favorable conditions. The cells at the top of the fruiting body live on with a chance to contribute to the next generation whereas the cells that form the stalk sacrifice any chance at their own reproductive success to help other cells.

So, what does this have to do with cancer? Cancer is essentially the upsetting of this ancient evolutionary deal between multicellular organisms and their cells. No longer happy with their supporting role in the multicellular organism, cancer cells proliferate at the expense of the group. Variations arising in genes associated with cancer spread in a population of cells because cancer genes convey a greater reproductive rate and thus a greater evolutionary fitness relative to other cells. It is a little misleading to say there are genes for cancer, rather there are genes playing particular roles in the cell that, if subject to some mutation, can result in the cell proliferation we call cancer. The question is then what are the genes associated with cancer normally doing in the cell and when did they evolve? If the evolutionary explanation is correct then many genes associated with cancer should have appeared with the first multicellular organisms.

Tomislav Domazet-Loso and Diethard Tautz of the Max Planck Institute for Evolutionary Biology asked this very question in a recent paper in the journal BMC Biology using a technique called phylostratigraphy to trace the evolutionary origin of different classes of genes associated with cancer. Remember, there really are no “cancer genes” per se, only genes for various aspects cell growth and metabolism that, when altered, can result in the disease we call cancer. That said, I’ll use the term “cancer genes” for the rest of the blog post, but, you know what I mean. Phylostratigraphy first builds a phylogenetic tree based on whole genome data, maps all the genes of a particular organism to the branch points of the phylogeny and then generates a distribution of genes associated with a specific biological characteristic or associated with a particular disease. This tool provides a means to see if some genes cluster around a particular branching point in evolution history.

So where in life’s storied past did cancer genes first appear? Domazet-Loso and Tautz looked at two classes of cancer genes. So-called caretaker genes are involved in reducing the probability of mutation while those playing a gatekeeper role are involved in cell reproduction, differentiation and cell death. Cancer genes playing a caretaker role tend to cluster around the origin of the cell itself while those cancer genes in the gatekeeper class clustered around the origin of multicellular animals (the metazoans). This makes evolutionary sense given this tug-of-war between the cell and the individual multicellular organism. The first caretaker genes likely appeared with the first cell selected by evolution to stabilize the genome, but, gatekeeper genes likely first appeared at the emergence of the first multicellular life, to regulate cell growth and make certain that individual cells play ball and keep the evolutionary interests of the group above their own reproductive success.  Understanding cancer is therefore intertwined with understanding our some of our earliest multicellular ancestors and the unique evolutionary challenges inherit in living in groups.

Cancer is but another example of the power of evolution to provide insight on human health. Beyond just understanding the “nuts-and-bolts”, evolution gives us a scientific basis to explain the “whys”, “whens” and “what-fors” of human biology. The evolution of the multicellular organism was obviously a critical point in the history of our biology. The genes that evolved during this time were selected to police individual cells for the public good. When these genes are altered the carefully coordinated balance of different levels of evolutionary interest can come undone with devastating consequences. It seems cancer too can not be understood outside of the light of evolution.

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Domazet-Lošo, T., & Tautz, D. (2010). Phylostratigraphic tracking of cancer genes suggests a link to the emergence of multicellularity in metazoa BMC Biology, 8 (1) DOI: 10.1186/1741-7007-8-66

Queller, D. (2003). Single-Gene Greenbeard Effects in the Social Amoeba Dictyostelium discoideum Science, 299 (5603), 105-106 DOI: 10.1126/science.1077742

Velicer, G., Kroos, L., & Lenski, R. (2000). Developmental cheating in the social bacterium Myxococcus xanthus Nature, 404 (6778), 598-601 DOI: 10.1038/35007066

Reader Comments (3)

Really great post! You did a good job explaining in "layman's terms" why we get cancer - something that most people do not understand. Thanks for this

July 12, 2010 | Unregistered CommenterHannah Waters

I truly appreciate your article, your post brings a lot of information that I need. Thanks.

This is a great analogy on the origins and development of cancer. Many people know of cancer but very few know, scientifically, what cancer actually is and how it works.

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