Carl Zimmer has an article in the upcoming edition of Scientific American that looks at cancer from the perspective of evolutionary biology. The most obvious parallel is that of cancer cells within an individual modeled as an evolving population:
Rare mutations, for instance, may cause a cell to lose restraint and begin to multiply uncontrollably. Other mutations can add to the problem: They may allow deranged cells to invade surrounding tissues and spread through the body. Or they may allow tumor cells to evade the immune system or attract blood vessels that can supply fresh oxygen.
Cancer, in other words, re-creates within our own bodies the evolutionary process that enables animals to adapt to their environment. At the level of organisms, natural selection operates when genetic mutations cause some organisms to have more reproductive success than others; the mutations get "selected" in the sense that they persist and become more common in future generations. In cancer, cells play the role of organisms. Cancer-causing changes to DNA cause some cells to reproduce more effectively than ordinary ones. And even within a single tumor, more adapted cells may outcompete less successful ones.
But multicellular organisms have also evolved mechanisms to suppress such runaway populations of cells. A group of researchers, however, noticed that there is a tradeoff between regulating cell division and aging. Their study of the tumor suppressor gene p16 in mice revealed that:
Natural selection favors anticancer proteins such as p16, but only in moderation. If these proteins become too aggressive, they can create their own threats to health by making bodies age too quickly.
The effects of natural selection on tumor suppression genes is greatest prior to and during prime reproductive age -- once you can no longer reproduce, your ability to transmit your alleles is greatly limited (grandmother hypotheses aside). Therefore, our body is optimized to fight early onset cancers, but is not so great at dealing with those that strike at old age.
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Cancer makes sense when seen as evolutionary mechanisms doing what they always do. Why this should surprise anyone is what puzzles me. Evolution operates over all scales of time and all scales of size. Anything which exempted certain scales would put itself at a disadvantage, and would be favored for extinction.
The McArthur Fellow, my former neighbor and friend, the late Octavia Butler, published the "Xenogenesis" trilogy of science fiction novels. In them, the interstellar traders come to Earth. The most valuable thing we have to trade is: cancer. They have a chemical sense for genetic structure, and find cancer a fascinating evolutionary development, unique in the known galaxy.
Question: If oncogenes are of very great age (Shilo and Weinberg estimate that they originated 800 million years ago) and if evolutionary theory predicts the elimination of genes capable of killing juveniles how does one account for the fact that oncogenes manage to kill modern juveniles?
Answer: The theory of evolution needs a radical revision.
Oncogenes are mutated forms of genes necessary for cellular functions. For example, many genes regulate the cell cycle -- mutations in those regulatory genes lead to runaway lineages of cells that ignore the biochemical signals that usually prevent further cullular division.
I know that genes that cause cancer also perform beneficial functions.
Let me rephrase: Why hasn't natural selection eliminated the ability of oncogenes to kill juveniles?
My suggested revision of evolutionary theory fixes the problem. It proposes evolutionary change itself led to increases in lethal juvenile cancer. As noted by Crespi and Summers in "Positive Selection in the Evolution of Cancer" (cited in Carl Zimmer's SciAm article):
"As first described by Graham (1992) in his book Cancer
Selection, strong selection ... can also lead to increased cancer risk as a pleiotropic byproduct, although here the effects are expected to be less pronounced. For example, artificial selection for large size has led to greatly-increased cancer rates in some breeds of dogs (Graham, 1992; Leroi et al., 2003), and pediatric cancers of humans appear to be concentrated in two tissues, brain and bone, that have undergone rapid phenotypic changes in their developmental trajectories along the human lineage (Graham, 1992; Leroi,Koufopanou & Burt, 2003). In these cases, rapid evolution drives the genotype away from the optimum, increasing the risk of cancer as a result (Galis & Metz, 2003; Leroi et al., 2003). Such cases may typically be transitory, disappearing once the species or population has adapted to the changes, or they may lead to positive-feedback cycles of oncogene evolution, leading to improved tumour suppression, greater developmental precision and complexity, and further adaptive changes driving pleiotropic oncogene evolution (Graham, 1992)."
That lethal juvenile cancer led to "greater developmental precision and complexity" is another essential part of my theory.
Although my book is cited in two of the papers Zimmer cites in his article he doesn't mention it ... or me.