Researchers have gained much insight by examining cancer through the lens of evolution, a perspective pioneered by Peter Nowell and John Cairns in the 1970s. All the same forces are at play. Mutations arise, sometimes conferring advantages or disadvantages, and are subject to selection and drift. The key difference is one of perspective: while the evolution of eukaryotic populations involves multicellular individuals, cancer cells represent their own populations like pathogens infecting a host. In such a situation, what benefits the cancer — namely, uncontrolled growth — may very well lead to the destruction of the host, the cancer’s own environment. Just as C. S. Lewis reminds us of love, “The highest does not stand without the lowest.”

One is consequently tempted to ask whether anything can be learned by turning the lens around: has cancer anything to teach us about the origin and evolution of our species as a whole? Over at Peaceful Science, Dr. S. Joshua Swamidass offers an “important article” on this theme, “written after [his] first Nature Genetics paper.” His piece argues that “Cancer is only possible because life evolves” and that “[s]everal new functions are required,” and he later comments that by “the same definitions used by ID [intelligent design], [cancer] can innovate.” At BioLogos, the same author goes further, claiming that “if many ID arguments in molecular biology were true, then cancer as we know it would be mathematically impossible.” 

A Welcome Challenge

Readers of Evolution News may be familiar with Swamidass, of Washington University in St. Louis, whose review of the volume Theistic Evolution has been the subject of recent weighing by Ann Gauger. Jonathan Wells has also addressed the cancer argument. Swamidass is an ID critic who attempts to answer design arguments on their merits. This sets him apart from many others who are content with mere name-calling. His challenge is welcome and merits further discussion.

How can it be that cancer so readily acquires advantageous mutations subject to selection, when it is prohibitively difficult to find examples of mutations with such effects at the organismal level? The answer has been clear since at least 1976, when Nowell wrote that “neoplastic traits appear usually to reflect alterations in the expression of preexisting genes rather than structural gene mutations.” More recently, Crespi and Summers have documented the six hallmarks of cancer as follows:

1. self-sufficiency of cells in signals controlling growth;
2. loss of sensitivity to antigrowth signals;
3. evasion of apoptosis via mutation or loss of gatekeeper genes; 
4. development of limitless replicative potential, usually via the expression of telomerase;
5. sustained angiogenesis, whereby the blood supply to a tumor is augmented; and 
6. tissue invasion and metastasis, which causes 90% of cancer deaths.

Each of the above is achievable via myriad functionally equivalent mutations in similar sets of genes, and none produces sequences encoding novel protein folds. This is possible because cancer involves breaking regulatory mechanisms, and there are numerous ways to do so. It is easier to destroy a bridge than to build one — and if the destruction happens to be beneficial, by all means it will be favored (think of Behe’s “first rule of adaptive evolution”). Although in the parlance of cancer research such mutations are termed “gain of function,” the gain is merely one of activity; the genetic basis is loss, namely, loss of functional regulation that was once able to hold growth in check.

A mutation need not be constructive to be adaptive. Cancer is perhaps the very best example.

Far from representing special pleading by closet creationists, the above distinction is ubiquitous in the educational and technical literature alike. Comparing the evolution of eukaryotic species and cancer cells, Woo and Li state quite simply that “the two differ in many ways, such as timescale… and outcome of the evolution.” Essential Cell Biology explains that “gain-of-function” mutations in cancer represent “overactivity mutation[s]” that “make the affected gene product hyperactive” (730), and the Dictionary of Biology points out that “Gain-of-function mutations are often expressed in tissues where the gene is not usually transcribed” (470). Lauren Merlo and colleagues go even further:

“The relatively short time frame, and the large-scale genomic alterations in neoplastic progression suggests that neoplastic cells will be unable to evolve complex adaptations to their environment. Most neoplastic mutations seem to remove pathways that suppress proliferation or trigger apoptosis, or co-opt pathways normally used in development and wound healing.” [Emphasis added.]

A Semantic Argument

There can thus be no doubt that it is a mistake to treat carcinogenic “gain of function” mutations as the same phenomenon needed to construct new complex adaptations. The argument is semantic only. What is observed in cancer is either irrelevant or diametrically opposed to what is required for the evolution of novel biological function.

Swamidass writes:

Cancer demonstrates there are thousands of possible mutations that could evolve the same functions. There are a very large number of ways to solve the problem. This makes evolution more likely, because no single specific set of mutations is required to generate a new function. Instead, evolution has only to find one of the many solutions. This makes it much easier for new functions to arise.

Yes — if by “new function” a loss is meant. But one cannot get rich by going broke, even when poverty is temporarily advantageous. As Michael Lynch points out in a characteristic understatement, “Given that life originated from inorganic matter, it is clear that there has been an increase in phenotypic complexity over the past 3.5 billion years.” Certainly this involved more than “alterations in the expression of preexisting genes” or else their destruction?

Cancer proves evolution only insofar as one forgets, or pretends not to know, what evolution is supposed to explain.

Overwhelming Loss of Genetic Information

The fact that cancer involves overwhelming loss of genetic information was recently made unambiguous by Inigo Martincorena and colleagues, who demonstrated a near-complete absence of negative selection in cancer cells. This is the type of selection involved in preserving functional elements by eliminating deleterious mutations, and is widespread in multicellular organisms, consistent with the neutral theory. It turns out that less than 1 percent of coding mutations in cancer lines are eliminated by such selection in humans, fewer than one per tumor, implying that over 99 percent are free to accumulate as if neutral. Only 20 to 30 genes in the whole genome may be under negative selection in cancer, but none significantly so. 

The most straightforward explanation is that relatively little genetic information needs to be maintained for cancer to succeed. Cancer and species evolution could hardly differ more.

In stark contrast to the paucity of negative selection, Martincorena et al. find a whopping 400-500 genes under positive (favorable) selection as cancer drivers, with a typical tumor containing four driver mutations. Nonsense (protein-truncating) mutations are usually favored even more than simple amino acid changes. When it comes to the tumor suppressor gene TP53, over 95 percent of mutations changing or truncating the protein may be positively selected. In other words, there is almost no mutation that won’t do the trick. Presumably mutations creating biological novelties are not so common.

Swamidass goes on to write that “Cancer evolution independently confirms that [the] neutral theory is correct.” Why the abundance of neutral fixation events in cancer lines should have any relevance whatsoever to the applicability of the neutral theory, apparently to eukaryotic species, is elusive. Of course the neutral theory is correct.

The “Edge of Evolution”

We are left only to ask whether Swamidass’s description of cancer — namely, that there are “a very large number of ways to solve the problem” — also applies to the emergence of biological novelty. Fortunately, this question has been a focus of ID research for over a decade. Given that the “definitions used by ID” and “many ID arguments” referred to by Swamidass have not been specifically cited, we suggest the work of Michael Behe, Douglas Axe, and Ann Gauger, for starters. None question the ability of selection to promote an advantageous trait in a population. All suggest that a prohibitive “edge of evolution” is encountered when approximately three to six coordinated mutations (depending on assumptions) are required at specific residues to achieve a beneficial innovation.

Especially apropos is a paper in which Gauger and Axe compare highly similar homologous genes encoding distinct molecular functions and attempt to engineer an evolutionary pathway between them. They find that no fewer than seven coordinated changes are required. Theoretical considerations suggest that this number is utterly out of reach in the history of life. It follows that, if they can’t arise, they can’t be selected.

So, cancer proves selection. Did anybody doubt it? That cancer proves a creative capacity for evolution — specifically, an evolutionary account for the origin of some or all biological novelty — is a far more dubious proposition. Destructive carcinogenic mutations are, apparently, convincing enough for Swamidass. In the absence of details, it is difficult to assess why this is so.

Photo: S. Joshua Swamidass, by permission of Dr. Swamidass.