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Impearls: Cancer is an evolutionary process

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Earthdate 2009-08-29

Cancer is an evolutionary process

Figure 1. Cancer is an evolutionary process

F1 Figure 1.  Cancer is an evolutionary process.  “The lineage of mitotic cell divisions from the fertilized egg to a single cell within a cancer showing the timing of the somatic mutations acquired by the cancer cell and the processes that contribute to them.”

Further description of the figure from the Nature article quoted below:  “Mutations may be acquired while the cell lineage is phenotypically normal, reflecting both the intrinsic mutations acquired during normal cell division and the effects of exogenous mutagens.  During the development of the cancer other processes, for example DNA repair defects, may contribute to the mutational burden.  Passenger mutations do not have any effect on the cancer cell, but driver mutations will cause a clonal expansion.  Relapse after chemotherapy can be associated with resistance mutations that often predate the initiation of treatment.”



An illuminating perspective on the nature of cancer has been achieved in that we now realize that cancer is itself the result of a process of biological evolution (random mutation plus natural selection) occurring amongst individual cells within the environment of one's own body.

A technical review article appearing in the renowned scientific journal Nature on the subject of the newly deciphered cancer genome lays out our recent understanding of the nature of cancer: 1

Cancer is an evolutionary process

All cancers are thought to share a common pathogenesis.  Each is the outcome of a process of Darwinian evolution occurring among cell populations within the microenvironments provided by the tissues of a multicellular organism.  Analogous to Darwinian evolution occurring in the origins of species, cancer development is based on two constituent processes, the continuous acquisition of heritable genetic variation in individual cells by more-or-less random mutation and natural selection acting on the resultant phenotypic diversity.

The selection may weed out cells that have acquired deleterious mutations or it may foster cells carrying alterations that confer the capability to proliferate and survive more effectively than their neighbours.  Within an adult human there are probably thousands of minor winners of this ongoing competition, most of which have limited abnormal growth potential and are invisible or manifest as common benign growths such as skin moles.

Occasionally, however, a single cell acquires a sufficiently advantageous set of mutations that allows it to proliferate autonomously, invade tissues and metastasize.

Some people reject this concept, at least on first encounter, believing it to be, as one person put it, ”a misapplication of evolutionary theory,” because “cancerous changes in cells insure their own destruction rather than being passed on to the next [human] generation,” and “thus cancer is better understood as a malfunction [or degeneration] of cellular mechanisms rather than an evolutionary process.”

This argument is wrong, or at best an appreciation of only half of the dual interacting principles that are at work in the onset of cancer.  In this regard, one might note that the authors of the foregoing Nature piece from which the earliest quotation was excerpted are highly experienced cancer researchers and thus hardly naive concerning this topic.  Beyond that mere “argument from authority,” however, though genetic “malfunctions” (aka mutation) do of course occur, the development of cancer goes way beyond a mere haphazard accumulation of defects — which would indeed be inherently far less dangerous — rather, the creation of cancer is propelled by true evolutionary forces.

The typically negative changes that the bulk of accidental genetic modifications to complex biological systems (known as mutations) introduce, subsequently get filtered in living environments by natural selection (random mutations in combination with natural selection being collectively known evolution), leaving only the advantageous (or at least neutral) results behind — advantageous, that is (in the context we're discussing), for individual cell lineages, if not for the body as a whole — which steadily improves the cells of those lineages' reproductive and competitive standing within the body's increasingly diverse cellular environment.

Beyond that, however, taking the above objection at face value would mean that whenever a new species evolves/arises out of another to fit the environment in which it presently finds itself (for instance, humans with their big brains evolving during the last few million years out of stupider hominids) — but which evolutionary alterations happen to ensure that the environment afterwards changes or even is disrupted or destroyed by the actions of the newer species (such as people blowing up the world or making it unfit to live in due to pollution or global warming) so that the species subsequently becomes extinct — that the earlier adaptive changes resulting in the origin of that species would therefore have to be deemed not to have been “evolution”!  Good to know; Creationists must therefore be right: humans didn't evolve!  (End sarcasm.)

Discarding sarcasm, it's important to realize that body cells which are progressing towards a cancerous variety as a result of the dual actions of mutation and natural selection (i.e., evolution) are “fitter” — in that those cells successfully out-reproduce and out-compete for a considerable length of time their more unassuming compatriots within the bodily environment.  It's not till much later (cellular time-wise) that the overall encompassing bodily environment could end up being destroyed as a consequence of the tumor that those cells may eventually grow into.  In the meantime, those cells are responding to real evolutionary forces that propel their progression — not mere haphazard “degeneration.”

It can even occur on occasion that a cancerous line does not get wiped out along with its host!  As it happens there is a variety of cancer in dogs known as canine transmissible venereal tumor (CTVT), also called Sticker's sarcoma (that one can learn about here 2), which, rather than being viral in nature as most infectious cancers are, actually consists of the mutated cells of the original dog that initially developed that variety of cancer, in the course of which somehow evolving the capability to survive and escape from its host, infecting other dogs thereafter in an endless chain, and thus as a result long outliving its original progenitor.

Ignoring the instance of the cancerous dog cell lineage that succeeded in escaping and outliving its bodily host whilst infecting dogs more generally — even more “ordinary” cancers that never manage to escape and live free of their host are remarkable as instances of the body's constituent cells (or rebel lineages of them) learning via evolution how to disobey the body's regulatory apparatus — in effect raising the “jolly roger,” taking up a life of independent piracy within the host, perhaps in the end by their free-wheeling activities killing off their formerly allied-to body.

A page at the University of California, Berkeley, titled “ Another perspective on cancer: Evolution within,“ puts the ultimate evolutionary origin of cancers succinctly: 3

[D]espite increased attention and funding, the cure for this and other cancers has remained notoriously elusive.  Viewing cancer through the lens of evolution helps explain why a cure seems to remain just out of reach and points the way toward new treatments.  Where's the evolution?  Iconic examples of evolution (birds evolving from dinosaurs, hominids evolving an upright posture, or a lineage of lobe-finned fish evolving four legs and moving onto land) might seem unrelated to the growth of a cancerous tumor, but the process underlying them both — natural selection — is identical.  We typically think of natural selection acting among individuals, favoring those carrying advantageous traits and making those traits more common in the next generation.  However, the key elements of this process — variation, inheritance, and selective advantage — characterize not just populations of organisms in a particular environment, but also populations of cells within our own bodies.  The cells lining your intestines, for example, are not genetically uniform; there is variation among them.  Some of those cells have incurred chance mutations as they have divided.  If one of those mutations (or a series of mutations) allows its bearer to evade cell death and reproduce more prolifically than others, it will pass that mutation on to its daughter cells, and cells bearing that mutation will increase in frequency over time.  Like organisms in an ecosystem, cell lineages within one's own body compete for resources.  A cell lineage that gains an advantage in that competition, accumulating mutations that allow it to grab extra resources and escape the body's control mechanisms, will proliferate and may evolve into a cancerous tumor.

One is reminded of renowned science fiction writer (as well as editor) John W. Campbell's chilling tale from 1938, “Who Goes There?” (subsequently made into the 1951 motion picture The Thing from Another World, remade as The Thing in 1982) in which a terrible alien menace, liberated from Antarctic ice, possessed (once unfrozen) the capability of taking over the substance of animal and man, incorporating it into its own flesh and being — whilst (contrary to eating and ingestion as we know it) continuing to present the devoured human or animal's semblance as a “doppelganger” or zombie of that individual.  Thus, an entire kennel of dogs or barracks of humans could, in the context of that story, be surreptitiously consumed one by one and thereby incorporated into the newly revived alien life form.

The thing (pun intended) that saved the folk in that story was that every such subsumed (semblance of a) human or animal, though now fully part of the alien species, was ultimately still an individual that would fight for its own survival when threatened — and simply separating a small part (such as a bit of sampled blood) of the creature whenever its takeover of man or dog was suspected, and then “threatening” that sample (with a hot wire perhaps), would cause the newly separated being to recoil in its own defense (unlike untransformed people's blood), thus revealing the doppelganger.

As a character in story put it, initially blurting out the idea: 4

“Blood is tissue.  They have to bleed; if they don't bleed when cut, then by Heaven, they're phoney from hell!  If they bleed — then that blood, separated from them, is an individual — a newly formed individual in its own right, just as they — split, all of them, from one original — are individuals!”

“Get it, Van?  See the answer, Bar?”

Van Hall laughed very softly.  “The blood — the blood will not obey.  It's a new individual, with all the desire to protect its own life that the original — the main mass from which it was split — has.  The blood will live — and try to crawl away from a hot needle, say!”

It's extremely interesting, I think, that our own body cells turn out to be rather like Campbell's hypothetical alien menace, as they evolve on their own as individuals within one's own body toward an independent, if piratical, existence.

Realizing that cancer results from an evolutionary progression amongst the cells within one's own body provides an illuminating perspective with regard to the fundamental nature of cancer, revealing just why it is that cancer so often proves resistant to treatment (as cancerous cells simply evolve away from a given regimen unless every last tumor-generating cell is thereby destroyed), as well as suggesting a number of avenues along which the phenomenon may be mitigated, obviated, and (one hopes) ultimately defeated.


References

F1 Figure 1 from the Ref. 1 Nature article.

1 Michael R. Stratton, Peter J. Campbell, P. Andrew Futreal, “The Cancer Genome,” Nature, Vol. 458, Issue no. 7239 (9 April 2009 [2009-04-09]), pp. 719-724.

2 Carl Zimmer, “A Dead Dog Lives On (Inside New Dogs),“ The Loom, August 9, 2006 [2006-08-09].

3Another perspective on cancer: Evolution within,” October 2007 [2007-10], part of: “Understanding Evolution,” University of California, Berkeley.

4 John W. Campbell (under the pseudonym Don A. Stuart), “Who Goes There?”, August 1938 [1938-08], Astounding Science Fiction, Street & Smith Publications, Inc., New York.  Collected in: The Best of John W. Campbell, Edited with an introduction by Lester Del Rey, Nelson Doubleday, Inc., Garden City, New York, 1976, pp. 246-298; quote on p. 291.  Also collected in: John W. Campbell, Who Goes There?, Shasta Publishers, 1948.  Made into the motion picture The Thing from Another World, directed by Howard Hawks, Winchester Pictures, distributed by RKO Radio Pictures, 1951.  Remade as The Thing, directed by John Carpenter, distributed by MCA / Universal Pictures, 1982.



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