Friday, July 29, 2011

Random Thought: A Response to Carcinogenesis as Speciation.

In a recent article that has been making its rounds in layman news media, Duesberg et al. (2011) have been proposing that carcinogenesis should be considered speciation. In other words, this means that cancers should be considered new species and that the formation of cancers are, in fact, the creation of new species. This paper is both intriguing and shameful at the same time.

The premise is that cancers both karyotypcially (chromosome composition and number) phenotypically (characteristics) unique. Individual cancer cells have variance with respect to each other (there are individuals (they aren't just all clones of each other). Finally, cancer can reproduce. Satisfying these conditions qualifies cancers as species according to the authors.

The authors' theory of cancer speciation is as follows:
  1. Carcinogens cause aneuploidy in normal cells
  2. Aneuploidy (increases or decreases in chromosome number, usually fatal), which is inherently unstable, would create increasing numbers of random karyotypes.
  3. Most of these new karyotypes will be lethal and will not reproduce
  4. A select few of the new karyotypes will be relatively stable and also be able to reproduce and survive
  5. Variance will be introduced as subsequent generations of new karyotypes born from the survivors will only survive if they are also stable enough to survive
The remainder of the article details how this theory explains some of the inconsistencies of the mutation theory of carcinogenesis (the accumulation of mutation in certain genes will initiate cancer/tumour growth).

Overall the article is well written and many of the points seemed valid. The thing that I dislike about this paper is that I find that it was the academic equivalent of a shock piece or sensationalism. The article wasn't really about speciation at all. The article merely used the term speciation and the concept that cancer are unique parasitic organisms to gather attention to the argument that cancers are cause by aneuploidy rather than by gene mutations.

A quick search reveals that a sizable portion of the literature pertaining to aneuploidy's causative relationship to carcinogenesis was authored by the primary author of this paper. I'm too unread in the literature to take either side of the mutation vs aneuploidy debate. However I will make a comment on the speciation claim.

Speciation, is in essence, evolution in action. Leaving aside the philisophical/practical debate of what exactly defines a species, evolution/speciation should occur as follows:

  1. Population exists with variation between individuals
  2. Some external stimulus or selective pressure acts upon the population
  3. Individuals whose variance gives them an advantage survive and breed
  4. Gradual shift will eventually accumulate until the population is no longer the same species as the population it was descended from.
With this as the criteria/description of speciation, we see a problem with the authors' use of the word. Should we consider carcinogenesis as speciation, we may have to alter our perception and definition of evolution. In this paper, the external stimulus acts upon a population (we're good so far), and then induces variation (not so good). The variation is self propagated. Now here I'm a bit conflicted. In one way, I almost argue that this propagation is almost Lamarkian, the other way to look at is just an accelerated mutation (Darwinian). Here's were things really get wonky. The variance produced by the unstable karyotypes is weeded out by mere survivability. Instead of the fittest being chosen and propagating in the face of a selective pressure, the least unfit cells are chosen and propagate without selective pressures. This is akin to having the slowest surviving antelope getting the most mates.

In my opinion carcinogenesis is not speciation. If it were to be considered speciation, we would have to take a real good look at our current theories of evolution and do a re-evaluation. This paper was a shameful use of sensationalism in an academic setting in order to further the 'credibility' of one group's theories. It presented old information under a shocking facade in order to attract publicity.

Duesberg, P.; Mandrioli, D.; McCormack, A; and Nicholson, J.M.. (2011). Is carcinogenesis a form of speciation? Cell Cycle. 10(13):2100-2114