I’ve been so disappointed in the journal BioEssays lately. It hasn’t gotten bad, exactly, it’s just changed, moving away from my interests. It used to have lots of papers on developmental biology, and now it rarely does; I think it’s since Adam Wilkins left the journal staff.
But every once in a while I still check in. I may have to change my mind about the quality. They’ve published an article on cancer by Lineweaver, Davies, and Vincent, on their absurd “atavistic theory of cancer”. It’s embarrassingly bad — I’ve written about it before, and Davies openly admits that it’s based on … Haeckelian recapitulation.
You should be dumbfounded by this revelation.
That’s right, these guys have a knowledge of developmental biology and evolution that is built around a discarded theory from the 19th century. They want to argue that cancer is a reversion to a genetic program that is still lingering intact inside cells, which codes for a solitary existence as a selfish, single-celled microorganism. They are proposing that ancient genes are operating inside cancer cells, but that the more recent genes, the ones important in multicellular cooperation, are damaged or lost. It’s complete nonsense.
It is so bad, so contrary to any modern understanding of molecular biology or evolution, that I have no idea how it got past any reviewers, ever.
The paper also has something I haven’t seen before: a video abstract on youtube. It’s a great idea in principle — scientists ought to be able to describe the gist of their work in a few minutes on camera, in addition to a short paragraph at the start of their papers. But this theory…! Jebus. Here you go.
Just one excerpt that made me laugh: he uses an onion for a demonstration.
Here I have an onion. And let’s suppose that this is your DNA. An onion has layers.
Does DNA have layers? Is that supposed to be a nucleus? Can you do anything to demonstrate the appropriateness of your model to the thing you are modeling? No.
But Lineweaver goes on to pull out a knife and gently chop at and then hack bits off the onion. Oh, look, when he makes a desultory chop, it only cuts through the outermost layers, and as a final a-ha, he slices it in half to show that…
Outside has been damaged but inside is still intact.
But…but…but the processes that generate mutations, and that propagate such mutations through a population, are not restricted to only changing genes in reverse sequential order of their origin! Their proposed mechanism has no relationship to reality.
They then go on to propose a treatment strategy, in the vaguest possible terms, for dealing with cancer by targeting its weaknesses (that is, more recently “evolved” genes) rather than its strengths (phylogenetically older genes). But why should you even think older genes are somehow protected, or more difficult to target, either by mutations or cancer treatments? This isn’t an onion. We are looking at, for instance, signal transduction pathways, in which all levels are open to change…and we know that all levels can be modified by cancer. No “layers”, as Lineweaver proposes.
There simply isn’t a story here. No, cancers aren’t running off of an intact, ancient unicellular program.
For instance, two genes that are commonly damaged in cancers, with an extremely high frequency, are src and ras. They’re the core of the onion, if we have to persist with Lineweaver’s bad analogy, and they’re really, really old. From a paper by Hughes (1996) (note that it’s 18 years old — it’s not as if this is a surprising new revelation):
A phylogenetic analysis of src-related protein tyrosine kinases (PTKs) showed that one group of these genes is quite ancient in the animals, its divergence predating the divergence of the diploblast and triploblast phyla. Three other major groupings of genes were found to predate the divergence of protostome and deuterostome phyla.
Here’s a more recent one by Rojas et al. (2012), on ras:
New genomic information and the improvements to phylogenetic tools have further advanced our understanding of the structure and organization of the Ras protein superfamily. These advances are evident when comparing the current superfamily tree with that initially proposed 20 years ago (Valencia et al., 1991). It is now clear that the separation of the five main families (Ras, Rho, Arf/Sar, Ran, and Rab) was an early evolutionary event that predated the expansion of eukaryotes.
Lineweaver and Davies are disgraces, trading on a reputation in astrophysics (these guys aren’t biologists) to pollute the cancer literature with rank garbage. I really don’t know how they can get published in respectable journals.
Hughes AL (1996) Evolution of the src-related protein tyrosine kinases. J Mol Evol 42(2):247-56.
Lineweaver CH, Davies PCW, Vincent MD (2014) Targeting cancer’s weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model.Bioessays 36(9):827-835.
Rojas AM1, Fuentes G, Rausell A, Valencia A (2012) The Ras protein superfamily: evolutionary tree and role of conserved amino acids. J Cell Biol. 196(2):189-201.