Cancers aren’t atavisms!


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.

Comments

  1. nomadiq says

    What is it with people making geometric arguments? DNA is like an onion… not. It isn’t a sphere. There are not genes that are more “protected” because they are at the ‘center’. It has no resemblance to the reality of how DNA is actually situated inside cells.

    It reminds me of Sam Harris’s argument last week saying that at the ‘center’ of Islam there are terrorists, then a layer around them he called jihadists. Its a cute way to geometrically describe a ‘reality’ but unfortunately that language ends up making you think about a problem the wrong way.

    Same for DNA, same for terrorism. These simple models are just leading people down the wrong path to solutions.

  2. Amphiox says

    So I guess the spherical cow in the vacuum has onion shaped DNA in its atavistic cells.

    And that spherical shape is also an atavism from the Volvox-like colony stage!

  3. carlie says

    Jesus. That onion analogy sounds like something someone would come up with when they’re high.
    “Did you ever look at the inside of an onion? I mean, really look at it?”

  4. Becca Stareyes says

    I just think of that scene from Shrek with the onion analogy. So DNA is also like an ogre. (Does DNA make you cry?)

  5. Athywren says

    Does he give lectures? Does he give lectures like this? Why is his script on screen? I can’t speak to the value of his ideas, as I’m not a biologismist, but it kinda seems like either he or much of the visual element of his video is redundant here.
    The graph was interesting, but would’ve been better if it filled the screen, rather than being squished to the side and still hidden behind him when he went to swish his hand in a way that could easily have been done by highlighting or with the bracketing that they used a moment later – that way we could actually read all of the writing without expanding the video.
    He also probably would’ve benefited from a few extra takes, clear out the stutters and fumbles – I know it’s meant to be an academic video, but it’s still important to demonstrate a certain degree of mastery over the medium you’re going to use.
    And wtf is with bringing the onion into shot and chopping at it?! It’s a metaphor, and even if it applies, we can work out what you mean without needing a visual demonstration thank you very much. I cook with onions quite often, and I know that their outside layer is nearer to the outside than the inside layers are. I can work that much out. Am I being sensitive, or is that really as offensively condescending as I feel it is?
    That “ABC” diagram would have been interesting. It’s a shame I couldn’t make anything out other than pretty colours, the words ‘longest’ and ‘shortest,’ and his arm again. Its corresponding graph… again, I didn’t get much from it. I’m guessing that the colours corresponded to the same colours in the previous image? It would’ve been more useful if I could’ve seen more detail, and less of his arm. The final graph is just pissing me off now.

    FFS, if you’re going to use video for this purpose, use it well! I wouldn’t present a paper with graphs and images that I’d doodled over, and I wouldn’t put myself in front of them on video when I could use less intrusive tools within the video to highlight the parts I wanted to draw people’s attention to. I definitely wouldn’t use a loose metaphor as an instructional moment, because, as anybody who’s ever used a metaphor in an argument will tell you, they don’t hold up to close scrutiny. And I certainly wouldn’t condescend to the audience in such an instructional moment by demonstrating that not cutting completely through something doesn’t result in it being cut completely through. I’m actually angry about that.

    trading on a reputation in astrophysics (these guys aren’t biologists)

    *facepalm*
    I absolutely do not even.
    Are there any biologists out there, who don’t mind tarnishing their reputation a bit, who’d be willing to write a paper asserting that comets are derived from ice cream, and can sometimes be found to contain a chocolate flake? I know it’s not quite the same as proposing an idea based on discarded theories, but I really don’t want to find myself arguing with people about aether or phlogiston if anyone takes it seriously.

  6. Athywren says

    So DNA is also like an ogre. (Does DNA make you cry?)

    DNA makes me cry? But that’s because I’m allergic to a full understanding of biology – too squishy, too messy, too many residues.

  7. Crip Dyke, Right Reverend Feminist FuckToy of Death & Her Handmaiden says

    @nomadiq, #1:

    Same for DNA, same for terrorism.

    So you’re saying DNA is like terrorism? Quick, someone tell Dick Cheney and Shrub!

  8. sawells says

    I met Davies when I was at ASU and they were just setting up this ridiculous “beyond” centre. He wanted to literally nuke a hole in Mars to find out if there was life in the rocks underneath, and he had a guest speaker arguing that Deinococcus radiodurans had evolved to withstand living in meteorites while travelling between planets. Really embarrassingly bad quality of thinking.

  9. Crip Dyke, Right Reverend Feminist FuckToy of Death & Her Handmaiden says

    @Athywren, #6:

    I’m not a biologismist

    Wait, now DNA is like gism?

    How do we fight this scourge of onion-breathed terrorist gism?

  10. Richard Smith says

    @Becca Stareyes (#5)

    Actually, DNA is like a parfait. Everybody loves parfait. If you don’t eat all of your parfait, you’ll get cancer!

  11. Crip Dyke, Right Reverend Feminist FuckToy of Death & Her Handmaiden says

    @sawells:

    he had a guest speaker arguing that Deinococcus radiodurans had evolved to withstand living in meteorites while travelling between planets. Really embarrassingly bad quality of thinking.

    Yes, well it’s better than the theory that Davies came up with later, which was that Deinonychus radiodurans engineered the K-Pg extinction after evolving to withstand living in meteorites while traveling between solar systems.

  12. Athywren says

    @Crip Dyke, 11

    I’m not a biologismist

    Wait, now DNA is like gism?

    A biologismist is a follower of the religion of biologism! :P
    That said, from what I know of the two substances, I would expect DNA to be at least a little bit like gism, at least in sufficient quantities to be visible.
    Did I just demonstrate quite how not a biologist I am? I suspect I did….

  13. Ariaflame, BSc, BF, PhD says

    *sighs* While I’m not quite going to go #notallphysicists I full acknowledge that where people fall down in science is when they try to work outside their field without doing their damn research. Including learning the basics first. So as a physicist, sorry… I myself do not pretend to know terribly much about biology.

  14. drst says

    Howard Bannister @ 10

    Parfait is like onions; parfait has layers.

    And everybody likes parfait!!

    And in the morning, I’m making WAFFLES!

  15. Amphiox says

    I have to wonder if these authors even bothered to review the recent cancer literature. Because the current understanding of cancer is that they aren’t merely random collections of aberrant mutated individual cells. They are aberrant organs, with hierarchies of differentiated tissue types within them. They recruit their own blood supply and maintain their own self-supporting micro-environments. IE the cells in tumours cooperate together to grow, spread, resist treatment and thwart host immunity. And they have cancer STEM CELLS as cells of origin.

    Last I checked, single called organisms do not grow into organs, aberrant or otherwise, and they don’t arise from stem cells.

  16. Amphiox says

    In other words, far from being atavisms of the unicellular state, cancers are derived from multicellular adaptions.

  17. Kevin Kehres says

    When I first started reading this, I made the following prediction:

    “I’ll bet these guys do not have any scientific grounding in cancer biology at all.”

    Glad to see my powers of precognition are intact.

  18. Markita Lynda—threadrupt says

    Ogres have layers!!!111 eleventy!

    Seriously, what’s their mechanism. DNA is constantly renewed and remade, not passed down like a kernel in a nut.

  19. sawells says

    What bugs me particularly is that I actually am a physicist trying to do something useful in the biological field (modelling protein flexibility and rigidity), and stuff like this does NOT make it easier to get taken seriously. Mutter grumble.

  20. azhael says

    This morning i saw a youtube video about a horrible person lying to others about how wheatgrass is so healthy and so good it actually allows cancer to be cured (no, it doesn’t cure it, it allooooows it to be cured)..and now this…No, this is not a good way to start the weekend….
    There is so much wrong in everything they say that a part of me would like to think that anyone would be able to smell the horseshit within the first few seconds…unfortunately i know that’s not true…

  21. Menyambal says

    I identify as an engineer, and even I know these guys are wrong. DNA is not like an onion. Maybe a chain, or a coded chain, but not an onion.

    Amphiox @ 18. Thanks for that nifty description. That makes all kinds of sense.

  22. dannysichel says

    “Kragar says that life is like an onion, but he doesn’t mean the same thing by it that I do.

    He talks about peeling it, and how you can go deeper and deeper, until finally you get to the center and nothing is there. I suppose there’s truth in that, but in the years when my father ran a restaurantcured people’s cancer, I never peeled an onion, I chopped them; Kragar’s analogy doesn’t do much for me.”

  23. unclefrogy says

    isn’t that like the explanation from science fiction we see some times when so alien organism invades a human body then turns it into a new alien monster of some kind even doubling in size without having to even eat anything or being exposed to “Gama rays”

    it would be nice if reality was all linear and clear and simple and not all wiggly and directionless.
    uncle frogy

  24. Athywren says

    @dannysichel, 27
    “Kragar” is a name that demands to be followed by “the destroyer.”

  25. Anton Mates says

    @Crip Dyke

    Deinonychus radiodurans

    or, as it is more commonly known, “Godzilla.”

  26. F.O. says

    Fuck.
    The antics of these imbeciles aren’t harmless.
    At best they remove resources from real cancer research… WTF!

  27. Lofty says

    He’s explaining onion based genetics to employees who haven’t yet graduated to food prep at their local burger chain.

  28. Rich Woods says

    @Lofty #33:

    He’s explaining onion based genetics to employees who haven’t yet graduated to food prep at their local burger chain.

    And the employees have concluded that the best way to cure cancer is to chuck it in a deep fat fryer.

  29. naturalcynic says

    I’m not only astounded by the amateurish presumption of biological coherence but also by the mechanics of the presentation. It’s [or should be] embarrassing. There are so many places where another take would have made it smoother. It’s not like he just had to do it all in one seamless take like some lecture or play.
    Lineweaver gave a much better TEDx presentation about cosmology and human intelligence [and presumptiousness] that he should have reviewed. A little personal humility would have helped a lot. He’s still goofy, but in the TEDx talk it doesn’t detract nearly as much.
    Just another example of a soi disant polymath failing.

  30. Ichthyic says

    Here I have an onion. And let’s suppose that this is your DNA. An onion has layers.

    Onions have layers… ogres have layers.

    It’s the Shrek theory of cancer biogenesis.

  31. Amphiox says

    It is like an onion in that trying to examine the metaphor in any detail makes one weep….

  32. chris61 says

    I think you’re missing the point but I could of course be wrong. I suppose the real test will be if this kind of thinking inspires the development of better cancer treatments.

  33. Ichthyic says

    I suppose the real test will be if this kind of thinking inspires the development of better cancer treatments.

    no…. how science is usually done is that there is a plausible mechanism hypothesized first.

    what’s the plausible mechanism here, based on what biologists already know?

    it doesn’t exist. which is why seeing NIH funding go to something like this seems… fishy.

    and I know fish.

  34. says

    Is this a form of agency gone really bad. As delicate, mortal creatures, we have a bad tendency to find an agent behind things that simply happen. Somehow believing someone is behind bad things makes us less scared than simply bad things happening. Well is atavistic belief any different? Now cancer doesn’t just kill us; no, it is a less evolved selfish creature looking out for its interests. Well we all get why a life being would be selfish. So does this make cancer less scary? To me it makes it more alien invasion like and hence much scarier.

  35. chris61 says

    @41 Ichthyic

    The plausible models of how best to treat cancers that can’t be cured by surgery have not proven to be all that successful. For most later stage and aggressive cancers chemotherapy only temporarily slows cancer growth. So there might be a plausible mechanism in this kind of thinking if one doesn’t take the model too literally.

  36. Nerd of Redhead, Dances OM Trolls says

    So there might be a plausible mechanism in this kind of thinking if one doesn’t take the model too literally.

    And where would that be? If you mean “thinking outside of the box”, but being realistic, that is what good scientists do. This smells of scientific bullshit without any redeeming features.

  37. chris61 says

    @44 Nerd

    And where would that be? If you mean “thinking outside of the box”, but being realistic, that is what good scientists do. This smells of scientific bullshit without any redeeming features.

    Sometimes even good scientists need a little help to think outside the box. You may be right and this has no redeeming features but I prefer to withhold judgement for a few years to see what, if anything, comes of it.

  38. azhael says

    Even if there was anything whatsoever worth exploring in the idea that using antibiotics could be of some benefit for treating cancer, you are not going to find out by giving money to these morons who think that DNA have layers and that the deeper ones correspond to the genomes of ancient organismal forms….
    These people don’t know shit about what they are talking about, they are just making shit up based on their horribly inadequate and extremely wrong “understanding” of biology. This is not thinking outside the box, this is known to be utterly false horseshit. Like someone else said earlier, this is at the level of shit you make up about a subject you know absolutely nothing about when you are high out of your fucking mind.

  39. Athywren says

    Bearing in mind that I know next to nothing about biology and may be talking utter shit, don’t we have a bit of a problem regarding bacteria becoming resistant to antibiotics at the moment?
    It seems as if pursuing an antibiotic treatment for cancer, when we already have that problem on the horizon with antibiotics and when biologists are saying that it doesn’t have any prior plausibility, would end up being simply another cause of antibiotic resistance?

  40. says

    Athywren:

    It seems as if pursuing an antibiotic treatment for cancer, when we already have that problem on the horizon with antibiotics and when biologists are saying that it doesn’t have any prior plausibility, would end up being simply another cause of antibiotic resistance?

    Maybe that’s the point: but the patient died from a staph infection, not the cancer, triumph!

  41. chris61 says

    Azhael @ 46

    Even if there was anything whatsoever worth exploring in the idea that using antibiotics could be of some benefit for treating cancer, you are not going to find out by giving money to these morons who think that DNA have layers and that the deeper ones correspond to the genomes of ancient organismal forms….

    Why I said I don’t think the model should be taken literally. I don’t for a moment think that using antibiotics would be of use for treating cancer nor do I think DNA has layers.