Nobel Prize time

Well-earned prizes have just been awarded for milestone research on DNA Repair. To quote from the Independent as usual (only because it’s cheap) the contributions of the three winners was as follows:

In their announcement, the committee described how Lindahl “demonstrated that DNA decays at a rate that ought to have made the development of life on Earth impossible”. “This insight led him to discover a molecular machinery, base excision repair, which constantly counteracts the collapse of our DNA.”

Sancar was recognised for his work on “nucleotide excision repair, the mechanism that cells use to repair UV damage to DNA”. That has helped with the treatment of skin cancer, since people born with defects in that repair system will develop skin cancer from being exposed to sunlight. “The cell also utilises nucleotide excision repair to correct defects caused by mutagenic substances, among other things,” the committee wrote.

Modrich’s work demonstrated how the cells corrects errors that occur while DNA is being replicated. “This mechanism, mismatch repair, reduces the error frequency during DNA replication by about a thousandfold,” the committee wrote. “Congenital defects in mismatch repair are known, for example, to cause a hereditary variant of colon cancer.”

Let’s quickly list this work’s utility to the scientific enterprise:

Extends and deepens our knowledge of the natural world
Has practical application, in this case in life-saving medical advances
Confirms the paradigm of purely efficient, ateological material causes in science X
Confirms the ruling paradigm of Neodarwinian evolution in biology X

So, big success on the “detail” front – a couple of problems with the “big picture”. Let’s look at the latter.

As soon as you talk about “repair”,  just as is the case with “redundancy” , you have entered the world of final causes – teleology. You are talking about a standard, outside the physical structure being repaired, to which it is to be conformed – a target in other words. And goal-setting requires an explanation.

One headline about the Nobel award spoke about “DNA repairing itself”. If one is talking about DNA in terms of separate genes or gene-units, that’s crazy talk – the DNA repair system, assuming it’s entirely gene-based, needs to be intact to work itself, so it could not logically repair itself.

So that headline appears to be suggesting that the genome acts as a single unit, “The DNA” of which one part (the correctly sequenced DNA repair kit) obligingly repairs another part (the broken sequence). That in itself is problematic, for it suggests (a) there is a single indivisible entity, the genome, which would reintroduce the forbidden (and unexplained) idea of form and formal causation. “The DNA” would be another way of saying “The Soul”. Additionally (b) this entails that there is a “norm” or “target” not actually present in the genome itself, towards which the repair process tends. If your assembly program arose in an unplanned fashion, who saved a “correct” version with which it may be compared?

Now, perhaps one might suggest that this target is simply the pre-error sequence, the “last good configuration” on which the repair system operates something like a checksum. But that actually makes not a scrap of difference: something has decided that the “is” of the particular gene sequence has become an “ought”, and “ought” = “final causation”. Like “METHINKSITISLIKEAWEASEL”, such a template is a teleological element that excludes any possibility that the process is truly undirected, except unlike the latter, DNA repair doesn’t make any Dawkinsian pretensions about being an example of the power of randomness – it looks designed anyway, as any honest workmanship looks designed.

Although, ostensibly, the whole thing has been brought into existence by evolution, what has evolved is a very efficient tool for preventing evolution in most cases, and extinction in very many more.

The second big problem in this matter is its effect on the plausibility of Neodarwinian processes (or any other material process we have to hand). Remember that quote from the committee:

Lindahl “demonstrated that DNA decays at a rate that ought to have made the development of life on Earth impossible”.

Here’s the issue: DNA is actually a very unstable molecule. Under ideal conditions, it survives <1m years. Conditions are seldom ideal even now, let alone at the dawn of life, and life requires complete survival of the sequence if one of evolution’s non-negotiable conditions – inheritance of characters – is to be fulfilled. In order for life to develop and evolve you need, and Lindahl has uncovered, “a molecular machinery, base excision repair”. So how, even in principle, is such a complex machinery going to evolve using unstable DNA?

Perhaps, one might wonder, it all happened so long ago (as it must have done for life to get off the starting blocks) that it was a product of the hypothetical RNA world, only later adapted to deal with the unstable chemistry of DNA. But what won’t work with DNA is even less possible with RNA:

While DNA contains deoxyribose, RNA contains ribose (in deoxyribose there is no hydroxyl group attached to the pentose ring in the 2′ position). These hydroxyl groups make RNA less stable than DNA because it is more prone to hydrolysis. https://www.quora.com/Why-is-DNA-stable-but-RNA-is-not

Eugene Koonin felt the need to enlist the multiverse to load the odds sufficiently for DNA replication to have a snowball’s chance in hell of evolving. It’s a good trick to invoke infinite possibilities, because it covers at one bound the extra orders of magnitude required for DNA repair also to evolve within the geological instant it takes for DNA to break down naturally:

Scientists have estimated that under the most ideal conditions, DNA can theoretically survive for a maximum of one million years.

That, of course, ignores replication errors. And the fact that conditions usually aren’t ideal. And that one isn’t supposed to set evolution particular targets and timescales, because it lacks any ambition. If we dismiss the multiverse hypothesis, some would call it a miracle.

Jon Garvey

About Jon Garvey

Training in medicine (which was my career), social psychology and theology. Interests in most things, but especially the science-faith interface. The rest of my time, though, is spent writing, playing and recording music.
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11 Responses to Nobel Prize time

  1. Sy Garte Sy Garte says:

    Jon

    I fully agree with your comments about early life and abiogenesis, and I have come to believe in panspermia. Like Koonin, I find the idea that LUCA complete with DNA and all its attendant machinery, developed (evolved doesnt seem to be the right word) in a few hundred million years, untenable.

    As for the DNA repair story, I must say I need to think about this some more. I have been working on various aspects of DNA repair for over 30 years, (I know Lindahl) and have come to just accept it as an obvious, natural part of cell biology. That includes the idea of a straightforward evolution of repair pathways (which can be highly complex, as you imply) selected for to avoid death. Here we are close to the previous discussion on redundancy.
    I have not given much thought to the philosophy behind such acceptance. You make a very good point concerning which version of any genome is the one that is the selfish gene, as compared to just “the bad gene” or the “wrong” gene. This is also the case when looking at various alleles, which eventually lead to evolution. If a gene is trying (through natural selection, of course) to remain a survivor, and to do so it must mutate, is it still the same gene? And if it isnt, then who do we define what a gene is, if not by its sequence.

    I agree that neo Darwinism is in its death throes, because it just cant explain very much anymore. (There are a series of posts on this on my blog). I am very excited at the real possibility that what replaces it might very include some aspects of teleology as scientifically valid in the evolution of life.

    • Sy Garte Sy Garte says:

      Sorry for all the typos, I have gotten used to editors on web sites. I will proofread better next time.

      • Jon Garvey Jon Garvey says:

        Forget typos – it took me half a dozen goes to get a bit of HTML right to correct a comment this morning… but then, I had a target to aim at 😉

        If Neodarwinism is indeed on the rocks, I think one of the first things to go will be the selfish gene metaphor, which seems to me utterly confusing in an ateological scenario, and to identify the least likely “teleological entity” in a teleological one.

        But the definition of “gene” has become most unwieldy, not to mention controversial, and will I think continue to be in flux until it either means something very different or is quietly dropped as a concept.

        After all, if we take Noble’s physiological and naturalistic version of teleology, it appears to depend on everything interacting with everything else as one unit, the organism. In such a scheme, “gene” is just a crude label for segments of an irreducible global process.

        And it seems to me,most robust versions of a divinely-contrived teleology would also envisage that “global interdependance”, which would of course imply that God had built in some degree of self-motivation to living things qua living things.

        The really interesting science, though, if the day comes when teleology takes its place at the biological table, will be to allocate the extent of its role. If organisms are goal setters, there’s less pressure to account for everything by passive natural selection – they may behave in a certain way because they perceive a certain goal, not because certain random behaviours proved beneficial in the past. Or they may edit their genomes in search of specific aims (as per James Shapiro), thus contributing actively to their own adaptation, in which case how do they “choose” their target?

        And if they do influence their own evolution in that way, do they just do fine tuning, or did LUCA just have the “will”, in some Lamarckian sense, to seek its survival through all the forms we now see – much as you conjecture about selfish genes in your comment… only it seems to me intrinsically more plausible for a complex self-contained organism and its offspring to pull itself up by its bootstraps than a short length of DNA whose boundaries can’t really be identified.

        But all that’s just day-dreaming on my part: it’ll be you guys who both make the discoveries and, perhaps, redefine the paradigms. Exciting days – I’ll begin to go for panspermia if they find some separately evolved bacteria on Mars.

  2. GD GD says:

    Fascinating work by three scientists, and spanning many years – I liked the way the statement mentioned many other scientists and their work that contributed to this. I note Jon, that the statement released on with the Noble Prize announcement, included a notion that this is another reason for Darwinian evolution. I take this to mean the commitment by many scientists to this evolution is profound – even when the scientific insights make it appear implausible.

    For what it is worth, I am of the view that we are just too far removed from the correct notions to be able to scientifically discuss how life began – the notion that life coming from outer space, has also had a very bumpy ride. To illustrate this point, I will mention a paper that examined meteorites for organic molecules – I was amazed to note the meteorites examined had travelled through an atmosphere teeming with all sorts of molecules, had become molten, and had plunged into earth that is filled many molecules – yet the paper made a glancing comment on this, and went of showing organic fragments in the meteorites MUST have originated from outer space. If such work was not underpinned by an almost pathetic need to believe Darwinian outlooks, I am certain the same authors would have made great effort to either show which molecules were from the earth, or most likely, conclude that they were unable to decide where such molecules came from, but they were likely derived from the earth.

    My point has more to do with seeking reliable, and believable science – when we depart from this, it should be regarded as speculation – in the case of evolution, it is beyond speculation and more in the realm of unsupported belief. An unfortunate aspect of all of these criticisms is the absence of a general theory that would place such excellent work within a framework that enhances our appreciation of the insights from the natural sciences.

    • Jon Garvey Jon Garvey says:

      Hi GD

      Yeah – Sy’s panspermia would, on a naturalistic basis, simply push the unexplained genesis of life back to some unknown time and place (or leave it in the multiverse, if Dembski’s work on the universe’s lack of combinatorial resources stacked up), and add the mystery of a foolproof transport system across the galaxies.

      On the other hand, supposing life were found to be as basic a component of the universe as matter? ie “panspermia” in the same sense as “panmolecularia”? That would set the cat among the evolutionary pigeons again, wouldn’t it? Like finding coffee machines waiting on every panet you visited, still with no plausible origin!

      • GD GD says:

        Hi Jon,

        I am an avid sci-fi fan and have commenced a sci-fi novel, but I admit I had not thought of coffee machines in outer space – I like the way you think. Perhaps a few more ideas from you and I should have little trouble finishing this novel.

        I am all for letting one’s imagination loose – but I use terms such as sci-fi for this – merely a preference of mine.

        • Jon Garvey Jon Garvey says:

          But just imagine how the cafeterias would be taken for granted after a while.

          There’s be expeditions enduring untold hardships in the fruitless quest for life, with the only consolation being that at least you could get a decent cup of coffee wherever you roamed.

          • GD GD says:

            “A decent cup of coffee!” Surely thou jest (but wait, this is fiction). I did boast many years ago to have made and drunk such a cup, but I was young, foolish, and on ‘my own’, so I guess I may have (in a random manner) achieved the production of said cup. Now I imagine it (and me thinks the space crew who endure may believe at the end there will be that “decent cup” waiting for them).

  3. pngarrison says:

    “You are talking about a standard, outside the physical structure being repaired, to which it is to be conformed – a target in other words. And goal-setting requires an explanation.”

    I don’t understand your assertion that an external standard is implied. DNA repair works by using the sequence of the undamaged strand as its information source for the repair, or in some recombination-based modes of repair, a very similar sequence elsewhere on the chromosome or on another chromosome becomes the source of the repaired sequence. There is no “ideal” sequence that the process shoots for. There is only the sequence that remains on the undamaged strand or elsewhere in the genome.

    In fact, many of the enzymes that work in DNA repair are less accurate in copying the sequence being used as a template than the usual replicative enzymes, and so DNA repair is in actually often somewhat error prone even when it is working correctly.

    • Jon Garvey Jon Garvey says:

      Preston

      My contention is that a system that recognises “damage” is by that very same token aiming at “non-damage”. That the mechanism takes its pattern from the previous sequence or one like it doesn’t alter that. It doesn’t replace the sequence at random or from some other variant source. It is teleology therefore – the question of whether, in principle, such teleology could arise by ateleological processes is a separate issue.

      The fallibility of the error-correction is common to all such systems – indeed, all systems – even human ones, so shouldn’t have a bearing on teleology, unless because, since it is what, presumably, permits limited evolutionary change, even the remaining error-rate could serve a function.

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