Goodbye to the blind watchmaker — take I

The Michelson and Morley experiment destroyed the ether paradigm in 1887, but its replacement didn’t occur until Einstein’s special relativity in 1905.  One can disagree with a paradigm without being required to come up with something to replace it. Unfortunately, we tend to think in dichotomies, so disagreeing with the blind watchmaker hypothesis for life itself tends to place you in the life was created by some sort of conscious entity.  “Hypotheses non fingo”  (Latin for “I feign no hypotheses”) which is what  Newton famously said  when discussing action at a distance which his theory of gravity entailed (which he thought was pretty crazy).

Here are  summaries of four previous posts (with links) showing why I have problems accepting the blind watchmaker hypothesis.  These are not arguments from faith which nowhere appears, but deduction from experimental facts about the structures and processes which make life possible. Be warned.  This is hard core chemistry, biochemistry and molecular biology.

First the 20,000 or so proteins which make us up, a nearly vanishing fraction of the possible proteins.  For how vanishing see —  Just start with 20 amino acids, 400 dipeptides, 8000 tripeptides.  Make one molecule of each and see how long a protein you wind up with making all possibilities along the way.  The answer will surprise you.

Next the improbability of a protein having a single shape (or a few shapes) for some chemical arguments about this — see

After that — have a look at

The following quote is from an old book on LISP programming (Let’s Talk LISP) by Laurent Siklossy.“Remember, if you don’t understand it right away, don’t worry. You never learn anything, you only get used to it.”   Basically I think biochemists got used to thinking of proteins have ‘a’ shape or a few shapes because that’s what they found when they studied them.

If you think of amino acids as letters, then proteins are paragraphs of them, but to have biochemical utility they must have ‘meaning’ e.g. a constant shape.

Obviously the ones making us do have shapes, but how common is this in the large universe of possible proteins.  Here is an experiment which might show us (or not)–

From a philosophical point of view, the experiment is quite specific.  From a practical point of view quite possible to start, but impossible to carry to completion.

Well this is a lot of reading to do (assuming anyone does it) and I’ll stop now (although there is more to come).

Why do this at all?  Because I’ve been around long enough to see authoritative statements (by very authoritative figures) crash and burn.  Most of them I didn’t believe at the time — here are a few

l. The club of Rome’s predictions

2. The population bomb of Ehrlich

3. Junk DNA

4. We are 98% Chimpanzee because our proteins are that similar.

5. Gunther Stent, very distinguished molecular biologist, writing that we were close to the end of our understanding of genetic biology.  This in 1969.

The links elaborate several reasons why I find the Blind Watchmaker hypothesis difficult to accept.  There is more to come.

“Hypotheses non fingo”

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  • Peter Shenkin  On February 18, 2019 at 1:37 am

    2. More impressively, make that the population bomb of Mathus.

  • Peter Shenkin  On February 18, 2019 at 2:09 am

    I did a post-doc with Cy Levinthal. Cy’s “solution” to his paradox (the paradox being that it would take longer than the age of the universe for a medium-size protein to sample all its torsion angles even at medium resolution in order to find its thermodynamic minimum) was that the native state of a protein must, or at least might, be kinetically determined; i.e., maybe it’s not the thermodynamic minimum, but rather the local minimum that is found most quickly. That begs your question of why there should be a dominant stable minimum at all, or (stated differently) how it is that the very sparse subset of proteins exhibiting such a minimum gets selected for in a given origin-of-life scenario.

    But just to continue with the Levinthal paradox for a moment, I feel the paradox has a flaw. Namely, self-avoidance of the polymer chain makes all but a very small part of that conformational space physically inaccessible. It may not be the case that there’s not time to sample the space; rather, the physically accessible part of Cy’s space is so much smaller than the space he cites that it may be accessible temporally.

    But this still begs the question why proteins should have a unique minimum, global or kinetic for that matter. I would agree that most don’t. But it would seem that given enough hydrophobic residues, distributed so as to cause a collapse into a somewhat globular shape, many will have at least a bunch of compact conformations, and some will have a strongly dominant conformation or family of micro-conformations.

    Cy questioned whether even those proteins known to have a strongly dominant conformation were at their thermodynamic minimum. I’d guess that many are; some are known not to be; like maybe prions. I say “maybe”, because I don’t know enough about prions to be sure, since the situation appears to be confounded by the role of aggregates, as in sickle-cell anemia.

    Anyway, I don’t have answers; but think about the above.

  • luysii  On February 18, 2019 at 12:34 pm

    Thanks. I’m not a polymer chemist, but I play chamber music with a retired polymer chemistry prof. I’m pretty sure that chain self avoidance has been worked out. I’ll ask him the next time we meet. There is an incredibly elegant example of how the rate of transcription determines the conformation of two forms of cytoplasmic actin (beta and gamma), allowing the cell to have different amounts of them (despite differing in only 4 or 300+ amino acids.

  • Peter Shenkin  On February 19, 2019 at 1:43 am

    Ash goes back and forth on reductionism in the blog entry you quote. I do think that reductionism is all we have as scientists; we explain one behavior at a time based on the parts that most conveniently and usefully define something. The quotation of Dirac at the end makes a lot of sense to me, as does Weinberg’s differentiation between reductionism in practice and reductionism in theory. We use the tools and methodology that are most useful for a given problem, and then we encounter problems we can’t solve, sometimes clever people solve them with the tools we already had and sometimes the problem is reconceived and new tools, or even new deep concepts (redefining the parts we use) are brought to bear.

    In the quantum realm, quantum calculations are used on a daily basis, not only to predict / discover things about bonding behavior, but also to parametrize forcefields used in simulations involving millions of atoms, some of which give useful results. Ultimately, there is some sense in which, to the extent that QM is valid for everything (which is not 100%), there is one wave function that describes the entire universe, not separate ones for each molecule. But the only tools we have for use in computational quantum chemistry on a production basis involve computations of wave functions for small systems, checking that derived parameters give good results in molecular mechanics on medium-size systems, and then running with them on large systems, all the time trying to improve our methodology. For organic molecules, you usually do not have to include relativistic effects, and nowhere in this process do you have to consider quarks, or even, as far as I know, the radius of a nucleus.

    You’re quite right to point out the existence of so many secrets of the cell whose etiology we don’t understand and whose behavior is in many ways surprising and mysterious and beyond anything we would have predicted. The latest is these micro-droplet phases in the cell which appear to undergo phase transitions and defy our notion that the inside of a cell is like the inside of a test-tube, just smaller. I do think we will be able to understand, manipulate, and make use of such behaviors, but not necessarily figure out how and why they are there; and I’m sure there are plenty of equally surprising behaviors yet to be discovered. One might ask whether we’ll get to the end. I’d answer, “Of course not!”

    My father used to sing me a nursery rhyme:

    Oats, peas, beans and barley grow,
    Oats, peas, beans and barley grow,
    Do you or I or anyone know,
    How oats, peas, beans and barely grow?

    I’d answer “No”, unless one uses a limited observational and functional definition of “How”.

    For me, reductionism is a tool, not a theory, and I’m not so interested in philosophical questions concerning things like whether the universe is in some sense theoretically explicable using reductionist principles. Philosophically, I think it suffices for scientists to be ambitious but suitably modest about what our reductionist practices can accomplish, but I think those are the only kind of practices we have.

  • Visitor 45  On February 19, 2019 at 7:41 pm

    I can imagine a blind watchmaker evolving a man from a microbe, but I have a lot more trouble imagining how geochemistry evolved into a microbe.

  • luysii  On February 19, 2019 at 10:33 pm

    Peter: Thanks. I’ve always thought that ‘the wave function of the universe’ was a crock — what do you write it down on?

    The microdroplets are going to be huge. As far as I’m aware they were totally unpredicted by theory of any sort. You might be interested in the following post —

    I wrote the author of the article cited in the post and got the following back 12/18

    Excellent post! Revolution happening here. Just hosted a small meeting of physicists, chemists and biologists to share thoughts about this new field of soft matter biophysics. Stay tuned.

    Did your family ever summer on Long Beach Island N. J ?

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