@bjmiller I’m still confused on what your goal is here. Can you clarify your aims? What is different about your contribution here? What are you try to add to the work of, for example, Meyers, Tour, and Bradley? Meyers was not convincing. Where do you think he went wrong and how are you fixing it?
Some really exciting developments will be coming over the next year, so stay tuned. No spoilers for the moment.
And, have a wonderful New Year.
Hi Dr. Miller,
I hope you had a happy New Year. Thank you very much for your revised calculation. I’d just like to offer a couple of brief comments, for what they’re worth. In your original calculation, you wrote:
Here is the start of a quick calculation of probabilities. First, producing an AA chain would require homochiral AAs to form peptide bonds of sufficient length. I will make several very generous assumptions:
- Average AA length for enzyme which could couple two reactions is assumed to be 100.
- The chance of a chain of any given length adding a new AA as opposed to breaking apart is assumed to be 80%, so chance of forming 100 unit chain is (.80)^100.
- Starting mixture is assumed 80% homochiral with L-AAs, so the probability for only L-handed AAs forming 100 unit chain is (.80)^100.
- The probability of two AAs forming peptide bond as opposed to an alternative bond is 80%, so the chances of 100 AAs forming right bond is (.80)^100.
The chance of a chain forming which is a candidate for a functional enzyme is then
P = (.80)^100 * (.80)^100 * (.80)^100 which is roughly 1 in 10^29
In your revised calculation, you propose a more realistic estimate:
…[T]he situation is actually far worse that I described. All OOL experiments which yielded multiple amino acids also produced several other byproducts in greater total abundance than nearly all of the AAs. As a result, the possible number of bond types formed in any realistic scenario would be quite large. Therefore, my estimate of 80% for forming the alpha-peptide bond is very likely over an order of magnitude too high [in other words, the true figure is about 10% rather than 80% (VJT)]…
A recent article reviewed experiments attempting to generate polypeptides, and it described how the proportion of chains in all circumstances drops off exponentially with length as described by the Flory–Schulz distribution. Based on this equation, the authors estimated that the proportion of chains 40 units in length would have been 1 part in 10 trillion [= 10^-13 (VJT)]…
Let me repeat my calculation with more realistic numbers. I will assume a chain of 40 AA in length, so I will use the 1 in 10 trillion figure. And, I will assume a solution of molecules matching the output of the most successful OOL experiment based on the most likely conditions. I will also combine the probabilities of the right bond forming for any given AA with another AA, as opposed to another molecule, and that associated with the homochirality condition. As a result, I will drop my estimate of [the chance of] an L-AA bonding to another L-AA with an alpha-peptide bond to 10%. My calculation for a candidate chain then becomes the following:
P = (.10)^40 * 10^-13 = 10^-53 (i.e. clearly implausible)
I am not a scientist, but I’d just like to point out that your calculation is highly sensitive to the value of the probability of an L-AA bonding to another L-AA with an alpha-peptide bond. You believe it’s likely to be no more than 10%, and you may well be right. But if it were 20%, then P would be (.20)^40 * 10^-13 = 10^-41, which is well above 10^-50 (the cutoff figure used in Borel’s law). And if the probability in question were 30%, then P would be (.30)^40 * 10^-13 = 10^-34, which is even higher. In other words, while it’s very unlikely, on the primordial Earth, it just might have happened - and in a universe with 5 * 10^21 habitable worlds, the chances that it would have happened are much higher. Thus a skeptic could concede that the odds of life appearing somewhere in the cosmos are low, but not astronomically low.
Nearly all OOL scientists would fully acknowledge that the proportion of configurations of molecules forming life to non-life is too small for nature to stumble upon life by chance. For instance, Eugene Koonin estimated that the likelihood for the simplest translation mechanism from RNA to proteins based on ribozymes forming was 1 in 10^1000. The actual process of translating from AA sequences in a protein to RNA and then back to a protein using the same code would have been much more difficult.
I believe Koonin’s calculation is flawed. In his article, “The Cosmological Model of Eternal Inflation and the Transition from Chance to Biological Evolution in the History of Life” (Biology Direct 2 (2007): 15, doi:10.1186/1745-6150-2-15), Koonin begins by declaring: “Let us assume that, for the onset of biological evolution, a unique n-mer is required.” However, it is pure speculation on Dr. Koonin’s part to assert that a unique n-mer was required in order to produce a coupled replication-translation system. Koonin’s initial assumption is therefore almost certainly false. It is much more likely that many different n-mers would do the job equally well. Also, from what we know of RNA structure, it appears that there is a combinatorially large number of RNA sequences which adopt the same structure, and thus there is no reason why this magic sequence should be any different.
Another criticism that can be made of Koonin’s calculation is that it merely rehashes common objections to current RNA-world models, noting that if they were valid, then the emergence of a system capable of further evolution was astronomically improbable. I’m not a fan of such models, as I’ve stated above.
Do you know any reasons why these criticisms of Koonin would be invalid?
Finally, I’d like to address your remark:
The peptide-RNA scenario you mentioned requires highly coordinate reactions, and some would have been energetically unfavorable, certainly the ones leading to nucleotides. Therefore, the proposed model would have required a suite of true enzymes which could interconnect targeted reactions, so it faces all of the probabilistic hurdles mentioned above. The challenges of forming ribozymes are just as daunting for the same reasons.
I believe that Carter and Willis’ 2017 paper in Molecular biology and Evolution goes some of the way towards rendering the problems you allude to more tractable. A few quick quotes from the paper will illustrate my point:
Urzymes (Pham et al. 2007, 2010; Li et al. 2011, 2013) have ∼120–130 amino acids and retain all three translation functions of contemporary synthetases and accelerate amino acid activation by 109-fold, with significant specificity. Class I and II protozymes of ∼46 amino acids contain the ATP binding sites of the respective aaRS, bind ATP tightly, and accelerate amino acid activation 106-fold (Martinez et al. 2015)…
Superimposing Class I and II aaRS catalytic domains reveals small invariant cores, distinct from idiosyncratic elements unique to each amino acid. Like Russian Matryoshka dolls, parallel deconstruction of both Class I and II aaRS families reveals nested, increasingly conserved modular catalysts of nearly equal molecular mass (Carter 2014): catalytic domains (200–350 residues), urzymes (120–130 residues; Pham et al. 2007, 2010; Li et al. 2011, 2013), and protozymes (46 residues; Martinez et al. 2015), each retaining conserved portions from its preceding construct.
Urzymes retain all necessary functions of full-length aaRS, albeit with lower proficiency and specificity, and are analogous to using “molecule” to define the smallest unit of matter that retains all properties of a chemical substance. Protozymes, on the other hand, approach the smallest polypeptide catalysts, but have not yet been shown either to acylate tRNA or to discriminate significantly between different amino acids, hence are perhaps more analogous to “atoms.”…
Phylogenetic ancestries of contemporary Class I and II aaRS project convincingly back to a single gene. The simplicity of such a gene and the mapping of amino acid chemistry to tRNA identity elements furnish a conceptually consistent “boot block” (fig. 3) substantially reducing the challenge of understanding how genetic coding might have emerged from a peptide/RNA partnership.
What’s your opinion of the plausible model the authors sketch in section IV, part B of their paper,of the coevolution of Iinheritance and gene expression? Cheers.
I reiterate this question again. It is important.
I’d also add that we do not know how large our universe is. We know how large the observable universe is, and we know the laws of physics limits our view. So we do not really know how many habitable worlds are beyond our view. I’d think that a truly infinite universe is not likely, however, it might be orders of magnitude larger than we what we can observe. In fact, as Koonin has argued, the difficulty of abiogenesis can be used as a argument for the multiverse (or a larger universe than we can observe).
I just came across the following comment by a reader named Rumraket over at The Skeptical Zone. I gather he’s a biologist. What do you think of his argument?
There actually is evidence for abiogenesis (not unassailable proof, but evidence nonetheless) of the hypothesis that life originated from non-living materials by a process of physics and chemistry. The evidence is that the inferred amino acid frequencies in the phylogenetically inferred ancestors of the oldest known proteins, increasingly correlate with the distribution of amino acids produced in abiotic chemical reactions, and predicted to result from them by thermodynamics, as we go further back in time. As one would expect if life originated by a blind, unguided physical and chemical process whereby the first proteins were synthesized by polymerization of the sorts of amino acids that existed and therefore were the only ones available in the prebiotic environment.
Brooks DJ, Fresco JR, Lesk AM, Singh M. Evolution of amino acid frequencies in proteins over deep time: inferred order of introduction of amino acids into the genetic code. Mol Biol Evol. 2002 Oct;19(10):1645-55. [PMID: 12270892]
Higgs PG, Pudritz RE. A thermodynamic basis for prebiotic amino acid synthesis and the nature of the first genetic code. Astrobiology. 2009 Jun;9(5):483-90. [DOI: 10.1089/ast.2008.0280]
Trifonov EN. Consensus temporal order of amino acids and evolution of the triplet code. Gene. 2000 Dec 30;261(1):139-51. [PMID: 11164045]
This is evidence for a physical/chemical origin of life from non-life, and evidence against intelligent design, because this is the kind of evidence you would rationally predict if life originated by a chemical and physical process from non-life. But if life originated by intelligent design, the designer could have made the first life to exist with basically any distribution of amino acids that the designer wanted . For example, the designer could have made the first life to exist with the exact same distribution of amino acids that we see in life that exists today on Earth in 2018. Yet that is not what we see. As we go further and further back in time, the proportion of amino acids used in proteins increasingly mirrors the kind of distribution of amino acids detected meteorites, space, and various non-biological chemical reactions. This distribution is also predicted by thermodynamics to result from non-biological, unguided chemistry.
I don’t think the evidence Rumraket puts forward discredits Intelligent Design, as one could always opt for a front-loading scenario. However, it does seem to be strong prima facie evidence for abiogenesis. Thoughts?
Arguments that run “an intelligent designer would have…” are theological, not scientific, and all too common. On another view, it would be just as rational for the designer to use easily available materials as not: just as the fossil record might suggest the designer adapted existed organisms, rather than starting from scratch each time.
On the other hand, I’m not sure why naturalism gets a free pass on mechanism, simply by (provisionally) identifying raw materials. You still have to explain how Portland stone got to be Exeter Cathedral if you want to exclude design, rather than arguing that an architect would have invented some unknown material.
The argument was actually “an intelligent designer could have”, not “would have”. The point it raises is valid; a naturalistic explanation makes good sense of the available data, but an intelligent designer explanation begs a whole lot of questions and requires a pile of assumptions to support it.
What does “use easily available materials” mean, and why would the designer do this? For convenience? Is it because the designer would find it difficult to get materials any other way? We know why mortal, fallible intelligent designers use easily available materials. Did you have a mortal, fallible designer in mind? This is where the assumptions and question begging start to pile up.
Who is giving it a ‘free pass’? The research is attempting to identify materials and conditions available. At no point are researchers working on origin of life scenarios saying “Well, that’s the answer! Our work is done.”
The reason why ‘naturalism’ or natural mechanisms are being heavily investigated is because ‘intelligent design’ doesn’t have much traction, mechanistically or theoretically. First, it’s not clear there was an ‘intelligent designer’ or even an ET operating on Earth. Such entities seem to have left precious little orthogonal evidence of their existence over the eons through the history of the Earth. Second, exactly what sort of positive research has been proposed for the ‘intelligent origins of life’? What should one expect to see and what patterns of life should we expect? As it stands now, the overwhelming majority of work on “intelligent origin of life model(s)” involves negative arguments. While one cannot posit why an intelligent designer would clean up its tracks and/or otherwise leave no direct evidence of its existence over the millennia, I suppose it remains possible that one did seed Earth with life. But that just makes the work for “intelligent origin” proponents so much harder than that faced by those attempting the investigate the creation of life via natural mechanisms.
There might be any number of theological reasons for a designer, or God,working with what is already there. Take (just since I happen to be reading him) the creation theology of T E Fretheim, who tends towards an Open Theism, process theology, position in which God relates in a two-way fashion with what he has made, and the relationship is central to his creative nature.
The less process-minded theologian would, nevertheless, be able to look at the way that God, in the Bible, works in a developmental way through human history to conclude that God is a God who prefers to work through intelligible narrative. Abraham is called from an existing people, not poffed into existence. Likewise Israel. Likewise even Jesus, and likewise each person called to new life in him, though in all these there is an irreducible supernatural element. That is even so in the Genesis 1 account, when the seven day creation, however interpreted, unfolds in a rational rather than a “magical” way.
But that’s not the point in relation to Vincent’s source: to say that a designer _could _ have worked in some way that required no connection to the history of previously created entities and events, and that this is therefore more likely, is still a theological assumption that invites the response, “but you have no warrant to say that he did.”
And that is especially true when the sum total of ones appeal to entirely undesigned causes is the mere existence of materials, rather than any theory as to their transformation into life. Plus, of course, Vincent’s entirely valid point that the existence of certain amino acids from abiotic reactions is a result in itself of the very special constitution of the cosmos.
But this is the point, the fact that such a question results in mere hand waving and guesswork, proves that the original premise (that “God did it this way”), has nothing to support it than piled up assumptions.
That is one of the strongest possible arguments against ID.
I will write an ENV article in a few weeks addressing Adam and the Genome where I will discuss this issue in depth. I am afraid I will be too swamped to respond properly until then. In short, OOL demonstrates that a materialistic model for life is inadequate. Instead, information must be included as central. This fact has major scientific and theological implications. Here are some interesting comments from Paul Davies and Sarah Walker’s article “The Hard Problem of Life”:
If one insists on attributing the pathway from mundane chemistry to life as the outcome of fixed dynamical laws, then (our analysis suggests) those laws must be selected with extraordinary care and precision, which is tantamount to intelligent design: it states that “life” is “written into” the laws of physics ab initio [from their inception]. There is no evidence at all that the actual known laws of physics possess this almost miraculous property.
Here it seems clear that it is the information content of the genome — the sequence of bits — and not the chemical nature of DNA as such, which is (at least in part) “calling the shots”… On practical grounds alone, we need to remain open to the possibility that the causal efficacy of information may amount to more than a mere methodological convenience, and might represent a new causal category not captured in a microstate description of the system. What we term “the hard problem of life” is the identification of the actual physical mechanism that permits information to gain causal purchase over matter. This view is not accommodated in our current approaches to physics.