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 — https://luysii.wordpress.com/2009/12/20/how-many-proteins-can-be-made-using-the-entire-earth-mass-to-do-so/. 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 https://luysii.wordpress.com/2010/08/04/why-should-a-protein-have-just-one-shape-or-any-shape-for-that-matter/
After that — have a look at https://luysii.wordpress.com/2010/10/24/the-essential-strangeness-of-the-proteins-that-make-us-up/.
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)– https://luysii.wordpress.com/2010/08/08/a-chemical-gedanken-experiment/.
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”
Chemiotics II 
This post is mostly something I posted on the Skeptical Chymist 2 years ago. Along with the previous post “Why should a protein have just one shape (or any shape for that matter)” both will be referred to in the next one –“Gentlemen start your motors”, concerning the improbability of the chemistry underlying our existence and whether it is reasonable to believe that it arose by chance.
In the early days of quantum mechanics Einstein and Bohr threw thought experiments (gedanken experiments) at each other like teenagers tossing cherry bombs. None of the gedanken experiments were regarded as remotely possible back then, although thanks to Bell and Aspect, quantum nonlocality and entanglement now have a solid experimental basis. To read more about this you can’t do much better than “The Age of Entanglement” by Louisa Gilder.
Frankly, I doubt that most strings of amino acids have a dominant shape (e.g., biological meaning), and even if they did, they couldn’t find it quickly enough (theLevinthal paradox). For details see the previous post.
How would you prove me wrong? The same way you’d prove a pair of dice was loaded. Just make (using solid-phase protein synthesis a la Merrifield) a bunch of random strings of amino acids (each 41 amino acids long) and see how many have a dominant shape. Any sequence forming a crystal does have a dominant shape, if the sequence doesn’t crystallize, use NMR to look at it in solution. You can’t make all of them, because the earth doesn’t have enough mass to do so (see “https://luysii.wordpress.com/2009/12/20/how-many-proteins-can-be-made-using-the-entire-earth-mass-to-do-so/). That’s why this is a gedanken experiment — it can’t possibly be performed in toto.
Even so, the experiment is over (and I’m wrong) if even 1% of the proteins you make turn out to have a dominant shape.
However, choosing a random string of amino acids is far from trivial. Some amino acids appear more frequently than others depending on the protein. Proteins are definitely not a random collection of amino acids. Consider collagen. In its various forms (there are over 20, coded for by at least 30 distinct genes) collagen accounts for 25% of body protein. Statistically, each of the 20 amino acids should account for 5% of the protein, yet one amino acid (glycine) accounts for 30% and proline another 15%. Even knowing this, the statistical chances of producing 300 copies in a row of glycine–any amino acid–any amino acid by a random distribution of the glycines are less than zilch. But one type of bovine collagen protein has over 300 such copies in its 1042 amino acids.
One further example of the nonrandomness of proteins. If you were picking out a series of letters randomly hoping to form a word, you would not expect a series of 10 ‘a’s to show up. But we normally contain many such proteins, and for some reason too many copies of the repeated amino acid produce some of the neurological diseases I (ineffectually) battled as a physician. Normal people have 11 to 34 glutamines in a row in a huge (molecular mass 384 kiloDaltons — that’s over 3000 amino acids) protein known as huntingtin. In those unfortunate individuals withHuntington’s chorea, the number of repeats expands to over 40. One of Max Perutz’s last papers [Proc. Natl. Acad. Sci. USA 99, 5591–5595 (2002)] tried to figure out why this was so harmful.
On to the actual experiment. Suppose you had made 1,000,000 distinct random sequence proteins containing 41 amino acids and none of them had a dominant shape. This proves/disproves nothing. 10^6 is fewer than the possibilities inherent in a string of 5 amino acids, and you’ve only explored 10^6/(20^41) of the possibilities.
Would Karl Popper, philosopher of science, even allow the question of how commonly proteins have a dominant shape to be called scientific? Much of what I know about Popper comes from a fascinating book “Wittgenstein’s Poker” and it isn’t pleasant. Questions not resolvable by experiment fall outside Popper’s canon of questions scientific. The gedanken experiment described can resolve the question one way, but not the other. In this respect it’s like the halting problem in computer science (there is no general rule to tell if a program will terminate).
Would Ludwig Wittgenstein, uberphilosopher, think the question philosophical? Probably not. His major work “Tractatus Logico-Philosophicus” concludes with “What we cannot speak of we must pass over in silence”. While he’s the uberphilosopher he’s also the antiscientist. It’s exactly what we don’t know which leads to the juiciest speculation and most creative experiments in any field of science. That’s what I loved about organic chemistry years ago (and now). It is nearly always possible to design a molecule from scratch to test an idea. There was no reason to make [7]paracyclophane, other than to get up close and personal with the ring current.
If the probability or improbability of our existence, to which the gedanken experiment speaks, isn’t a philosophical question, what is?
Back then, this post produced the following excellent comment.
I’m not sure your assessment of what Popper would regard as science is accurate. Popper advocated “falsifiability”, i.e. that a statement cannot be proved true, only false. Non-scientific statements are those for which evidence that they are false cannot be found. You are in fact giving a perfect example of a situation where falsifiability is useful. If you tested, as you suggested, a million random proteins and many of them formed structures reliably, this would in fact disprove the hypothesis fairly conclusively (if only probabilistically). The fact that the test was passed by the first million proteins would be evidence that the theory was true (though obviously not concrete).
Also, it is relatively easy to choose what random proteins to make. Just use a random number generator (a pseudorandom generator would do too, probably). It doesn’t matter that they would be unlikely to produce a specific sequence generated in nature, as we are looking at specifically wanting to look at random sequences. The idea that 300 glycines is particularly unusual if protein generation is random is probably one which should be treated with a degree of caution. As the sequence was not specified as an unusual sequence beforehand, there are a large number of possible sequences that you could have seized on, and so care is needed.
This is only the most obvious experiment that could be carried out to test this idea, and I’m sure with advances, there is the distinct chance that more ingenious ways could be devised.
Additionally the the mass restriction is not in fact terribly useful except as an illustration that there is a massively large number of proteins, as once you have made and tested a protein, you can in fact reuse its atoms to make another protein.
Finally, I haven’t read Wittgenstein, but that final quote does not really support your statement that he is “anti-science” or would be against the production of novel cyclophanes. Organic chemistry clearly lies in the realm of “what we can speak”, as we are in fact speaking about it.
Posted by: MCliffe
My response —
MCliffe — thank you for your very thoughtful comments on the post. It’s great to know that someone out there is reading them.
Popper and the logical positivists solved many philosophical problems by declaring them meaningless (which Popper later took to mean not falsifiable). Things got to such a point in the 50s that Bertrand Russell was moved to came up with the meaningful (to most) but non-falsifiable statement — In the event of a nuclear war we shall all be dead.
You are quite right that it is easy to make a random sequence of amino acids using a computer. It’s been shown again and again that our intuitive notion of randomness is usually incorrect. I chose collagen because it is the most common protein in our body, and because it is highly nonrandom. Huntingtin was used because I dealt with its effects as a Neurologist (and because there are 8 more diseases with too many identical amino acids in a row — all of which for some unfathomable reason produce neurologic disease — they are called triplet diseases because it takes 3 nucleotides of DNA to code for a single amino acid).
Even accepting 300 glycines in 1000 or so amino acids (collagen) and putting that frequency into the random generator and turning it on, we would not expect those 300 glycines to appear at position n, position n+4, n+7, . . . , n + 898 randomly.
The idea of using the atoms over and over to escape the mass restriction is clever. Unfortunately it runs up against a time restriction. Let us suppose there is a super-industrious post-doc who can make a new protein every nanosecond (reusing the atoms). There are 60 * 60 * 24 * 365 = 31,536,000 ~ 10^7 seconds in a year and 10^10 years (more or less) since the big bang. This is 10^9 * 10^7 * 10 ^10 = 10^26 different proteins he could make since the dawn of time. But there are 20^41 = 2^41 * 10^41 proteins of length 41 amino acids. 2^41 = 2,199,023,255,552 = 10^12. So he has only tested 10^26 of 10^53 possible 41 amino acid proteins in all this time.
This is what I was getting at by saying the the gedanken experiment was not a priori falsifiable — we lack the time, space and mass to run it to completion. As you note, it could well end quite early if I’m wrong. Suppose 10^9/10^53 of the proteins DO have a dominant shape — the postdoc will be very unlikely to find any of them.
I think your final point is well taken. My reading of “Wittgenstein’s Poker” is that what he was saying in his last sentence really was “What we cannot speak (with certainty) of we must pass over in silence”. We cannot speak of the outcome of this Gedanken experiment with any degree of certainty.
Once again Thanks