Scientific hypotheses make empirical predictions

Faith & Science Conversation
76

As with all your other obfuscationist responses, you never seem to get to the heart of the matter.

Clearly. the procedures of science have established how the translation system operates. Knowing how the system operates is required to write textbooks and guide research, but is also required in the test provided.

But why is it that those procedures are sufficient for writing textbooks and guiding research, yet suddenly insufficient when it comes to the test. This is the equivocation you cannot hide.

Yet the answer is transparently obvious – there is no reason.

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[quote=“Biosemiosis.org, post:76, topic:4328”]
Clearly. the procedures of science have established how the translation system operates.[/quote]
Yes. Here’s an example:

Please note that the direct observations, provided in the tables, were simply measurements of radioactivity. This is what I mean by empirical predictions made by scientific hypotheses. They didn’t tell anyone else that they had to demonstrate or describe anything. Nuremberg and Mattaei won the Nobel Prize for this work.

Just to be clear, they repeatedly tested hypotheses of the form “repeats of the nucleotide X encode for polypeptides that are repeats of the amino acid residue Y.” This makes the empirical prediction that when radioactive amino acid Y is the only radioactive amino acid in the mixture of all 20, the cpm measured in the product will be much higher.

No, science is how we learn how the system operates. By making and testing empirical predictions, we don’t have to pretend to know.

[quote]But why is it that those procedures are sufficient for writing textbooks and guiding research, yet suddenly insufficient when it comes the test. This is the equivocation you cannot hide.
[/quote]You clearly are not engaging the most basic idea, which is that you bake in all your assumptions and interpretations before you gather new data. Therefore you aren’t following the procedures that real scientists use for guiding research.

In the Nobel-winning example I presented, the empirical prediction of a clearly stated mechanistic hypothesis was simply higher cpm in the product of the in vitro translation reaction.

This method is what helps to prevent us from engaging in wishful thinking and post hoc rationalizations.

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You clearly are not engaging the most basic idea, which is that you bake in all your assumptions and interpretations

Oh by all means, lay it out. Name them.

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If you think your hypothesis is correct, YOU will bake in all your assumptions and interpretations into your mechanistic hypothesis so that the only thing coming out in the prediction is the direct observation or measurement.

The example I provided shows that very clearly. See if you can find anything in it that resembles your, “Alternatively, if you cannot demonstrate that the requirements are false, then you concede…” or “You must demonstrate that the above system…”

80

And these baked-in assumptions are so clear that you can name them, right?

So name them.

Does the aaRS establish the amino acid-to-anticodon association? What is the assumption in that? Is the arrangement of the bases in a codon independent of the minimum total potential energy state of mRNA? What’s the assumption?

Are we now at assumptions that may not be named?

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Yes.

Here’s just one: “stop functions are necessary for proper translation.”

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So for you, the length of a polypeptide is independent of its function. Of course, eliminating the stop codon in any existing cell would cause immediate catastrophic failure of the system. However, that fact can be disregarded because in your view, it would be unwarranted to hold (even provisionally) that function would be adversely impacted if every protein was transcribed all the way to the end of the chain, or to some other random length. In other words, if a protein functions at 200 aa’s in length, there is no reason to believe that adding several thousand extra amino acids to it would cause a problem. And again, for you, the alternative assumption that adding these extra amino acids would have no impact is clearly the warranted view.

Moreover, this assumption changes everything.

Because the function of protein is assumed to be independent of its length, the system now does not operate in one of the ways it is presented to, and it can probably now be safely assumed that the other physical requirements of the system are unnecessary as well.

I believe you may be onto something Ben. The notion that cells need a method to terminate protein synthesis is completely unwarranted folly.

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[quote=“Biosemiosis.org, post:82, topic:4328”]
Of course, eliminating the stop codon in any existing cell would cause immediate catastrophic failure of the system.[/quote]
Absolutely, totally false.

No, your false claim can be disregarded because it is false and not a fact.

[quote] because in your view, it would be unwarranted to hold (even provisionally) that function would be adversely impacted if every protein was transcribed all the way to the end of the chain, or to some other random length.
[/quote]Provisionally? And why did you need to add “every” to “protein”? Your claim is that “stop functions are necessary for proper translation.”

Amber suppressor. Ochre suppressor. Opal suppressor. Look them up.

[quote=“Biosemiosis.org, post:82, topic:4328”]
The notion that cells need a method to terminate protein synthesis is completely unwarranted folly.
[/quote]Maybe you should look for facts before claiming to know them.

But, hey, you’ve finally offered a testable hypothesis (albeit falsely claimed as fact) with an empirical prediction: if cells die when translation termination is disrupted, that predicts that if we mutate a tRNA to recognize one of the stop codons, the mutation will be lethal.

Guess what? The observation has already been made (hundreds, maybe even thousands of independent times!), but it’s still science from your perspective because what matters is that the hypothesizer doesn’t know the data.

84

Absolutely, totally false.

Let me get this straight, you think if you took any existing cell and removed its stop function (i.e. its capacity to build functional proteins at a specified length) you’d argue that the cell would survive?

Wow. That is a head-shaker.

Provisionally? And why did you need to add “every” to “protein”? Your claim is that “stop functions are necessary for proper translation.”

Oh, I see now, you’re gaming the issue.

When I talk about … “the constraints of a reading-frame code (Crick) are necessary to proper translation, (example: initiation at a specific location, direction of reading, and stop functions are necessary for proper translation)” … I am talking about the various classes of things that are required for the system to actually function as a reading-frame code. A further example of this would be the establishment of three nucleotides as the length of a codon.

This is all necessary because codons have a spatial orientation, which must also be established in the reading hardware. In other words, the codon “GAT” (xxGATxx) will not be properly translated if it is read from the wrong direction (TAG), or frame-shifted (xGA), or the reading machinery does not read three nucleotides (GATx), etc.

All of these constraints, including control over the length of the transcript and its product, must be established in the operation of the system. This is what enables combinatorial expansion, and gives the system the capacity to encode an open-ended amount of information, making cell organization, heritable variation, and Darwinian evolution possible.

So when I say to you “remove the stop function” I am saying that all you are left with are the various promoters for transcription and start codons for translation – but there is nothing on the other end of the process to terminate it – because the stop function has been removed from the operation of the system.

But in your response, you want to kindly leave the cell system running properly as it does, and then point to specific instances of aberrations or disruptions (i.e. read-through mutations, stop suppressors, non-sense mutations, alternate stops, etc, etc) and then say “SEE – the stop function is not necessary!”

What a bunch of crap.

You either just don’t understand the fundamental issues, or you are being intentionally deceptive. If it is the latter, then you don’t need me around for that.

85

I may be dumb or something, but this conversation leaves me baffled. What are you guys talking about? Is there something new about translation that has overturned the facts listed by Biosemiotics? I dont understand what your point is, Ben. The fact that amber suppressor mutations allow cells to produce full length proteins supports, rather than contradicts Biosemiotics point about stop codons being essential. I am also confused about your points concerning direct observation. Are you using the specific experiments used to demonstrate the code as an example of how a hypothesis can be tested experimentally? If so, I dont think that was clear.

86

Hello Sy,

As you surely must know, amber, ochre, and opal suppressor tRNAs cause translation of a large fraction of wild-type proteins to extend beyond the stop codon, because many stop codons are no longer recognized. In genetically tractable systems like C. elegans, one can produce strains in which multiple tRNAs recognizing a specific codon such as UGG are amber suppressors, and it takes a lot of them to produce toxicity. More simply, the effects of these suppressors are in no way limited to the mutant allele being suppressed. Many proteins are more than full-length and in no way “proper,” falsifying Bio’s claim.

Ironically, since we know that proper termination of translation is not lethal, evolutionary biology has an obvious explanation for why translation termination is much more intelligent than translation initiation.

Yes. I am pointing out that the predictions are empirical, in terms of cpm, with no fuzziness.

87

No, I’m pointing out that YOU are gaming by using vague terms to begin, then moving the goalposts when challenged. That’s the antithesis of a scientific approach.

So am I, but I am focusing only the weakness of your claims about a single particular class! But you’re just talking and not offering any hypotheses that make empirical predictions.

And I am pointing out that such a sweeping and vague statement is poorly conceived because it is full of untenable assumptions. You’ll tactically convert it to a much more specific one if you are challenged.

Let’s do science and convert your rude claim into a testable scientific hypothesis.

If I manipulate E. coli K12 so that translation of 8% of protein-encoding genes occurs improperly–specifically, a bulky tryptophan residue is inserted instead of stopping, will the bacterium live or die?

Do you see how the prediction is clear and entirely empirical?

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Understood. I thought you were talking about the function of tRNA suppressors to bypass early termination caused by a nonsence mutation to a stop codon, but yes, such tRNAs can also produce readthrough past the normal stop in some cases. And some of those proteins will be viable and active, others not. So technically you are right. in that Biosemiotics statement is not universally true. But by that token one could say the same about the majority of biochemical mechanisms in cells, since for every rule in cell biology there seem to exist exceptions.

Thanks for your clear and direct answers. I can only speculate that perhaps if you had given such an answer to Biosemiotics, a lot of the energy and argument above might have been avoided. Then again, I realize that I am not aware of the full history of this discussion, so I am only speculating.

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[quote=“Sy_Garte, post:88, topic:4328”]
And some of those proteins will be viable and active, others not.[/quote]
Hello Sy,

I doubt that this is true on a gene-by-gene basis, though. I suspect that it’s true on a translation-by-translation basis, as in translation pooping out at different distances from the unrecognized stop codon. Either way, proper termination is not necessary, which provides evolution with far more ability to tinker and refine mechanisms for termination than it has for initiation. An intelligent designer would have no such constraints.

I don’t think it’s generally true, either, and there is more strong evidence against Bio’s claim.

But translation is a particularly ironic choice since has an internal control addressing this. What happens if we construct an analogous tRNA for the initiating AUG?

Thanks for your clear questions.

[quote]I can only speculate that perhaps if you had given such an answer to Biosemiotics, a lot of the energy and argument above might have been avoided.
[/quote]We can speculate, but IMO a huge problem is that Bio has far too much emotional investment in his hypothesis to subject it to anything resembling empirical testing. A less severe form of this problem even can be spotted in some NIH R01 applications, when the applicant proposes to “explore my hypothesis” instead of just testing it.

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Hmmm Looks like you looked me up. Its OK. Im retired. Which is why I was able to come back to Biologos and comment freely.

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Hello Sy,

I don’t see why that looks like I looked you up. I’m just relating my experiences on study sections.

92

See message.

93

Here’s another empirical test of your hypothesis: we will never observe a normal gene that requires failure of the stop function of translation for all or any part of its normal activity.

Thus, if we observe even one, your hypothesis is falsified. Do you agree?

94

No, I’m pointing out that YOU are gaming by using vague terms to begin

Vague terms? Here are the terms I’ve given:

1) the arrangement of bases in each codon results in alternate amino acids being presented for binding
2) the aaRS establishes the amino acid-to-anticodon association
3) the amino acid-to-anticodon association is spatially and temporally isolated from the pairing of codons to anticodons during translation.
4) the arrangement of the bases in each codon is independent of the minimum total potential energy state of mRNA.
5) the constraints of a reading-frame code (Crick) are necessary to proper translation
four examples:
5a) initiation at a specific location
5b) direction of reading
5c) stop function
5d) three bases in a codon

That constitutes 5 predicted observations, with four examples of constraints given of the 5th observation. You’ve attacked 1 of those 9 items, suggesting that it contains baked-in assumptions that falsify the claim of the test – i.e. that genetic translation is a semiotic system using spatially-oriented representations and a reading frame code.

You haven’t even begun to falsify that claim, what you have done is assumed that the cell’s capacity to control protein length isn’t necessary to function - whereas I do not make that assumption because it’s both unnecessary and contrary to the evidence. The processes that the cell uses to control protein length are an observable reality of the system, both in transcription and translation. My view is based on the removal of those processes. Your view allows the cell to continue with those processes intact, and then you point out isolated instances of specific transcripts that are themselves controlled in length. You have further demonstrated that this less-than-earnest view is the only view you are willing to entertain.

I am not obliged to overlook the processes that the cell uses to control protein length – and I have no intentions of doing so. I’m not obligated to ignore that improper length often ends in non-function and disease. But even if you demand that you are correct under your terms, it doesn’t falsify the test. At the very most, it would only show that the observation of a reading-frame code doesn’t turn on controlling protein length, and so, the stop function shouldn’t be included among the examples given. This is clearly evidenced by the fact that you can’t attack any of the other examples in item #5, nor any of the observations 1 though 4. I expect that you will continue to ignore those remaining predictions.

1 Like
95

your rude claim

You can talk to me about rude claims when you deal with the ridiculous hit piece you wrote as the OP. After you sift through the pedantic nonsense, you can recant your claim that my argument doesn’t make predictions that are empirically verifiable.