Reaping the Whirlwind: protein function without stable structure

… A common ancestor that didn’t need to produce vitamin C because its African environment had plenty of fruit. Odd how that works.
That is just the first definition: “of or based on a hypothesis.” The second captures the connotation that you’re giving it: “Imagined or suggested but not necessarily real or true.” (This is all just hypothetical.)

Basically, when you say that the paper’s “conclusions are hypothetical,” you are formally correct, since the conclusions are based on the hypothesis, but this tautology tells us nothing at all, and the same could be said of every scientific paper in every discipline. In fact, I was reading a paper the other day, “Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid,” by James D. Watson and Francis Crick. You may have heard of it. In any case, I suddenly realized that the paper’s conclusions are hypothetical, and that the basis for concluding the double-helix is nothing but hypothesis. Sorry for the sarcasm (not really), but that is how meaningless your statement is. When you say that the conclusions are hypothetical, if you’re communicating anything at all, you’re communicating your sense that the conclusions aren’t necessarily “real or true,” which just happens to be untrue. The conclusions, based on the original hypothesis, are true, even if provisionally so, pending new information. Sorry. It seems that science just cannot arrive at absolute truth, either, no matter how hard it tries.

You constantly insert the condition that unless we have all possible knowledge of a process, then we effectively know nothing of it. That’s just wrong. Pascal had some good advice: “We must know where to doubt, where to feel certain, where to submit. He who does not do so, understands not the force of reason. There are some who offend against these three rules, either by affirming everything as demonstrative, from want of knowing what demonstration is; or by doubting everything, from want of knowing where to submit; or by submitting in everything, from want of knowing where they must judge.”


I’m not sure what you mean by “anecdotes”. These are facts. They’re observations we’ve made about the natural world. What scientists do is propose explanations for why the facts are the way they are. Descent with modification is one such explanation, proposed long ago, and tested against every new line of evidence we’ve been able to accumulate in the last 150 years or so.

Isn’t it curious that an idea thought up during the Victorian era continues to make excellent sense of observations we’re making now, with the latest technology? We’ve of course learned a lot since Darwin, but the basic idea he presented remains the best explanation for the data that we know of.


The point that I’m trying to make is that unless you know all the details, you must resort to abductive reasoning to decide what you believe. The ID and YEC folks don’t have all the facts either. But given the facts we do have, what’s the simplest and best explanation for what we observe? I’m simply trying to navigate thru the data we have to see if indeed it supports NDE as the best explanation. As I have looked at the data you claim is evidence I find it weak. Neither you nor I have the engineering detail that I’ve outlined earlier which would inform a deeper understanding and help us make a better decision. Currently advocates of NDE seem confident to conclude they are correct despite their knowledge that important detail is missing. ID and YEC proponents also know they are missing important detail. Given that the detail that I’ve described in SE terms is not available and not likely to be available soon given our current technology, it seems to boil down to how we weigh the data we do have. On the NDE side, you have anecdotal information with some marginally justifiable extrapolations. I’m seeing lots of biological eisegesis. On the ID side, they use the stochastic models, concepts such as irreducible complexity, etc. to offer arguments, that if true, say that NDE is extremely unlikely. (I think the stochastic models they present grossly underestimate the unlikelihood of NDE. My knowledge and experience with complex systems suggests to me that the stochastic models are an even stronger argument than the ID folks believe. I base this on recognizing that a beneficial change to an organism sufficient to bring Natural Selection (NS) into play requires that many other very specific changes to the sub-systems that comprise the suite of functions that are part of new capability in the organism must appear simultaneously if the new capability is to be viable. Assuming that there are evolutionary pathways to get to the improved state is an assumption that cannot be backed up with any scientific rigor. Irreducible Complexity (IC) provides insight. If chance is what does the changing, then all the components that form the IC unit must be in the new configuration and continue to work together as an integrated unit or it will fail. Claiming it will not fail because of RFR is conjecture. If RFR is present it makes the stochastic models favor ID & YEC even more. That all the sub-systems change by chance to the new coordinated suite of functions configured correctly to give the organism new improve function is wildly improbable. Perhaps that’s why God claims in Rom 1:18ff we can understand that He made it. To conclude that in that passage God is implying that He made it using the NDE modality seems unlikely.

As I think about it and what has transpired in the forum for past couple of weeks, I find it intriguing that you have concluded NDE is the best explanation. I really want to understand your reasoning. So far it has eluded me. Most of you only have an academic knowledge of systems engineering if at all. Having worked with it up close and personal and seeing the many barriers that surface as one deals with highly complex systems that work as an integrated unit, you become painfully aware of how sensitive the sub-systems are in their relationship to each other and how intolerant they are to aberration’s in each other’s performance. Random changes in one that are not accompanied by very specific changes to all those that depend on it is a death knell to a complex system’s continued viability. When faced with these facts, you seem to brush them away, and embrace ideas that have not and cannot be supported by proven facts. Instead you seem comfortable with anecdotal evidence and extrapolation that seems correct (personal credulity) but can’t be proven.

What is about the anecdotal evidence that is so compelling and inclines you to extrapolate?

It seems like we’re talking in circles, so I’m not convinced that this reply will be useful, since it is the same point that I and others have made from the beginning of this conversation.

Your argument is based on your understanding of human engineering (and at that only a subset of human engineering, as has been noted).

Biological systems are not systems engineered by humans.

Your intuitions about how biological systems work are incorrect.

Several biologists on this thread have pointed this out to you, several times over.

Until you gain an understanding of how biological systems actually work, your intuitions will continue to mislead you.

We do not embrace ideas that are not supported by facts. We, like virtually all other scientists, accept that evolution is the current best explanatory framework that explains why the vast array of facts we have assembled about the natural world is the way it is. Since it is such a well-supported explanation, we are reluctant to jettison it - but we of course would do so, if a better explanatory framework could be found. That is exactly what biologists have been trying to do for 150 years.

Let’s take embryonic hindlimbs in whales as an example: do you have an alternative explanation for why they are there? Or does anyone who rejects decent with modification as an explanation? Why do whales start making hindlimbs only to slap a second developmental program on top that halts and reverses the process?


We have tried really hard to explain why those sentences are all false in the context of biology, and therefore why your repeated uncharitable characterizations of biologists are also false.

You have now elected to describe genomics as “anecdotal evidence”? Dennis listed just a small subset of the kind of evidence that is explained by common ancestry. He focused on genomic data but there are many other sets of evidence that make no sense to me outside of common ancestry. Can you explain why you call genomics “anecdotal”? I can tell you already that this word is used differently by the scientists I know.

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You don’t need to know all the details before a reasonable judgment can be made. The YEC folks have none of the facts on their side. They have to reject every science that ends in -ology to reach their conclusions. Those ID folks who accept evolutionary science actually differ from us EC folks very little, when you get down to it. They simply insist that evidence for God’s involvement should be empirically detectable, while we beg to differ. Then, there are those ID folks who reject evolution entirely. They fall between YEC and “Evolutionary ID,” having rejected only half of the sciences that end in -ology.

If God was the engineer, only he has the level of detail that you require. Shall we wait for him to reveal the blueprints before we make a choice?

Just as an aside, it’s always a tell-tale sign that you’re dealing with a partisan when they constantly refer to “neo-Darwinian” (or simply “Darwinian”) evolution, rather than simply saying “evolution.” If you specify that you’re arguing strictly against NDE, then you’re arguing with an outdated definition of evolution. Just call it “evolution” and be done with it. We all know what you’re talking about.

Define “important.” In any case, I don’t suffer from “paralysis by analysis.” There is more than enough evidence to satisfy me and 98% of all scientists (presumably that includes biologists) that evolution is the simplest and best explanation, and God was guiding it every step along the way. (The last bit is my faith talking. Your mileage may vary.)


Actually, my intuition comes from both my academic, lab, and work experience building complex systems. Any system that faithfully uses the laws of physics and atoms/molecules to perform a function, simple or complex, has the right to use the adjective “engineering.” It applies whether in a spaceborne radar interferometer or in a cell. Notice the Wikipedia definition of engineering: “Engineering is the application of knowledge in the form of science, mathematics, and empirical evidence, to the innovation, design, construction, operation and maintenance of structures, machines, materials, devices, systems, processes, and organizations.” It’s interesting that you say, “Biological systems are not systems engineered by humans.” That’s perilously close to begging the question. After all, isn’t that the question we are debating? If that’s one of your foundational tenants to argue against my assertation that engineering as a framework for understanding the cell and using that understanding to aid in identifying the best explanation for its origin, you have won the argument by assuming your solution is correct and mine incorrect to prove the same. The difference between a humanly engineered system and a biological one is that the former is completely understood down to the lowest level of detail by its designer. Its complexity and all the relationships between its components are perfectly understood so that if a change to one is made, the impact to all the others is also understood. This enables the highly specific and finely tuned changes necessary to all the others to be made. That will ensure the system achieves its designed function.

When you say the cell is different, how so? Does it not obey the laws of physics? Is there magic going on in the cell so that an engineering framework is not applicable? What we do know is that the cell is vastly more complex that any humanly engineered system so that we cannot understand all the lower level working details. We see some of them and understand them well, e.g., electron transport to support ATP synthesis. It’s perfectly understood in an engineering framework, and there’s no magic going on. As I struggle to understand why you offer the claim that the cell is different and therefore doesn’t qualify to be analyzed with engineering rigor, I feel like Wile E. Coyote after being spun around by the Road Runner.

What you offer in lieu of an engineering framework are adjectives like RFR (which are perfectly understood to any software engineer) to paint a broad enough picture that says evolution is happening, but no questions allowed. When challenged, you assert that the cell is different than a humanly engineered system. A statement like that seems to have only one goal, and that is to disarm the opponent rather than offer a carefully reasoned answer that acknowledges the remarkable engineering going on in the cell. The fact is that you don’t understand how the cell achieves RFR. But we know for sure that good engineering science is going on. That implies a very good designer. That can’t be denied by declaring the cell is different than a humanly engineered system. That brings up the point that I’ve been pushing since the beginning, “If you don’t understand a process, how can you claim with confidence that evolution is the mechanism of its origin?” What’s so interesting about it is that humans were created in such a way that we can recognized designed objects 100 out of 100 trials. We can get a perfect score. A car, a plane, a train, and space shuttle, a brick a tire, etc. Why is that design has to be excluded when we see a flagellum motor or the ATP Synthase Enzyme? The engineering precision involved in one of the these nanomachines is a thousand-fold more elegant and efficient than any humanly designed system. Ask James Tour ( And they are perfectly integrated into the cell to achieve a precise and critical function.

Here’s a basic concept of biology that says your paradigm is incorrect:

Emergent Properties
When units of biological material are put together, the properties of the new material are not always additive, or equal to the sum of the properties of the components. Instead, at each level, new properties and rules emerge that cannot be predicted by observations and full knowledge of the lower levels. Such properties are called emergent properties (Novikoff, 1945).

Life itself is an example of an emergent property. For instance, a single-celled bacterium is alive, but if you separate the macromolecules that combined to create the bacterium, these units are not alive. Based on our knowledge of macromolecules, we would not have been able to predict that they could combine to form a living organism, nor could we have predicted all of the characteristics of the resulting bacterium.

Thus, our understanding of physical and chemical properties in lower levels of organization helps us understand only some of the properties of living organisms, which prevents use of a reductionist approach. No matter how well we understand the physics and chemistry of living systems, we must recognize that living systems, and other high integrative levels, have new and unique properties that emerge through the combination of the lower-level units of matter (Novikoff, 1945). Likewise, our understanding of the new emergent properties at a higher level does not help us understand the properties of the lower levels, because each integrative level of organization has its own particular structure and emergent properties.


@Raymond_Isbell Dr Isbell, you might find this discussion about James Tour helpful; there are a couple of threads there, too.


I haven’t seen anyone make that claim. Have you?

Every claim in that sentence is false.

You have told us, repeatedly, that you want to understand why we (and essentially all biologists) accept evolution as an explanation. You have told us repeatedly that you just don’t understand. I wonder whether the sentence above, and many like it that you have written, point to one reason you are struggling to understand. That reason is: you don’t respect people who accept evolutionary explanations, so you can’t incorporate their explanations of their own beliefs and knowledge into your narrative. Your narrative, consistently, imputes ignorance and duplicity to evolutionary biologists and those who accept the theory. My hypothesis is that this is one thing that is hindering you. And by the way, ‘hindering’ is the right word, because you are far from understanding basic evolutionary biology and from understanding the arguments that your friends here are trying to get you to see.

I could be wrong, of course, and I know that neither you nor I can read minds. I just think you should know that the repetitive nature of this conversation, in which a few interesting questions are swamped by the same errors over and over again, kinda begs for an explanation. In short: I can never know whether you are actually trying to understand the positions we hold, but I do know that you are so very wrong about what you project onto us that you have failed to even superficially understand what it is we do and don’t agree on.


This is one of (several) problems with your thinking. Biologists do understand quite a bit about how cells are resilient to the changes you claim must be catastrophic. But until you’re willing to put the time in to learn about biological systems (specifically certain areas of cell biology, developmental biology and population genetics) it’s difficult to have a meaningful conversation.

Have you noticed that even ID proponents who reject common ancestry but have training in biology (Doug Axe comes to mind) don’t make the sorts of arguments that you are making?


You’ve said it numerous times, and it was stated directly (Jay Johnson (233- “Here’s a basic concept of biology that says your paradigm is incorrect:”) Maybe I’m inferring that if my paradigm is incorrect, it means that my suggestion that engineering rigor is a dog that won’t hunt and won’t qualify for application to the cell. My bad if I’m incorrectly inferring such.

You said in your first post (#14 28 days ago) in response to my claim,

Yet I know that it’s not false. In an integrated system (cell or other) when you have sub-systems dependent on each other and one changes without a commensurate change in the others,it will cause problems and most likely will be fatal to the larger system-of-systems function. You offer RFR as the reason my assertion is false. Yet, my claim is based on solid science. Then you and others claims that the cell is different so that my proven scientific assertion doesn’t apply. I’m not trying to slam you guys. I am just trying to understand your reasoning behind your claim.

For Jay, thanks for the link to James Tour’s paper. I’ll read it and then respond to your post. You guys are intelligent and accomplished. I will not ignore or deny what you say until I understand you. We’re not there yet, but we’re making progress, and I’m learning. I’m pushing back on you to help me get a deeper understanding of your thinking. I apologize if I hit back to hard every now and then. I, like you, mean well. As I’ve said, I’ll publicly recant my design views if I see in the end that you are correct. Apparently Dennis went thru this. I’m learning from him so maybe I’ll get there too. SE is good science. I just need to see how it works in the Cell.


Yes, that’s a mistake, inferentially. In addition, I have noted to you at least twice that engineering perspectives (and deeper functional analysis) are both ways to motivate questions. And I have mentioned my own interest in design. So, while pursuing mistaken characterizations of what I and others think, you are missing opportunities to talk about topics that are actually interesting.

Your claim is contradicted by facts of biology that have been cited to you repeatedly. It’s not “RFR” that refutes your claim. Cells are robust. Metabolism is robust. Gene expression and protein synthesis are robust. These are bedrock basic facts, and you won’t be able to converse productively about evolution as long as you fail to understand them. Your SE perspective is made to look impoverished and even fundamentally mistaken, which it’s not, when you advance it by daily beating a drum of basic error.

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Yeah, that’s the nub of the problem. If you “know” that a conclusion about cells is true because your model tells you it is, and it turns out that it’s actually false, then the problem is in your model, not in the cells. SE provides models of systems, and if some systems don’t follow the model – well, that’s the way it is with models.

One of the clearer demonstrations of how robust cells are: you can very often take genes from one species and stick them into quite a different species (human to mouse, for example) with no problem. This is completely routine biology – “transgenic mouse” yields 2.2 million Google hits.


Heh, yeah, the converse is true too; I think I mentioned elsewhere in the thread the travails of biologists making the first mouse knockouts. So many of them had no phenotype that one journal (MCB) created a section devoted to papers that reported on knockouts with no phenotype: “Mammalian Genetic Models With Minimal Or Complex Phenotypes.” The unwelcome message was that mouse genetics and physiology are so robust that you can delete an entire gene, one that had been shown unequivocally to be involved in a specific developmental process, and yield no discernible effect on the animal.


Interesting? I’ll be the judge of that! haha

I hope @Raymond_Isbell doesn’t take this as a rebuke. I credit him for at least wanting to understand. This is more of a general observation. Anyway, I’m always fascinated by the fact that people almost never take the opportunity to ask questions and learn from you guys – actual experts in the field. Instead, they’d rather argue than learn. Amazing.

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It’s also often the case that an enzyme can retain its function even when significantly “trimmed” of amino acids.

Heck, there are even examples of vertebrate genes functioning in place of their invertebrate orthologs (“equivalents” for the non-biologists) despite what, a few hundred million years of divergence?


Indeed, consider this excerpt from a paper published in 1996, about an enzyme that can still function after having its core scrambled (amino acid-wise). You might recognize this work.

The central structural feature of natural proteins is a tightly packed and highly ordered hydrophobic core. If some measure of exquisite, native-like core packing is necessary for enzymatic function, this would constitute a significant obstacle to the development of novel enzymes, either by design or by natural or experimental evolution. To test the minimum requirements for a core to provide sufficient structural integrity for enzymatic activity, we have produced mutants of the ribonuclease barnase in which 12 of the 13 core residues have together been randomly replaced by hydrophobic alternatives. Using a sensitive biological screen, we find that a strikingly high proportion of these mutants (23%) retain enzymatic activity in vivo.


Well played, sir. I did recognize it, indeed.