Reaping the Whirlwind: protein function without stable structure


(Raymond Isbell) #162

Really? Here’s a quote from the endorsement by Denis Noble that sounds promising. What is that you don’t like?

“Starting from his early encounter with the work and ideas of Barbara McClintock, through to his work on systems engineering as the key to understanding organisms, Jim Shapiro has new insights on all the central issues of evolutionary theory.”

Shapiro, James A… Evolution: A View from the 21st Century (FT Press Science) . Pearson Education. Kindle Edition.


(Raymond Isbell) #163

The word “extended” suggests they recognize that current neo-Darwinism is insufficient. Also, they are in search of a replacement for neo-Darwinism because of that fact. From what I’ve read/heard, they haven’t found it which is why they are searching. One of the primary reasons they see neo-Darwinism as insufficient is because of the Stochastic models that show the mechanism to be too unlikely to happen by chance which is a key component of the theory. How does BioLogos address the unlikeliness problem? I’ve think I read somewhere that Doug Axe’s model was rejected where he estimated the prevalence of functional sequences of proteins in functional sequence space to on the order of 1 in 10^77 (10 to the 77th power). Are there other models? What is wrong with Doug Axe’s model? I’m trying to find some on the internet. What I’ve read so far is mostly denial rather than an easily explained rebuttal. If anyone can steer me to a really clear case I would appreciate it.


(Christy Hemphill) #164

Yes, but people have blown that up to mean “evolution is a flawed theory” which is not at all what they are claiming. Like on their own website where they say:

"According to some bloggers, the EES is an ‘attack’ on evolutionary biology, a lobby for a ‘paradigm shift’ or a complaint that ‘something is seriously wrong’ with the field? Is that so?

Absolutely not. These portrayals are extremely misleading and this project disavows any such claims. The Darwin review (Laland et al., 2015) should make this quite clear:

“[Evolutionary biology is] a highly successful research program” [p1]

“Following the advent of the Modern Synthesis, the field of evolutionary biology has continued to evolve, allowing incorporation of new theoretical and empirical findings” [p2]

“Evolutionary biology has never been more vibrant, and it would be a distortion to characterize it as in a (Kuhnian) state of ‘crisis’ ” [p10]

“the EES requires no ‘revolution’ ” [p10]

There are some other researchers who do criticize the field of evolutionary biology using inflammatory language (e.g. Fodor & Piattelli-Palmarini, 2010). This is strongly discouraged within the project and seen to be unjustified. However, individual scientists have the right to think differently and to express their views in the manner they see fit without vilification.


(Christy Hemphill) #165

There is this discussion: Series reviewing Douglas Axe's Undeniable

And this one: https://discourse.peacefulscience.org/t/art-hunt-to-doug-axe-invitation-to-discuss/1660


(Raymond Isbell) #166

Thanks. It seems that every time I ask a question, I get a reading list that adds to my already overly long list. I think I’m going to take a day or two to get thru some of this. It is, however, very interesting. Thanks again for the direction. As Arnold said, “I’ll be back!”


#167

More like they recognize the current theory is incomplete. Evolution works through many different methods. It is much more than random mutation and natural selection.

No just an extension of the current theory.

Remember this is just one of the components and actually not the key component but just the first one identified.

The arguments for and against get pretty technical pretty quickly hence the links to resources that address them in depth. The link to peacefulscience would be your best starting point.


(Steve Schaffner) #168

When have you demonstrated that SE is useful as a framework for understanding cellular biology?

For starters, an endorsement by Denis Noble is a bad sign. More to the point, Shapiro is not the guy to read if you want to understand current evolutionary biology. He is at best a contrarian, and it’s usually a good idea to understand the consensus before reading attacks on it. He places a lot of emphasis on processes like endosymbiosis, genome duplication, and hybridization as central to evolution. These are sometimes indeed important, but the first two are extremely rare and the third is quite restricted in where it occurs. Meanwhile, he downplays the central process of natural selection, despite its prominence in theoretical, observational, and experimental evolution.

His big claim, that cells engage in “natural genetic engineering”, i.e. that they can steer their own evolution towards adaptive solutions, has convinced just about nobody within the field.


(Steve Schaffner) #169

More accurately, they recognize that neo-Darwinism, which has been defunct as a theory for decades, was insufficient but that it still provides a convenient punching bag for them to demonstrate the importance of their own grab bag of evolutionary processes.

Not really. EES is a collection of quite disparate ideas. Some of them are of great importance (evo-devo), some are highly speculative, and some are probably correct but of little evolutionary significance (trans-generational epigenetic inheritance). Most or all of them are already incorporated into current evolutionary theory, which has moved well beyond the neo-Darwinian synthesis.

I’ve read just about the entire suite of proposed EES ideas and I’ve never seen the slightest hint of this as a motivation.


(Raymond Isbell) #170

If SE is a useful framework for seeing how a system-of-systems is functionally integrated, and it can’t be applied yet to the cell because the cell is too complicated, and we don’t fully understand yet how it works, especially as an integrated whole, how can we be sure the cell demonstrates evolution? SE works and is great for organizing and framing complex systems so that they can be understood. If you can’t fit something into an SE framework, it suggests that our understanding of how the cell works hasn’t yet crossed the goal line. If we did understand the cell completely, SE would be an ideal way to present and document the cell’s functionality including all the specific proteins along with their mapping to their corresponding genes in the cell. All the C4 functions could also be integrated into the SE model to show clearly how they are instantiated, controlled, and support the detailed functions throughout the cell. Shapiro recognizes it.


(Raymond Isbell) #171

SE may also be a good tool that can help us verify that neo-Darwinism or EES is correct (or not).


(Steve Schaffner) #172

That’s your first premise, and it’s one whose general correctness you have simply assumed. SE is clearly a useful framework for seeing how human-engineered systems are functionally integrated. Is it a useful framework for understanding how biological systems operate? That’s the question I’m asking you to consider.


(Raymond Isbell) #173

That’s my engineering training and mindset sneaking in. Establishing organization helps to see structure that, in turn, leads to an ability to understand what you’re observing as well as verify that your understanding is correct. I’m sold on it as an approach to understanding complex systems.

I can’t imagine how it wouldn’t be. That’s one of the reasons I’m pitching it to you guys. I want to get your thoughts on it.

I think that’s the current sub-theme of this forum, i.e., can SE help us understand neo-Darwinian evolution as a viable model for cell life? I don’t think it can hurt, and who knows what a rigorous look at the cell from the viewpoint of a trained systems engineer might reveal? SE is solid as a scientific approach, so I suspect it will reveal much as it’s applied to the cell. I’ve actually started a workflow model of the mitochondria function using an SE methodology that I adapted from use in some of our intelligence production systems. One of the reasons I’m using it is because it helps identify and document dependencies and relationships.


(Steve Schaffner) #174

Your inability to imagine that it’s not a useful framework is precisely what I’m suggesting you work on. Try imagining why a framework invented to describe one class of systems might not be useful for a completely different class. So far, I recall you drawing two conclusions about biology based on your background in SE. One was that organisms would be brittle under changes to proteins, and the other was that there was an orchestra director controlling cellular processes. Both of those conclusions were incorrect. Those data points suggest that SE – at least as you are currently applying it – is not in fact a useful framework for biology.

I’ve seen plenty of people come into biology from other disciplines (including myself), including engineers, and they have brought many useful insights and techniques. But the successful ones have made a mental adjustment, realizing that biology is not physics, or electrical engineering, or whatever. It really helps to start with a little humility.


(Raymond Isbell) #175

This is an interesting observation. If there are two conclusions that I have offered, you have missed them both. I would suggest that the first conclusion, and by far the most important, is that SE, as a sound scientific discipline, offers to provide a structured and ordered look at EC. At the highest level, that look suggests that EC is a very weak hypothesis for explaining what we observe both in the fossil record and what’s current alive today. SE is a tool that “opens the hood” so to speak so that one can take a deep and critical look at some of the processes that are going on in living cells. Once understood, those processes can be assessed for their fitness as an explanation. Why anyone would push back on taking a closer and more critical look is beyond me (forgive my ignorance) unless they have something to hide. One would think that either side of this debate would welcome any strategy, method, or approach that could add insight into the workings of the cell. What is that insight? Simply that a more accurate and complete identification of each cellular process with its function(s), its relationships to other processes, and its sensitivity to the input parameters from those processes on which it depends will almost certainly add to a better understanding of the cell (system-of-systems). That in turn would help in deciding whether EC or Design is the best explanation both for the cell’s origin as well as its operations and sustainment.

Inclusion of robustness, flexibility and redundancy (RFR) are hallmarks of design as they reflect the highest levels of intellectual analysis of system processes and their functions. They add to the complexity already found in the cell. Fault Tolerant (FT) systems are much more complex than those without FT integrated into sub-system functions. They require more lines of code and more complex logic necessary to identify the particular fault and the best approach for mitigation. FT systems therefore require anticipation of failure modes, detailed knowledge of those failure modes, identification of other dependent sub-processes and their sensitivities to the failed system’s input parameters, and finally, design of work-around processes to mitigate the effects of each failure, i.e., design of the FT functionality necessary to keep the cell working when a failure mode has been realized. So you can see that RFR function is provided by FT. But FT increases the complexity of a cell’s design and the number of new specific pathways that must be in place in order to provide the RFR you insist is present in the cell. And we know that increased complexity translates into a lower probability of a cell evolving by chance and natural selection. Does it rule it out? No, but it speaks loudly regarding the feasibility of EC as a good explanation for observed cell function.

The second conclusion you see me bringing in is that there is C4 functionality actively controlling macro level cell function. I suspect that you don’t understand what I have in mind when I use that term. An example may help. Consider the navigation function that is clearly in play for nearly every protein in the cell. Each protein has a one or more functions to perform in the cell. How does that protein know where to go as soon as it’s generated? When does it go there? Are there alternative routes? Which route is the best? Is it to meet up with an enzyme to enhances its function? When does meeting occur? What if the enzyme is not ready? How long will it wait for the enzyme to also navigate to the rendezvous point? Are there protein machines that must also be at the navigation point to help transport it its next stop? Navigation function requires input of starting and ending points. It requires processing to perform the calculation of an initial heading (direction of travel), points where the heading must change, movement speed, etc. It must also have a performance feedback capability to ensure it stays on course and time. How is error detected, measured, new course data calculated, and communicated to the transport function taking the protein to its final destination? If it’s to be joined by other proteins at its destination what function is coordinating and monitoring the navigation solution of each of them and then assessing the status of the final join up? If one or more proteins are falling behind in the trek to the join up point, what C4 function is doing that calculation, sending corrections to the individual navigation functions for each protein to speed up, change direction, etc? This is what I mean by C4 function. C4 function monitors the presence and performance of every protein in the cell. It has a way of identifying each protein, where it’s located, where it needs to go, when it needs to be there, how it must get there (does it need transport assistance?) and what to do when it arrives. The C4 function is doing all the monitoring, processing, coordinating, what to do when something fails (FT), and it likely hosts the master clock. How is the C4 function hosted? Is there a computer protein(s) in the cell that receives all the inputs, does all the calculations, broadcasts the results with a sophisticated communications system so that each cell can receive its message and not confuse it with another’s in an environment where the signal to noise ratio is very low? Do the communication systems use match filtering to pull the signals out of the noise? Does the protein needing to navigate have a communications receiver and processor to decipher the incoming communications signals (chemical? RF?, other) and translate it into mechanical action?

As you can see there’s a lot of engineering function going on in the cell. SE is a process that identifies all of it so that it can be understood. When you described my two conclusions, “One was that organisms would be brittle under changes to proteins, and the other was that there was an orchestra director controlling cellular processes. Both of those conclusions were incorrect.” I scratched my head and ask, “What is he thinking?” Are you saying that all the C4 functionality I mentioned above is not happening?

As I assess what I’m hearing from you guys on why EC is correct, I’m first realizing that you’re leaving out a lot of engineering detail. In lieu of that detail, I’m see high level “hand waving” descriptions of cell function such as the RFR and the narrative of hippos to whales. Then, I get push back on SE saying that “SE… is not in fact a useful framework for biology.” What’s puzzling is that SE is a tool that can dig down deep in the detail to determine if EC makes sense. I’m still looking for some good argument for EC, but so far, I’m not seeing it. I found a nice website on evolution at https://evolution.berkeley.edu/evolibrary/home.php. I’ll read thru that and see if will help me understand it better.


(Christy Hemphill) #176

I’m not totally following. SE is a product of design correct? So if it does not work to describe cellular function, does that mean you conclude that the cell is obviously not engineered? It seems you are trying to make the opposite point, that if cellular processes can’t be made to “make sense” using engineering logic, then obviously it’s engineered. I don’t see how that follows.

There’s insights and there’s “a complete accounting.” It seems like you are interested in the latter. Formal logic (a branch of mathematics) applied to language may lead to some interesting insights in linguistics, but it fails miserably to give a complete accounting of what humans do with language. That’s why translation software has been far more successful using AI learning programs to make statistical predictions based on lots and lots of natural language input than it was trying to program language ability based on if/then and +/- rules of logic. It seems there to me is a parallel there. At some point, researchers need to describe what cells do, not simply impose a system on their functions that they believe is coherent and logical and should describe what cells do. It wouldn’t make sense for me as a linguist to say that a description of a language was hiding something just because it failed to describe the language purely in terms of the system of formal logic. It would make even less sense for me to rate the “fitness of the explanation” in terms of how much formal logic it employed. It would make no sense for me to assert that if I couldn’t explain a language in terms of formal logic, it was proof children couldn’t learn that language via natural processes and therefore we know God implanted the language in their brains.

It would make a lot more sense to ask if formal logic was the right tool for the job. It doesn’t seem like you have ever acknowledged that SE might not be the right tool for the job you are asking it to do.


(Mervin Bitikofer) #177

Sorry if my jumping in with this is a bit of a discontinuity - as I’ve only lightly followed all the discussion above and not contributed. But part of the reason for that is that I’m under the impression that Steve @glipsnort is showcasing some of the tried-and-true methods of current biological sciences, not defending EC. He may or may not be on board with EC as such - which isn’t (wasn’t?) the issue here. At least recently he’s just asking why you think an engineering approach can offer better insights than the approaches and understandings developed over time by the experts actually in the field. And so far, you’ve essentially declared that in some a-priori sense, it should work, despite the data so far that would seem to indicate it doesn’t. “EC” (or Evolutionary Creationism) views such as are defended by Biologos enthusiasts here isn’t some separate approach or system for doing biological science. It’s a theological approach that stands or falls in theological or scriptural domains (whilst using and not ignoring science as one of the valuable inputs to all that.) It seems to me like Steve has just been asking you to support your case for the science - and (unless I’ve misunderstood or missed major exchanges above) it would seem disingenuous to try to hold Steve to account for any “failings”/“successes” that EC as such may have.

Regarding your appraisal of flexibility and redundancy - it would also seem to me that biology still has human engineering beat hands-down. Because while it is true that smashing any one little component in a typical system of some kind (my computer here) will impair if not completely disable it - the same is not true for biological systems. Steve has been pointing out to you that mutations and changes are happening all the time - leaving enough of us all more-or-less functioning okay (and others not - but they don’t survive and reproduce if it is serious enough). If that isn’t a robustly surviving system (as a whole) I don’t know what is. It seems to me that no systems engineering (even with all their redundancies) come close to approaching such a self-sustaining self-reproducing “system”. So I think it would be the “systems engineering” folks who could learn a lot about robustness from biology rather than vice-versa. Their tools may be more successfully invading your domain than your tools theirs.

(Sorry if I misrepresent what you’ve been writing, Steve. Please correct as needed.)


#178

SE is a tool that is quite useful when it is applied to systems designed by humans. But remember when your only tool is a hammer the problems all look like nails. The fact that the hammer doesn’t work well on screws doesn’t mean there is a problem with the hammer or the screws.

I am assuming you haven’t done any reading in microbiology. But if you would do so I think you would be amazed at the detail that is known. It is rather difficult to compress that type of information into forum posts without triggering the “hand waving” response.

Hippos and whales share a common ancestor. Whales are not a descendent of hippos.

To me the best argument for EC is we are told that God created life but not how He created life. He left that up to us to figure out. And when you add God and evolution you get intelligent design. Just not the ID version.


(Raymond Isbell) #179

Watch this 5 min video to see what SE is. (https://www.youtube.com/watch?v=m3L9bEAha1I) The cell is a complex system-of-systems, and thus, SE would be the method of choice to document its components, their relationships, processes they perform, and resulting end functions. If we did a systems engineering review of a cell, the output products would be a suite of manuals that identifies every part, how that part is specified technically, how it’s produced, how it functions both alone and with other components, how it’s triggered for action, etc. Most importantly, the manuals would describe the integrated function and relationships of all the component parts so that if a designer had need to change (modify or improve) its function, he/she could go the manual to learn about it, and then initiate a new design with suitable modifications. Applied to the cell, an SE set of manuals would allow anyone working with the cell the ability to understand all of the cell’s inner workings so that a better cell could be created if needed, or a sick cell could be repaired. So why haven’t we documented the cell from an SE standpoint? (You phrased it as “So if it does not work to describe cellular function…” There’s too much in the cell that we don’t understand. But we do know that it obeys all the laws of physics, chemistry, etc. There’s no magic going on, although the C4 functions that are obviously at play in the cell seem like magic. It’s definitely not like language which results from thinking.

We either fully understand the cell or we don’t. Clearly, we don’t. Will we ever get there? Who knows? My purpose in bringing SE into the discussion of EC is that SE tells us that for any complex system their sub-systems work as a coordinated unit. The sub-systems work in synchrony. That means that the sub-systems work together, and many of them in causal chains. Each process in the work flow triggers the next step. If one step has mutated so that its trigger function is impaired and the function following it fails to recognize the trigger, the process will stop. How sensitive is the rest of the cell function to the process that has failed? SE would provide that answer if it were known. EC Cell biologists assure us that the process won’t stop because there is robustness, flexibility and redundancies (RFR) that will allow the trigger to be recognized even in a degraded state. That’s what is known in SE terms as Fault Tolerance (FT). In complex systems FT is hard to produce because of its nature that depends on anticipating failure modes. Anticipation is not an attribute of a physical system. It’s an abstraction generated by a mind. Physical parameters may be associated with anticipation, but their identify is a product of thinking, not meeting a threshold such as a voltage level. Now that I think about it, FT in the cell is a strong indicator of design and seems logically impossible to come from a sequence of random mutations of nucleotides.

Regarding your suggestion that SE is the wrong tool, I would disagree. The Cell is as physical system obeying physical laws. That’s what SE does best. The problem with the Cell is that we just don’t understand all of its functions. You can’t document something you don’t understand. But there is much in the cell we do understand, and from what I’m learning the neo-Darwinian model is very weak in explaining it. Specifically, because of the need for coordinated change (RFR notwithstanding) across many of the Cell’s sub-systems, the likelihood of evolution by random variation at the nucleotide level generating anything other than destructive change is very unlikely. It’s actually more difficult (more unlikely) from a statistical standpoint to see FT evolving into a cell’s function than if all the exact changes in the sub-systems were to change simultaneously with the original nucleotide change. SE asserts that all of them must change simultaneously, and those changes must be highly specific (very improbable) if the change is to achieve anything other than destruction.


(Dennis Venema) #180

One of the analogies that I develop at length in my section of Adam and the Genome is comparing how populations of organisms change over time to how languages change over time. It’s a very good analogy (note, not perfect, but very good). The analogy can give non-specialists insight into how biological systems work because they are intuitively familiar with how languages change over time, and the analogy is a good one for biological change over time.

Like biological systems, languages are not brittle - they can withstand quite a lot of variation and not cease to function. Consider the variation in how modern English is spoken around the world - North America, the UK, Australia, and so on. Or how variation creeps in, generation by generation, in one place.

What you’re proposing is, to a biologist, the equivalent of saying that someone from the UK won’t be able to communicate with someone from Australia. Or that kids won’t be able to communicate with their parents. We know from direct observation that this isn’t a problem, even if there are differences. The system as a whole is robust in spite of the variation within it.


(Steve Schaffner) #181

Yes, you’ve captured what I was saying. There’s also this, though: many of the ideas that @Raymond_Isbell is offering from SE have in fact been subjects of thriving research programs within biology for decades. Biologists did not need input from engineers to ask how proteins get to where they’re needed in the cell, for example. (See Wikipedia for a brief description.)