The Wave Model for Capping and Cell Motions

Reply

The use of the word "wave" to describe several different phenomena may be misleading. Might I suggest substituting the term "ripple" in the case of physical (ie surface distortion) waves?

Trying to imagine this process, I think of macroscopic examples.

1. The caterpillar track model - as in a tank or bulldozer. A lump of mud on a tank track will be carried forward along the upper surface, ("forward" being the direction of travel of the tank)- so both tank and mud move in the same direction, though at different velocities. This is true of all wheel-like rotation.
2. The "true" caterpillar ( let's call it "centipede") model, where a rythmic pulsation of legs causes a vertical hump to propagate along the animal's back. From memory, the hump moves forward, so the direction of movement of a free particle on the creature's back would depend on the precise timing and position of the particle in relation to the position and timing of the hump. (This might also be true of a tank track of the early World War 1 type, where the upper surface sloped significantly).

Hmm. Are macromechanical models relevant at all? A litre of water deforms as a Newtonian fluid: A drop of water is dominated by surface tension. How does a particle move on the surface of a moving drop of water? I would guess that it again depends critically on timing and position, with added complications of surface tension and charge distribution. It will certainly move, but is there any need of a single mechanism?

How rigid is the outer surface of a cell? Does it flow like a glacier? Does the whole cell pulsate? Do cells have a distinct "top and bottom?"

Damn. I love it when my whole worldview flips.

Lay on Mr. Hewitt.

The outer surface of the cell is more or less an oily fluid, its actually a liquid crystal with a viscosity like an oil, a few poise.

There are numerous possible oscillators in the cells (See Berridge, Rapp and Treherne (1979) Cellular Oscillators. I am sure there are more recent works available.) The potential for oscillation arises in part because of the feedback loops inherent in the allosteric control which is part of many biochemical pathways. Hence, it is very common. Some of these oscillations will simply be general pulsations, if the cell cytoplasm is effectively mixed this will always be the case, but others will lead to waves.
 
Power source for waves

4. What powers the waves?

Finally then, coming to your question 4 above. Cellular processes are generally powered by ATP hydrolysis. Another source of power is also important in this context, namely the concentration differences between the inside of the cell and the outside that are maintained by various membrane proteins. The best studied stories on that point are the origin of transmembrane electrical potentials and nerve impulses - which describes the origin of an important wave type in great detail - and the chemiosmotic hypothesis for oxidative phosphorylation which describes how a transmembrane concentration gradient is used as a sort of battery whose energy is used to synthesize ATP.
 
Science, questions and lies

So, for those readers who have labored through this extended thread, what do we have? The wave model is a theory, it is a fairly well evidenced theory and it coheres well with the rest of biology and science but it is also a theory that is rejected by the great majority of workers in the field.

1. The question is why - what is the basis for rejecting this concept?
I don't know. I am unable to find any platform, any period of time or any mode of address that will elicit a meaningful, scientific reply to such questions.
During the course of asking these questions I have been given to understand, at the highest levels of science, that completely ignoring an alternative theory is considered acceptable. Popper's logic, I am told, is not how things work in practice.

It is perfectly clear that some of the most senior figures in British science regard lies and empty propaganda as just the way things are – you really should not expect anything else.

Why cling on to the cytoskeletal model – a model that is not well-evidenced, does not cohere well with the rest of science and is not well enough defined to make testable predictions?

The answer, I suggest is very simple. The reason for doing this is power.

We, the scientific establishment that is, ignore the alternative because we have the power to do so. We ignore the wave model because we cannot take credit for it. We are in charge of science, at least of this field, and we will destroy or suppress any part of it that we cannot take credit for.

That, in reality, is how science is and that is how science works.

What is presented as verified, validated, quality controlled fact that has emerged from a disinterested pursuit of truth is, at bottom, an expression of selfish vested interests - as often a manifestation of deceit as a statement of truth.
 
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So, for those readers who have labored through this extended thread, what do we have? The wave model is a theory, it is a fairly well evidenced theory and it coheres well with the rest of biology and science but it is also a theory that is rejected by the great majority of workers in the field.

1. The question is why - what is the basis for rejecting this concept?
I don't know. I am unable to find any platform, any period of time or any mode of address that will elicit a meaningful, scientific reply to such questions.
During the course of asking these questions I have been given to understand, at the highest levels of science, that completely ignoring an alternative theory is considered acceptable. Popper's logic, I am told, is not how things work in practice.

It is perfectly clear that some of the most senior figures in British science regard lies and empty propaganda as just the way things are – you really should not expect anything else.

Why cling on to the cytoskeletal model – a model that is not well-evidenced, does not cohere well with the rest of science and is not well enough defined to make testable predictions?

The answer, I suggest is very simple. The reason for doing this is power.

We, the scientific establishment that is, ignore the alternative because we have the power to do so. We ignore the wave model because we cannot take credit for it. We are in charge of science, at least of this field, and we will destroy or suppress any part of it that we cannot take credit for.

That, in reality, is how science is and that is how science works.

What is presented as verified, validated, quality controlled fact that has emerged from a disinterested pursuit of truth is, at bottom, an expression of selfish vested interests - as often a manifestation of deceit as a statement of truth.

But John, all you have done is outline a theory. It is fine as a hypothesis, as is the alternative baked bean cell movement theiory I have just invented.

If you want to convince me, do some experiments to show us cells moving using the waves you describe.

While you are doing this, please may I present an alternative hypothesis that has had some nice experiments done to support it:

Cellular Motility Driven by Assembly and Disassembly of Actin Filaments

What, specifically, do you disagree with in this article? It seems to me it gives a coherent picture of how the cytoskeletal model can drive cell movement.
 
Do you have any evidence for this model? Your website says :

In addition, I knew about Durham's ideas on cell waves, some data on cell oscillations and had attended talks on the Belousov-Zhabotinsky reaction - the extraordinary chemical reaction able to oscillate or produce wave patterns. The kinetic arguments used to explain that reaction, made it seem very likely that biochemical pathways would commonly produce similar behaviour. I had already published two theoretical papers on membranes, which I felt were my best published work, and wanted to develop that area so, in 1978, my experiments not working as desired, I set myself the theoretical task of devising a better explanation of capping.
I showed this preprint to the laboratories in Cambridge but was rather taken aback by the response. To a man, they acted as if nothing had been said to them. One person told me "I don't feel the field needs a new model at the moment", another thanked me for showing him this "interesting" paper, informing me he had nothing else to say.

This seems to suggest that your work was purely theoretical, and while it may have been an "interesting paper", do you actually have any reason why it should be taken any more seriously than just that?

I would also suggest that your attitude does not seem to be generally friendly and could be likely to put people off your advances just for that reason.
Scientists need more than just alternatives to suggest, they also need credit for their innovations. I had already seen how easily such recognition becomes detached from the real innovator and is appropriated by some scientific prince. Accordingly, my intentions and ideas were not discussed with workers outside my immediate laboratory until I had them in a draft manuscript form.
Refusing to discuss your work with your peers is generally not the best way to get anywhere in any proffesion. It appears that you had issues with the scientific community before your theory was even thought up. While personality conflicts should not affect science, the fact is that they do, and if you appear to be desperately trying to get credit, rather than doing science for the sake of science, you are unlikely to be as highly regarded as someone who works for the science and not just for themselves.
 
Inappropriate attribution of personality traits

Do you have any evidence for this model? Your website says :




This seems to suggest that your work was purely theoretical, and while it may have been an "interesting paper", do you actually have any reason why it should be taken any more seriously than just that?

I would also suggest that your attitude does not seem to be generally friendly and could be likely to put people off your advances just for that reason.

Refusing to discuss your work with your peers is generally not the best way to get anywhere in any proffesion. It appears that you had issues with the scientific community before your theory was even thought up. While personality conflicts should not affect science, the fact is that they do, and if you appear to be desperately trying to get credit, rather than doing science for the sake of science, you are unlikely to be as highly regarded as someone who works for the science and not just for themselves.

Dear Cuddles,

There is an ongoing tradition in biology to use the word "theoretical" in a very sneering tone. The evidence suportive of the wave model was reviewed in ch7 of "A Habit of Lies." You might want to look at that evidence.

I did not feel I was being unfriendly, uncommunicative or unprofessional in inviting colleagues to comment upon my ongoing work. I do not know why you look at those facts and then attribute to me a refusal to communicate. I have no idea why you think they were being friendly in declining to reply. It seems to me that you are inverting the facts and making an innapropriate attribution of traits to me. It is not the only one you make.

In one respect you are right, although I always wanted to do science, there were large parts of it I felt I could do without. When I returned to Cambirdge I already took the view that much of what was published as science was of no real value and that the scientific community were very corrupt. If you actually believe that science is honest, I suggest you join the SCIFRAUD list and glance through some of its archives, or look through some of the cases examined by the ORI and its predecessor the OSI. Even now, there are forms of scientific cheating that the ORI do not look into and, so far as I know, Britain has no professional body at all that investigates cases of scientific fraud.

In any event, then and now, I do believe that all investigators, at any level of seniority, should be able to discuss their work secure from the likelihood that their work will be plagiarized. You are free think otherwise if you wish but I am free to disagree with you - I do find it reasonable to expect that work done by me will be attributed to me. I do not accept that this expectation is an unreasonable impost upon professional colleagues.

In any event, I wrote my ideas up and then invited comment from several places simultaneously after I had placed my name on it. I do not agree that this is an abnormal way of proceeding.
 
But John, all you have done is outline a theory. It is fine as a hypothesis, as is the alternative baked bean cell movement theiory I have just invented.

If you want to convince me, do some experiments to show us cells moving using the waves you describe.

While you are doing this, please may I present an alternative hypothesis that has had some nice experiments done to support it:

Cellular Motility Driven by Assembly and Disassembly of Actin Filaments

What, specifically, do you disagree with in this article? It seems to me it gives a coherent picture of how the cytoskeletal model can drive cell movement.

I shall need to reply to this in a cuople of postings. I will return.
 
I shall need to reply to this in a cuople of postings. I will return.

Hi John, I do not mean to bombard you with articles, but I was intrigued by what you have posted so far. I have looked at some of the references you cited concerning movement of particles on cell membranes.

This paper Reactivation of cell surface transport in Reticulomyxa is a quite recent one that put latex microspheres on amoeba and watched them move. I would direct you to this quote in the abstract "organelles and surface-attached polystyrene microspheres remained firmly attached to the microtubule cytoskeletons". The same group has a more recent paper describing how plasma membrane domains are moved by the underlying cytoskeleton.

I am therefore at a loss as to why there should be some "extra" wave motion underlying cellular motion. Why is cellular motion not therefore driven by movement of the cytoskeleton and interaction with cellular adhesion molecules?
 
In these cases, particle movement is known to be wave driven, albeit that the cells of that tissue is ciliated.

I need to give Richard's citations some attention, but in the meantime, the statement quoted above has been niggling me. You cite the motility of cilia in your web pages as well, but I don't see how it is relevant. Indeed, in discussing the motility of non-ciliated cells I don't see how it is helpful to remind us of cilia. We have evidence for cilia moving in waves, I still don't see any evidence for waves existing in the situations that are relevant to non-ciliated cellular motility. I have re-read your Chapter 7 several times and find that it is like trying to grasp fog. I look for bits of evidence that build a case for your wave model and I find analogies and extraneous information. The whole of section 7.5 concerning calcium contributes nothing at all to the evidene for waves creating motility. Nowhere is any suggestion made as to how waves move cells.

Maybe I'm being thick, but as the possessor of more than one Cambridge degree I'd hoped I would not turn out to be too stupid to understand this.
 
I need to give Richard's citations some attention, but in the meantime, the statement quoted above has been niggling me. You cite the motility of cilia in your web pages as well, but I don't see how it is relevant. Indeed, in discussing the motility of non-ciliated cells I don't see how it is helpful to remind us of cilia. We have evidence for cilia moving in waves, I still don't see any evidence for waves existing in the situations that are relevant to non-ciliated cellular motility. I have re-read your Chapter 7 several times and find that it is like trying to grasp fog. I look for bits of evidence that build a case for your wave model and I find analogies and extraneous information. The whole of section 7.5 concerning calcium contributes nothing at all to the evidene for waves creating motility. Nowhere is any suggestion made as to how waves move cells.

Maybe I'm being thick, but as the possessor of more than one Cambridge degree I'd hoped I would not turn out to be too stupid to understand this.

You are not being asked to grasp fog, only to be rational. I see nothing wrong with reminding you of the waves on ciliated cells - unciliated cells in the human body are genetically identical with ciliated cells. Do you really believe that this genotype has produced two, totally different phenotypes?

If you take the example of the cilia in the lining of the lung, these waves have the function of moving particles, they are associated with calcium waves, calcium waves exist on all or virtually all eukaryotic cells, calcium concentrations are pivotal in controlling the contractile state of muscle, amoeboid cells, in muscle those proteins generate force by their contractile state.

If you read articles such as the Pollard paper, cited by Dr. Richard, these muscle proteins are not contractile at all - insted, in amoeboid cells muscle proteins generate force by assembling at the front and disassembling at the back. From evolutionary and protein chemical viewpoints, that claims seems abusrd and my point is that such beliefs are sustained simply by ignoring an alternative interpretations of the facts. However, I shall come back to Dr. Richard's posting.
 
Do you really believe that this genotype has produced two, totally different phenotypes?

That's another thing. I don't see that this 'evolvability' argument goes anywhere. Do I believe that one genotype can produce "totally different phenotypes"? Yes, of course. An epidermal keratinocyte and a retinal cone are pretty different phenotypes from one genotype. So, yes, if you could show that the processes in ciliated cells and motile non-ciliated cells were closely related you might comment on the parsimony of using a common underlying mechanism to solve two problems, but you can't argue this must be so.

If you take the example of the cilia in the lining of the lung, these waves have the function of moving particles, they are associated with calcium waves, calcium waves exist on all or virtually all eukaryotic cells, calcium concentrations are pivotal in controlling the contractile state of muscle, amoeboid cells, in muscle those proteins generate force by their contractile state.

If you read articles such as the Pollard paper, cited by Dr. Richard, these muscle proteins are not contractile at all - insted, in amoeboid cells muscle proteins generate force by assembling at the front and disassembling at the back.

Again, I'm not sure where this argument leads.

On the one hand you are invoking calcium's role muscle-type contractile mechanisms, but that does not show that the cytoskeleton is not involved in cell motility. It may show part of the mechanism of the cytoskeleton's role in contractility, but it does not distinguish your model from the cytoskeletal model.

But then, you seem not to like the idea that motility may arise from actin cytoskeletal assembly rather than its contractility. For one thing, these are not mutually exclusive. For another thing, any such refinement and elaboration of the cytoskeleton's mechanisms in motility doesn't refute the cytoskeletal model. If anything a deepening of the quality of the model lends the cytoskeletal model support. It does not seem to have much bearing on the 'wave model'. Again we have the problem of what does the 'wave model' consist. If you invoke all the mechanics of the cytoskeleton to drive your waves then your idea is just one aspect of that cytoskeletal model. If you are not invoking the mechanics of the cytoskeleton in driving your waves then I am not sure what you are arguing, not least because you do seem to have invoked it in your model.

It might help if you could lay out what are the features of the 'wave model' that distinguish it from the cytoskeletal model, and especially what makes it a model in its own right rather than being, at most, element of the cytoskeletal model.
 
Reply to Dr. Richard part 1

But John, all you have done is outline a theory. It is fine as a hypothesis, as is the alternative baked bean cell movement theiory I have just invented.

If you want to convince me, do some experiments to show us cells moving using the waves you describe.

While you are doing this, please may I present an alternative hypothesis that has had some nice experiments done to support it:

Cellular Motility Driven by Assembly and Disassembly of Actin Filaments

What, specifically, do you disagree with in this article? It seems to me it gives a coherent picture of how the cytoskeletal model can drive cell movement.



Thank you for this posting and for the reference. I don't think it the best exemplification of the problems with this field but I will use it as an example.

There are a number of general issues here and I will have to deal with them in turn. They are
1. Scientific logic.
2. Observational evidence and the degree of certainty that can be ascribed to it and the kinds of observational data that can or cannot be seriously disputed.
3. Theory – here I do not mean your ideas, I mean secure theory, evolutionary theory and thermodynamics and their implications for the kind of thinking displayed in the Pollard and Borisy paper.
4. Information and data theory, which is more or less a branch of thermodynamics (though less secure) and its implications for organisms and cells.

Beginning with scientific logic.
Popper, as you recall, has it that one cannot confirm theories, one can only disconfirm them, falsify them. Science, in short, is an essentially negative logic and a negative way of thinking. One cannot prove one's ideas, one can only give reasons for rejecting reasonable alternative theories. As a scientist, I presume you know this already.

Many people just ignore this kind of thing and I do realize that, in practice, it is not always easy to apply Popper's logic. Nonetheless his approach is widely seen as the best and ultimate logic of science. You and other workers in this field may believe that some other mode of thought is appropriate. If that is your opinion, it would be helpful if you would say so.

Popper's logic imposes certain core expectations on scientific debate of which two are relevant here. The first is that a theory should be articulated with sufficient precision that it can make testable predictions. In other words, a hypothesis is not worthwhile unless it is at risk of being refuted. You may not construct a hypothesis that is so general or unclear that it is immune from contradiction and apparent contradictions should be addressed. Second, alternative theories should be acknowledged and the reasons for rejecting them given. My aim is to know the reasoning that leads to the rejection of the wave model.

I come now to the Pollard and Borisy paper. You seem to feel that this paper is relevant yet it does not mention or discuss the wave model at all and does not seem to imply any reasoning process that might make predictions that could contrast it with the wave model. I would like to know of behaviours, found in living cells, that are explicable or predictable from this kind of cytoskeletal model and but which are uninterpretable in terms of analogous wave models.

The Pollard and Borisy paper describes an elaborated form of the cytoskeletal model for cell structure and function. Its substantial content is mostly just pen and ink drawings and the evidential status of the various features found in those drawings is unclear. I cannot discern any falsifiable predictions this model makes about the behaviour of actual cells. The criticisms Bretscher used to level and such ideas were always valid – which is not to say that his own lipid flow ideas were any better.

For the benefit of people who are not too familiar with cells, I would like to give a picturesque summary of the ideas underlying Pollard and Borisy's version of the cytoskeletal model. Imagine that the cell is a tent. The cell's outer membrane is a cloth and the cytoskeleton is an internal framework across which the tentcloth is stretched. This paper asserts that the cell moves by disassembling this internal framework at the back of the cell, transporting the disassembled components to the front of the cell, and then reassembling those components. It is, I think certainly true that such a mechanism would move a cell but I do not know of any species that moves by any similar type of mechanism. I therefore find this kind of suggestion fanciful. (Other versions of the cytoskeletal model have the cytoskeletal filaments behaving rather like railway lines with engines running along them and carrying cargo. This is equally improbable and parts of it are also implied by Pollard and Borisy's paper.)

But what, exactly, does Pollard and Borisy's description predict? It does not seem to predict whether cells have waves or whether external particles will move backwards, forwards, round in circles or not at all. So it has nothing to do with the wave model. It does not seem to predict whether external particles will adhere to the cytoskeleton. It offers no clue about why cells move or how they decide the direction of their motion. I don't see how it leads to any reasoning process able to produce testable predictions and, hence, I don't see it as a hypothesis. In what ways does this work articulate a theory of cellular action at all?

As indicated above, I will shortly return to this topic but I invite Dr. Richard to look at the tent analogy above. I ask him to add to it, modify it, suggest an alternative, simple description that gets at the nub of mechanism he seems to believe in. I ask him to describe that mechanism, in the simplest possible terms, and to indicate the reasoning process whereby it can lead to testable predictions. I also ask that he address the wave model, which is what this thread is intended to be about. If he rejects that model, would he please explain the basis for that rejection?
 
John,

You are absorbed by your model allegedly being ignored by others, but the purpose of a model is to enable to make predictions about the behaviour of a system. Buut unless your model says something distinctive and useful why should it not be ignored? What predictions for experimental data does your model make that would distinguish it from the cytoskeletal model?

To return to Popper, I can't see anything falsifiable in your model as you have framed it. That is not to say it is wrong, but unless it makes some predictions how can you test it?

I'm not sure anyone here is rejecting your model, as such, but we are struggling to find any need to invoke it. Detours into evolvability, ciliated cells, the calcium-dependence of motility do not demand that it is invoked.

Maybe I've missed you doing so, but it all boils down to you needing to make some predictions using your model.
 
Dear Cuddles,

There is an ongoing tradition in biology to use the word "theoretical" in a very sneering tone. The evidence suportive of the wave model was reviewed in ch7 of "A Habit of Lies." You might want to look at that evidence.

I have read it once again and I still have not seen any evidence. The only thing that comes close is a paper which did not come to any conclusion about the wave model, although you come your own conclusion about it. One paper who's conclusions contradict your own doe not seem to make a great case.

In addition, no sneering tone is intended when using the word "theoretical", it is simply an observation. It appears, from everything you have written, that you have come up with a theoretical model with very little evidence in support. Of course models are useful, and needed, but without a evidence in support they are worthless, and you have not provided much at all. If the evidence presented in chapter 7 is all you have, then I do not see why anyone should take it more seriously than other models with much more support.

I did not feel I was being unfriendly, uncommunicative or unprofessional in inviting colleagues to comment upon my ongoing work. I do not know why you look at those facts and then attribute to me a refusal to communicate. I have no idea why you think they were being friendly in declining to reply. It seems to me that you are inverting the facts and making an innapropriate attribution of traits to me. It is not the only one you make.

It seems you misunderstood me, I was actually saying the exact opposite. From the piece I quoted it appears that you did not discuss your ideas with anyone outside your own office, which is what I would consider uncommnicative. In addition, your reasons for doing so are stated as wanting to claim credit for work which you had not yet done. I definately consider this attitude unfriendly, and would not want to spend much time looking at such a person's work if there was other equally good work around.

In one respect you are right, although I always wanted to do science, there were large parts of it I felt I could do without. When I returned to Cambirdge I already took the view that much of what was published as science was of no real value and that the scientific community were very corrupt. If you actually believe that science is honest, I suggest you join the SCIFRAUD list and glance through some of its archives, or look through some of the cases examined by the ORI and its predecessor the OSI. Even now, there are forms of scientific cheating that the ORI do not look into and, so far as I know, Britain has no professional body at all that investigates cases of scientific fraud.

This comment only backs up my opinion. You cannot expect to be a part of a community if you openly say that "much of what was published as science was of no real value and that the scientific community were very corrupt". It would be nice if science could be conducted away from personalities, but the fact is that if you wish to be a respected scientist, labeling most of the community as useless frauds is not the best way to go about it.

I would add that I am involved with the scientific community, albiet a different field, and I have seen no evidence of fraud or corruption. Obviously these things happen from time to time, as with any large group of people, but I suggest it is nowhere near as common as you think.

In any event, then and now, I do believe that all investigators, at any level of seniority, should be able to discuss their work secure from the likelihood that their work will be plagiarized. You are free think otherwise if you wish but I am free to disagree with you - I do find it reasonable to expect that work done by me will be attributed to me. I do not accept that this expectation is an unreasonable impost upon professional colleagues.

In any event, I wrote my ideas up and then invited comment from several places simultaneously after I had placed my name on it. I do not agree that this is an abnormal way of proceeding.

Of course you should be free to have credit for your work, but it seems that your desperation to ensure you had this, apparently without any particular reason to think you would not be afforded such, appears to be the reason why you were not accepted as part of the community that you wanted credit from. I would also say this does seem a fairly unsual way to procede, since usually ideas are thoroughly discussed among many people long before they begin to be written up, although you are by no means unique in proceding that way.
 
Thank you for this posting and for the reference. I don't think it the best exemplification of the problems with this field but I will use it as an example.

There are a number of general issues here and I will have to deal with them in turn. They are
1. Scientific logic.
2. Observational evidence and the degree of certainty that can be ascribed to it and the kinds of observational data that can or cannot be seriously disputed.
3. Theory – here I do not mean your ideas, I mean secure theory, evolutionary theory and thermodynamics and their implications for the kind of thinking displayed in the Pollard and Borisy paper.
4. Information and data theory, which is more or less a branch of thermodynamics (though less secure) and its implications for organisms and cells.

Beginning with scientific logic.
Popper, as you recall, has it that one cannot confirm theories, one can only disconfirm them, falsify them. Science, in short, is an essentially negative logic and a negative way of thinking. One cannot prove one's ideas, one can only give reasons for rejecting reasonable alternative theories. As a scientist, I presume you know this already.

Many people just ignore this kind of thing and I do realize that, in practice, it is not always easy to apply Popper's logic. Nonetheless his approach is widely seen as the best and ultimate logic of science. You and other workers in this field may believe that some other mode of thought is appropriate. If that is your opinion, it would be helpful if you would say so.

Popper's logic imposes certain core expectations on scientific debate of which two are relevant here. The first is that a theory should be articulated with sufficient precision that it can make testable predictions. In other words, a hypothesis is not worthwhile unless it is at risk of being refuted. You may not construct a hypothesis that is so general or unclear that it is immune from contradiction and apparent contradictions should be addressed. Second, alternative theories should be acknowledged and the reasons for rejecting them given. My aim is to know the reasoning that leads to the rejection of the wave model.

I come now to the Pollard and Borisy paper. You seem to feel that this paper is relevant yet it does not mention or discuss the wave model at all and does not seem to imply any reasoning process that might make predictions that could contrast it with the wave model. I would like to know of behaviours, found in living cells, that are explicable or predictable from this kind of cytoskeletal model and but which are uninterpretable in terms of analogous wave models.

The Pollard and Borisy paper describes an elaborated form of the cytoskeletal model for cell structure and function. Its substantial content is mostly just pen and ink drawings and the evidential status of the various features found in those drawings is unclear. I cannot discern any falsifiable predictions this model makes about the behaviour of actual cells. The criticisms Bretscher used to level and such ideas were always valid – which is not to say that his own lipid flow ideas were any better.

For the benefit of people who are not too familiar with cells, I would like to give a picturesque summary of the ideas underlying Pollard and Borisy's version of the cytoskeletal model. Imagine that the cell is a tent. The cell's outer membrane is a cloth and the cytoskeleton is an internal framework across which the tentcloth is stretched. This paper asserts that the cell moves by disassembling this internal framework at the back of the cell, transporting the disassembled components to the front of the cell, and then reassembling those components. It is, I think certainly true that such a mechanism would move a cell but I do not know of any species that moves by any similar type of mechanism. I therefore find this kind of suggestion fanciful. (Other versions of the cytoskeletal model have the cytoskeletal filaments behaving rather like railway lines with engines running along them and carrying cargo. This is equally improbable and parts of it are also implied by Pollard and Borisy's paper.)

But what, exactly, does Pollard and Borisy's description predict? It does not seem to predict whether cells have waves or whether external particles will move backwards, forwards, round in circles or not at all. So it has nothing to do with the wave model. It does not seem to predict whether external particles will adhere to the cytoskeleton. It offers no clue about why cells move or how they decide the direction of their motion. I don't see how it leads to any reasoning process able to produce testable predictions and, hence, I don't see it as a hypothesis. In what ways does this work articulate a theory of cellular action at all?

As indicated above, I will shortly return to this topic but I invite Dr. Richard to look at the tent analogy above. I ask him to add to it, modify it, suggest an alternative, simple description that gets at the nub of mechanism he seems to believe in. I ask him to describe that mechanism, in the simplest possible terms, and to indicate the reasoning process whereby it can lead to testable predictions. I also ask that he address the wave model, which is what this thread is intended to be about. If he rejects that model, would he please explain the basis for that rejection?


I appreciate that this is an internet forum, and not a cell biology conference, but your approach to the various requests for further evidence which would support the wave model is rather strange. Dr Richard has cited a Cell review, wherein the authors marshal a large body of evidence in support of actin assembly/disassembly as a mechanism for motility. A "pen and ink" cartoon is presented, along with electron micrographs that appear to support it. A mathematical model is outlined which predicts the observed behaviour of cells. Primary literature showing that pharmacological or genetic disruption of the normal function of the cytoskeleton results in impaired motility is discussed. It is, in short, a fairly compelling case.

You have countered it by giving a lecture on Popperian philosophy and drawing an analogy with a tent. The evidence for the wave model, as published on your website, seems similarly reliant on analogies and personal incredulity.

Can I ask, why did the lukewarm reception of your hypothesis not lead you to devise and carry out experiments to test its predictions? Why did you instead declare the scientific establishment liars and frauds in a book? Why not rub their noses in their misjudgement by presenting a devastating case for the wave model?
 
I appreciate that this is an internet forum, and not a cell biology conference, but your approach to the various requests for further evidence which would support the wave model is rather strange. Dr Richard has cited a Cell review, wherein the authors marshal a large body of evidence in support of actin assembly/disassembly as a mechanism for motility. A "pen and ink" cartoon is presented, along with electron micrographs that appear to support it. A mathematical model is outlined which predicts the observed behaviour of cells. Primary literature showing that pharmacological or genetic disruption of the normal function of the cytoskeleton results in impaired motility is discussed. It is, in short, a fairly compelling case.

You have countered it by giving a lecture on Popperian philosophy and drawing an analogy with a tent. The evidence for the wave model, as published on your website, seems similarly reliant on analogies and personal incredulity.

Can I ask, why did the lukewarm reception of your hypothesis not lead you to devise and carry out experiments to test its predictions? Why did you instead declare the scientific establishment liars and frauds in a book? Why not rub their noses in their misjudgement by presenting a devastating case for the wave model?

I presume you didn't bother to read chapter 7 of my site, which lists the evidence supportive of the wave model.

The point of Popper's logic, which you also ignore, is the need to cite negative, refutational evidence. The evidence refuting the cytoskeletal assembly model was cited on my web site - in some detail. I found it a shame that Dr. Richard was unable to find a review that addressed such lines of evidence and argument. I also found it a shame that he could find no paper that addressed the wave model which, along with the evidence that bears upon it, is the topic of this thread.

Re your comments. Mathematics is a tool, it not a source of evidence, the micrographs shown in their paper have no obvious bearing on the mechanism these authors proposed. Furthermore, pharmacological or genetic disruption of motile proteins would be expected to disrupt cell motility regardless of its mechanism.

It is not my wish to attack Pollard and Borisy but their paper does not present anything resembling a scientific case. There are literally dozens, possibly hundreds of similar papers but the fact remains, this discussion is about the wave model and the evidence that bears on it, be it positively or negatively. Viewed in that context, their paper ignores evidence, alternatives and counterargument but I would not hold them especially culpable in that.

I do accuse my former colleagues of fraud and deceit, not simply because they engaged in such reviews but that they continued to do so into the teeth of protest, perfectly clear theoretical arguments and perfectly clear, observational evidence such as that listed on my site. Such conduct is not only discourteous, it is not science or logic by any criterion I will accept.

I note that you do not refer to the evidence for the wave model or the refutations of the cytoskeletal model given in earlier chapters. As for your suggestion that I return to the laboratory and perform my own experiments - it seems to me that the evidential status of this field is perfectly clear and I see no purpose in reinventing the wheel. I would certainly not do so merely to entertain the kind of people who calculatedly ignore what is said to them.
 
John,

You have not given us any predictions from the 'wave model' that would yield experimental distinction from the 'cytoskeletal model'.
 
I appreciate that this is an internet forum, and not a cell biology conference, but your approach to the various requests for further evidence which would support the wave model is rather strange. Dr Richard has cited a Cell review, wherein the authors marshal a large body of evidence in support of actin assembly/disassembly as a mechanism for motility. A "pen and ink" cartoon is presented, along with electron micrographs that appear to support it. A mathematical model is outlined which predicts the observed behaviour of cells. Primary literature showing that pharmacological or genetic disruption of the normal function of the cytoskeleton results in impaired motility is discussed. It is, in short, a fairly compelling case.

You have countered it by giving a lecture on Popperian philosophy and drawing an analogy with a tent. The evidence for the wave model, as published on your website, seems similarly reliant on analogies and personal incredulity.

Can I ask, why did the lukewarm reception of your hypothesis not lead you to devise and carry out experiments to test its predictions? Why did you instead declare the scientific establishment liars and frauds in a book? Why not rub their noses in their misjudgement by presenting a devastating case for the wave model?
Why answer the questions if you can avoid it?
 
John,

You have not given us any predictions from the 'wave model' that would yield experimental distinction from the 'cytoskeletal model'.

For most purposes, the cytoskeletal model is insufficiently specified to make any predictions; that is, it is largely vacuous and every observation tends to be interpreted as support for it.

In a couple of respects, it has intrinsic assumptions which seem testable. For example, since the cytoskeleton is an internal structure and capping and particle movement occur on the external surface of the cell, that theory seems to predict that some cross membrane link must be forming. This has been tested using patches formed from external glycolipids, external synthetic lipids and membrane proteins which are known not to traverse the membrane. Because the internal chemistry of the membrane is chemically uniform, one would not expect any cytoskeletal components linked to the membrane to be able to distinguish these from general components of the membrane. Thus, by the cytoskeletal model, they should not cap but they do.

Further, in general, if the cytoskeletal model were correct, one would expect to see some kind of chemical specificity in the type of particles that would move. Actually, their chemical nature seems to have little effect, the main thing is size. The cytoskeletal model does not obviously predict any such size dependency.

In addition, exogenous particles seem to begin moving immediately after contacting the cell surface, certainly within a few seconds. By contrast, the accumulations of cytoskeletal components under (some) of these particles takes several minutes to occur. Those accumulations were widely cited as evidence for the cytoskeletal model but, so it seems to me, the time factor says otherwise.

Bretscher used to point these kinds of thing out and there was never anything wrong with his criticisms. The present ascendancy of the cytoskeletal model arose because Bretscher's flow model was disproved. His criticisms of the cytoskeletal model were never answered. My point is that both sides of that debate ignored the wave model and should not have done so.

There are observations which seem to support the wave model and are very hard to interpret in terms of the cytoskeletal model. The are listed in chapter 7. Perhaps the clearest are the saltatory (stop start) motions and occasional retrograde motions seen in moving particles. Retrograde means that a particle is moving along, stops, briefly reverses direction, stops agains and then proceeds in its original direction. Such observations are easy to interpret in terms of the wave model while the cytoskeletal model just does not predict anything like that.

Another observation supportive of the wave model is the report of particles moving "in concert" with the "dramatic waves" seen on fish keratocytes. These cells seem to be a particularly active type and were used by Sheetz in some classic studies in "Nature". Such observations look very close to being a direct demonstration of the correctness of the wave model. However, I need hardly say that the authors did not attempt to interpet them.
 
Reply to Dr. Richard part 2

But John, all you have done is outline a theory. It is fine as a hypothesis, as is the alternative baked bean cell movement theiory I have just invented.

If you want to convince me, do some experiments to show us cells moving using the waves you describe.

While you are doing this, please may I present an alternative hypothesis that has had some nice experiments done to support it:

Cellular Motility Driven by Assembly and Disassembly of Actin Filaments

What, specifically, do you disagree with in this article? It seems to me it gives a coherent picture of how the cytoskeletal model can drive cell movement.



Observational evidence and the degree of certainty that can be ascribed to it. What kinds of observational data to trust.

There is a common, apparent belief that scientists gather neutral data, more or less at random and a theory will emerge from the data but this not true. In Popper's logic, the best experiments, the critical experiments, are those that can decide between two hypotheses. A critical experiment is one that should produce different outcomes for different hypotheses and so allow them to be distinguished. In other words, a critical experiment is an interpretable experiment. Many of the published observations in this field are not such as to enable one to distinguish the different theories.

There is no such certainty surrounding the cytoskeletal model. As a theory it is largely vacuous and makes very few predictions. Consequently, it is hard to identify any experiment that critically distinguished the cytoskeletal model from any other. Where the cytoskeletal model is testable it has been tested and it has been refuted. Those refutations have not been answered, they have been ignored.

Advocates of the cytoskeletal model display a pronounced confirmation bias in interpreting their own observations. Thus, even when an experiment has no power to distinguish hypotheses, the results will be hailed as confirming the cytoskeletal model. In other words, they cite as evidence for their own ideas results that in no way compete with alternatives. Thus the Pollard and Borisy paper and the comments from Cynric claim that the cytoskeletal model is confirmed because agents that disrupt the cytoskeleton will stop capping and motility. Well, it's true that the cytoskeletal model does predict that such disruption will disrupt capping and motility but why, I wonder, do people make this claim when all the models make the same prediction? We already know that capping and particle movement are linked to motility – this is part of the body of facts to be explained and one would reject a theory where that was not true. So, whatever the mechanism of motility might be, it is obvious that agents that stop motility will also stop capping and particle movement. And yet, over and over again, advocates of the cytoskeletal model trot out this sort of fallacious claim. In short, the cytoskeletal model does not offer a validated description of cell movement. Neither does that model cohere with well established, secure scientific results.

Once one has a result, one can increase the certainty in the data by repeating the same or very similar experiments but one cannot thereby increase the certainty of the interpretation. Security of interpretation comes about when several different types of observation all point in the same direction or when a hypothesis makes an apparently unlikely prediction which is subsequently confirmed by observation. It is hard to identify a single critical line of evidence that does support the cytoskeletal model.


Secure interpretations are well-established ideas such as evolution, thermodynamics etc. The ideas that come under the heading of "the cytoskeletal model" are in no sense secure and, if its premises have ever been stated, those premises are not some unchallengeable base from which to build further interpretations. For example, the idea that contractile proteins generate physiologically relevant forces by assembly and disassembly is not a secure fact. – it is something that must be justified by *clear* observations whose interpretation are beyond dispute.

By contrast, the assertion that muscle proteins are contractile and generate force by that contraction, or that waves exist in cell membranes, are completely secure facts and these are premises of the wave model. I believe I have every right to use them as inputs into and as evidence to support my own theorizing.

Finally, I would like to make a general comment about Popper's work, which I regard very highly and as seminal to an understanding science and the nature of logic. Nonetheless, I am aware that monay other workers act as if they believe Popper and his logic are nonsense - a tiresome interference with the *real* science that they do. In fact, there are grounds for thinking that people in general, not just scientists, have a problem with Popper's work. Some readers may know that there have been many psychological studies performed into the way people use Popper's logic. They can be found under the generic name "the Wason task," being named after Peter Wason, the UCL psychologist who initiated them. The general conclusion that emerges from these studies is that people very often seek confirmations of their own beliefs and are reluctant to seek discomfirmatory evidence, especially as it applies to their own preconceived ideas. People are cognitive misers who take the easy route in their thinking, looking for new approaches only when they cannot avoid doing so. This is the kind of thing leads to the phenomenon of confirmation bias.

The social psychological studies of Milgram, concerning authority, and Asch, about conformity, are also relevant in this context. People stick with their groups and conform to group beliefs, even when contrary evidence is perfectly clear. It does seem to me that this sort of thing occurs in science.
 

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