Membrane theory and the decline of scientific method

[Vladimir Matveev]

Membrane theory and the decline of scientific method
Nanometer-minded persons in science

V.V. Matveev and D.N. Wheatley. "Fathers" and "sons" of theories in cell physiology: the membrane theory. Cell. Mol. Biol., 51(8): 797-801, 2005.

Abstract. The last 50 years in the history of life sciences are remarkable for a new important feature that looks as a great threat for their future. A profound specialization dominating in quickly developing fields of science causes a crisis of the scientific method. The essence of the method is a unity of two elements, the experimental data and the theory that explains them. To us, "fathers" of science, classically, were the creators of new ideas and theories. They were the true experts of their own theories. It is only they who have the right to say: "I am the theory". In other words, they were carriers of theories, of the theoretical knowledge. The fathers provided the necessary logical integrity to their theories, since theories in biology have still to be based on strict mathematical proofs. It is not true for sons. As a result of massive specialization, modern experts operate in very confined close spaces. They formulate particular rules far from the level of theory. The main theories of science are known to them only at the textbook level. Nowadays, nobody can say: "I am the theory". With whom, then is it possible to discuss today on a broader theoretical level? How can a classical theory - for example, the membrane one - be changed or even disproved under these conditions? How can the "sons" with their narrow education catch sight of membrane theory defects? As a result, "global" theories have few critics and control. Due to specialization, we have lost the ability to work at the experimental level of biology within the correct or appropriate theoretical context. The scientific method in its classic form is now being rapidly eroded. A good case can be made for "Membrane Theory", to which we will largely refer throughout this article.

Find full text here:
http://www.actomyosin.spb.ru/fathersandsons.htm

The illustration for the article:
http://www.bioparadigma.spb.ru/images/F ... d.Sons.jpg

[Hardstreet]

Since when are membranes a "theory," and since when must biological theories be based on "strict mathematical proofs"? I'd say that it's extremely rare for biological theories to be based on strict mathematical proofs; the only example that comes to mind is the Hardy-Weinburg theorum, although I'm sure there must be other examples.

[BioWizard]

The way I see it, specialization doesnt abolish the ability to theorize. Quite the contrary. It opens up a whole new level of detail. I agree however that there is no more space for the kind of theoretical speculation/philosophical musing done by the philosophers and early scientists in the past, but that's only because our knowledge based has increased significantly. When scientific fact replaces speculation, science moves on to the next problem, unwrapping the workings of biology, one layer at a time.

I do however believe very strongly in interdisciplinary discussion for the sake of appreciating big pictures (which is one of the main goals of this website). Most of the scientists I work with are not interested with much beyond the set of proteins or genes they have specialized in. That doesnt mean however that science as a whole is facing a crisis. I see it as having more "technicians", not less "scientists" (No offense intended to anyone).

Oh and by the way, what is a theory of the membrane? Bilayer lipid mozaic model? That's what you want to dispute? Didnt enough time and work go into validating that model? Why waste more time on something that has been extensively examined? Wouldnt that bring science to a standstill?

[darwinlemmings]

I like your style of writing... also the painting... awesome! What I don't understand is why you think the scientific method is "eroding." Also, what exactly is the membrane theory? When I checked out the link it was exactly what you posted and a picture.

Ohh... Welcome to the forums! :)

[Vladimir Matveev]

My answers to

BioWizard: It is possible to ideate two situations. (i) Einstein theory with a lot of details, and (ii) a lot of details without the theory. Cell physiology, I think, has put in the second situation.

BioWizard and darwinlemmings:
"...what is a theory of the membrane?"---I recommend the references:
http://www.bioparadigma.spb.ru/files/Li ... unking.pdf (article),
http://www.bioparadigma.spb.ru/files/Li ... Viewer.rar (book)

darwinlemmings: the scientific method is eroding because you can not check some theory if you know a lot of details only. Some theory can be checked by itself or by another one, not by "facts". What about this?

Thanks

[BioWizard]

Ok, let me put it this way. Can you please state your theory of the cell membrane in physiology?

[Forest_Dump]

I have been thinking about this a little. Although this specific topic is well outside my field, as a rule, following Kuhn's ideas, the "theory" is what tells you just what counts as relevant data and why, guides you in deciding what further experiments you should or could perform and why, allows you to state that your conclusions or results may have some application beyond what you are doing, etc. Without a theoretical framework, how would you decide whether "cell membrane theory" (and your critique) should be generated in a biology lab, a nuclear physics lab or a history seminar?

Sounds to me like (as Bio noted above) you are so deep within the technical details, you are just unaware of the overall theoretical framework. This is actually not at all uncommon. In many branches of science and for most people who operate in sciences, most of the time, what Kuhn called "normal science" prevails. When working within "normal science", most people go about their problem and puzzle solving, following routine methodology (a little Feyerabend here) and following what seems like the "common sense" of the craft. But, and as a consequence, these people may well be completely unaware that the problems and methodologies employed stem from the theoretical paradigm they work in and the "common sense" is a direct product of working for extended periods of time within and without really critically considering that theoretical paradigm. As I said, not at all unusual.

[BioWizard]

I agree with all that Forest. However, I yet have to find out what a new theory of the membrane entails.

[Vladimir Matveev]

To BioWizard: Modern membrane physiology is a physiology of soap bubble. We need in physiology based on inside structure of the living cell. Some ideas for this you may find in my article: Vladimir Matveev. Protoreaction of Protoplasm. Cell. Mol. Biol. 51(8): 715-723, 2005.

See full text here:
http://www.actomyosin.spb.ru/protoreaction.htm

[darwinlemmings]

Ohhh... are you talking about the whole thing with studying bubbles to get an idea about primitive cells?
8) thats cool 8)

[Vladimir Matveev]

If you study bubbles only you will get nothing...

[BioWizard]

Modern membrane physiology is a physiology of soap bubble.

That's not true. I've seen formulas that describe the physical properties of the cell based on cytoskeletal properties. The internal compartment of the cell is no longer considered as a liquid intern of a bubble, but a mesh work of microfilaments, intermediate filaments, and microtubules.

[darwinlemmings]

Study bubbles can get you places! I thought you were a bubblologist too... I must have been mistaken.
But seriously, there are syudies on bubble/lipid like substances that could have appeared on early Earth and have possibly acted as a membrane/cytoplasm of early cells. Some of these bubble things exibit properties of "life" such, reproduction, growth, and an extremely primitive form of metabolism.

[Vladimir Matveev]

To BioWizard: "Cytoskeletal" approaches include basic principles of the membrane theory---free state of K+ into the cell, sieve function of plasma membrane, pumping function for Na-K-ATPase and so on (see http://www.bioparadigma.spb.ru/files/Li ... unking.pdf for more details). Join cytoskeleton to membrane is a contribution of cytoskeletonists only.

To darwinlemmings: Coacervates make the same (see Oparin's works). But they have no membranes with pumps and carriers. All investigate bubbles, nobody investigates coacervates because the physiology MUST BE bubble one. Rescue oneself if you want study coacervates---referees will become angry. By the way, the article about referees:

Pollack GH. Revitalizing science in a risk-averse culture: reflections on the syndrome and prescriptions for its cure. Cell Mol Biol (Noisy-le-grand). 2005 Dec 16;51(8):815-20.

[BioWizard]

What do ion pumps and membrane potential have to do with a mechanical model of the cytoskeleton?

Do you think you can clearly state what theory you are trying to put forth, or otherwise what existing theory you are trying to debunk, and why?

I recently had a course on cell physiology. Not once have I heard the cell be described as a bubble. In fact, I positively heard one of the lecturers stress that the cell cannot be considered as a vesicle, due to the presence of the cytoskeleton which gives the cell exquisite mechanical properties, very different from a simple liposome.

[BioWizard]

Oh and btw, why does anyone need to disprove anything concerning the Na+K+ channel? High resolution structures of most of these channels have been deposited to the PDB, with detailed accounts of the function of these channels using x-ray crystallography and biochemical assays (in vitro). Some of these papers were just published this year.

[Vladimir Matveev]

Dear BioWizard,

Remember this forum on special lectures about membrane potentials and cell volume regulation. To better understand these lectures please read this:

Short extractions from the last Ling's book you'll find here:
http://bioparadigma.narod.ru/hidden_his ... ewbook.htm

These Ling's works are available too:
http://www.bioparadigma.spb.ru/files/Li ... unking.pdf (article),
http://www.bioparadigma.spb.ru/files/Li ... Viewer.rar (book)

Somebody knowing TWO languages BETTER understand the nature of language.

[BioWizard]

Dear Vladimir,

If you cannot sum up what you are trying to say (or at least a glimpse of it) in a single post, I will not spend time sifting through hundreds of pages that I dont yet believe bear any merit for me.

You keep saying that there are many flaws with our current understanding of the membrane. All I'm asking for is to show me one flaw, so I can be convinced that you are on to something there.

I find your analogy with languages a bit inaccurate. There is only one truth, and knowing different theories doesnt necessarily bring you closer to it.

[Vladimir Matveev]

Dear BioWizard,

Yes, there is only one truth but if it is already discovered why science is needed? There is no truth in the front line of research thus there are many points of view on the same subject exist. Discovered truth is used in factories only. Do you want be a worker on some factory, on sausage factory, for example?

You have two ways: to get new scientific ideas, and to save your time. You have chose the last in this case. It's your problem. It's impossible to study science reading abstract only or look at cartoons. It is not needed to sift hundreds of pages. It's quite enough to read few key pages. As Frenchmen say, it is not needed to drink a barrel of wine to understand its taste.

I hope you well understand that I can not spend time in order to pack hundreds of pages in few lines of abstract for everybody who is lazy to read 3 pages.

Good luck!

[BioWizard]

All I asked is for you to point out a single flaw in the mainstream understanding of cell membrane physiology, and you have failed to do that. It isnt about being lazy, but more about you being able to clearly demonstrate your idea(s) on a message board.

If you are a published scientist, you should know that before any journal agrees to publish your work, they ask you to submit an abstract. If your abstract doesnt demonstrate the merit of your work, they wont even ask for you data. Being able to present your case in a couple hundred word is one of the simplest skills a scientist has to have.

I am sorry that you felt that way (and had to call me lazy), but what I asked from you is extremely simple. Present an abstract that is relevant to the science at hand, rather than a philosophical attack devoid of any science.

If you are not willing to type a few words to explain your theory, I doubt anyone will be willing to read 76 pages get to your point.

Yes, there is only one truth but if it is already discovered why science is needed?

I specificially said:There is only one truth, and knowing different theories doesnt necessarily bring you closer to it.

Cheers.

[BioWizard]

In fact, you specifically said that the cell is modelled as a liposome bubble, and I specifically said that it's an outdated model that has long been discarded.

So good luck with your theory, whatever it is :)

[darwinlemmings]

Vladimir,
Wouldn't you rather have someone summarize something into basically raw fact and key information rather than reading an entire book on something that can be summed up easily?

I still don't understand why you think that studying coacervates is such a problem.

[Vladimir Matveev]

BiWizard: "Why does anyone need to disprove anything concerning the Na+K+ channel? High resolution structures of most of these channels have been deposited to the PDB."
***Na+K+ channel has a sense if membrane separates two solutions. But according to Ling' approach cell inside is NOT a solution, it is a gel where water properties is changed as a result of its interaction with proteins. From this point of view Na+K+ channel is not a CHANNEL, it is real protein structure connecting out cell water with inside gel. It is very important difference. Why? Read the references I gave above. So the channel MUST be regarded as receptor (sensor) only. This statement has a lot of sequences.

BiWizard: In fact, you specifically said that the cell is modelled as a liposome bubble, and I specifically said that it's an outdated model that has long been discarded.
***The membrane theory (MT) is 100 years old. Research of cell structure was made independently from MT dogmas. As a result we have a lot of data inconsistent with the theory. Interestingly, who studies cell structure do not know MT exactly; who has established the main principles of MT are now dead.

darwinlemmings: "Wouldn't you rather have someone summarize something into basically raw fact and key information..."
***Some peculiarities of Ling's approach: (i) solutes distribution between cell and medium is ruled by its adsorption (or not) on intracellular structures (high K+ "concentration" into cell is accounted by its binding to proteins, no pumps); (ii) bound intracellular water is a real barrier for extracellular solutes, not a plasma membrane; (iii) ATP is not the main energy source for cell, real source is an energy transformation accompanying the cycle: protein-water-K+-ATP protein + water + K+ + ADP + Pi; (iv) cell has no enough energy to supply even NaK-pump only postulated by MT.

Ling's approach and MT are global theories for cell scale. Therefore more and more questions will appear in your heads, friends. Please read at least few key pages of Ling's papers. It is not needed to become a preacher of Ling's theory. This theory will give you capability (with other knowledge) to understand scientific problems much deeper! Deep understanding of something important is the best aim for all of us.

Good luck!

Once again:
These Ling's works are available:
http://www.bioparadigma.spb.ru/files/Li ... unking.pdf (article),
http://www.bioparadigma.spb.ru/files/Li ... Viewer.rar (book)

[BioWizard]

Ok, now we're getting somewhere that we can discuss specific points. I dont need to look at your references, unless I have to check experimental results.

***Na+K+ channel has a sense if membrane separates two solutions. But according to Ling' approach cell inside is NOT a solution, it is a gel where water properties is changed as a result of its interaction with proteins. From this point of view Na+K+ channel is not a CHANNEL, it is real protein structure connecting out cell water with inside gel. It is very important difference. Why? Read the references I gave above. So the channel MUST be regarded as receptor (sensor) only. This statement has a lot of sequences.

The cytoplasm is not a gel. The cytoplasm is however filled with a meshwork of filamments and microtubules. These networks composed of microfilamments, intermediate filamments, amd microtubules give rigidity to the cell, and give it's cytoplasm gel-like properties. However, this doesnt at all say that the cytoskeleton is not interspersed by a solution, whose ionic concentrations have been worked out to nanomolar quantities. In that respect, the ion channel is actually interfaced by real solutions on both sides.

***The membrane theory (MT) is 100 years old. Research of cell structure was made independently from MT dogmas. As a result we have a lot of data inconsistent with the theory. Interestingly, who studies cell structure do not know MT exactly; who has established the main principles of MT are now dead.

Errrrkaayyy. So why are we supposed to worry about it?

Structural biologists and Molecular Biophysicists dont really care about outdated theories and models. Falsified models are discarded, and then science moves forward. I havent heard anyone nag about Bohr's model of the atom in a very long time.

***Some peculiarities of Ling's approach: (i) solutes distribution between cell and medium is ruled by its adsorption (or not) on intracellular structures (high K+ "concentration" into cell is accounted by its binding to proteins, no pumps);

Not true. Increased intracellular K+ concentrations are caused by K+ATPase, Kir, Kgnc, and othe K+ channels.

(ii) bound intracellular water is a real barrier for extracellular solutes, not a plasma membrane;

Absolutely meaningless. You are not only challenging MT here, but all of chemistry and biophysics. Water cannot act a barrier for a solute (hence the use of the term solute).
The plasma membrane acts as a thermodynamic barrier to charged and/or hydrophilic species.

iii) ATP is not the main energy source for cell, real source is an energy transformation accompanying the cycle: protein-water-K+-ATP protein + water + K+ + ADP + Pi; (iv) cell has no enough energy to supply even NaK-pump only postulated by MT.

Many of these pumps are assisted by other gradients, like glucose or osmotic gradients. The overall is sufficient to drive the translocation of the ion. Everywhere I've read about it, it clearly says that experimental data confirms the molecular mechanism of action. However, you are claiming fraudulent interpretation of data, so I will have to look more closely into the experimental design of those studies, and those of Mr. Ling.

[darwinlemmings]

Vladimir,

YOU CALL THESE "KEY PAGES?!" THE FIRST ARTICLE HAS 76 PAGES! :evil:

[Vladimir Matveev]

To BioWizard: You well understood MT, congratulation. But you do not know Ling's arguments. However you do not need it if MT is Holy Writ for you. Your choice is your fate.

To darwinlemmings: half of the pages is Appendix, do not worry...

[BioWizard]

If the arguements you made here are quoted from Ling's work, I really dont think I should spend anytime reading his papers :)

[Vladimir Matveev]

It's not arguments, it's statements...

[BioWizard]

Well those statements are trying to argue something, arent they? (hint: MT)

[Vladimir Matveev]

Those statements are trying to turn your interest on new approach and ideas...