Cells, Gels and the Engines of Life

The most engaging science books tackle the narratives that scientists believe and on which they base study designs and interpretations. This book provides a detailed case study of how such scientific stories and simple mental images operate to guide entire fields over decades - and not always along the best available paths. This book questions a whole list of "textbook" fundamentals and offers an alternative, integrated framework for explaining a wide range of cell functions. Once a misguided view has been established in any field, it can take a rare blend of courage, expertise, and clarity to budge things in a new direction. Anyone with a firm reading ability can delve into this book and might be surprised, given the school-inflicted association of basic science instruction with soporific textbooks, to be sucked in on the first page. This is much more than a book about how cells work; it is a master class in fresh and precise scientific thinking, an art much in need of renaissance in an age of truth by click-through count, research-grant total, and mere widespread assertion. Pollack starts by peeling back layers of decaying assumptions about the functionality of the living cell, showing how each narrative twist was constructed to salvage some older assumption that was in danger of withering before new evidence. A cell "wall" was originally imagined long ago as being needed to keep the cytoplasmic "aqueous solution" within the cell; otherwise, the cytoplasm would surely dissipate into its surroundings. Eventually, though, a long series of problems with that story began to emerge. But instead of killing the story, each new problem elicited a patch to salvage the old model. First, certain ions had to move into and out of the cell. So to get ions moving in, some "channels" through this "wall" had to be postulated. Then, to get them moving out again, we needed some "conveyers." Researchers gradually discovered more and more substances of myriad shapes and sizes moving into and out of cells in an epic dance. Many of these substances were also staying either inside or outside in precise ratios. The "channels" and "conveyers" that would be needed to make all of this happen started to multiply beyond the wildest nightmares of a factory-automation engineer. Moreover, the energy that would be required to keep all of these imagined mechanisms running seemed to far exceed the available supply. Pollack likens this situation to the crisis of the old geocentric model of the solar system, the one that tried to explain the impossible, winding orbits of planets around the Earth. As it turned out, of course, those orbits appeared so wildly intricate because they weren't orbits around the Earth at all. Likewise, according to Pollack, the mind-boggling complexity of conventional cellular channels and conveyers has become the crisis of the old story of how cells work. He makes a detailed case that this old picture is misdirected at virtually every step and should be updated by looking with fresh eyes at newly available research while revisiting some older views that were trampled under and mostly lost in the march of scientific "progress." A major source of challenge for the old story, with its central role for the cell wall, is a broad pattern of experimental results in which cell membranes are destroyed or removed and ... nothing much happens (at least not for hours or days). This makes it clear that something else is also at work, but what? Pollack outlines a new model that begins with the fundamentals of how proteins, water, and ions interact at a chemical level. By this time, he has posed some other puzzling questions about cells. Among them, why do they only freeze at temperatures much colder than expected based on their chemical composition alone? It turns out that the cytoplasm is no "aqueous solution" at all, Pollack argues. However, the idea that it is, first made well over a century ago, set the entire field down a misleading path. Instead, cytoplasm is a gel, and one of the long-missing pieces of the cytoplasmic-gel puzzle is structured water (watch his University of Washington Annual Faculty Lecture on structured water). Pollack argues that much of the water within cells is not mere "bulk water" (random molecules in liquid state). Rather, water can structure itself into an ordered grid that builds on charge patterns on protein surfaces. Cytoplasm is infused with a fine interior latticework, the surface area of which amounts to 100 times the surface area of the cell membrane. Structured water lines up along these internal lattice surfaces. This is far from the conventional view of an intracellular solution in perilous need of being held in by a retaining wall. Pollack identifies structured water as a fourth state of matter between normal liquid water and solid ice. Structured water helps explain the odd resistance of cells to freezing. Water molecules are dipolar and can arrange themselves in grids with varying degrees of depth. These structured grids can also rapidly "destructure" as soon as conditions supporting structuring collapse. Triggering sudden destructuring events turns out, according to Pollack, to be one of the key mechanisms through which cells get their work done. Dispensing -- for the moment -- with "channels," "pumps," and "conveyors" of any kind, Pollack is able to show how sodium exclusion, potassium inclusion, and the negative electrical state of cells can all be explained "directly out of the physical chemistry of these ions in relation to the cell's water and proteins." Moreover, unlike previous convoluted explanations, "the system is in equilibrium. No energy is required for its maintenance. No special widgets are needed to keep potassium inside the cell or sodium outside the cell -- all of this follows directly from the cytoplasm's basic physical chemical features" (97). He observes that, "the paradigm offered here is... worlds apart from current views which place most of the action in the membrane instead of in the cytoplasm" (109). Pollack finds the locus of most cell activity and function in the general phase-transition properties of gels. He cites the practical use of phase-transitioning gels in engineering and presents evidence of similar mechanisms at work in the major functions of cells. In phase transitions, "triggering is `razor-edge.' Nothing happens until a threshold is crossed, whereupon contractile action [in muscle cells in this case] is massive" (233). He returns to engineering to note analogs of cellular phase transitions in modern technological innovations that go well beyond conveyors. He explains cellular transport along actin chains as using a "moving melt window," noting that the same principle is used in "zone refining" crystals, which enabled the creation of the first germanium transistors (174-75). After chapters with details on cellular phase-transitions, comic relief arrives when a subway map from the "Cellular Transit Authority" introduces the chapter on transport mechanisms: "We realize you have a choice of fundamental biological hypotheses; we'd like to thank you very much for riding with us." The book then examines how cells move materials from place to place using phase transitions. Pollack next discusses more specific transport mechanisms that at first might seem to harken back to the old "conveyers." By now, however, he has deeply reconceived such mechanisms in a new context -- they use the same phase-transitions described in the general case of the cytoplasm, just in more specific ways. Thus, a "propagating phase transition" passes along actin bundles and microtubules, which are selective about which materials they transport -- and in which direction. As for other transport tasks, even moving whole cells around using cilia and flagella, "the presence of extracellular transport tasks need not imply fresh principles, for the relevant machines are built of the standard parts" (197). After discussing cell division, Pollack hypothesizes that the degree of water structuring within cells may be a key mechanism in cancer. Water disorder promotes cell division. Mutant proteins in cancerous cells are more likely than normal proteins to promote water destructuring. This destructured-water environment may well play a role in stimulating the excessive cell division seen in cancer cells. Therapies directly targeting mutant proteins have already shown efficacy as cancer treatments (221-22). An important recurring theme in the book is that a field can regress. A misleading paradigm can invade and occupy a field and push out a more correct paradigm, taking the field backwards. Pollack reports in the chapter on muscle contraction that, "until the mid-1950s, muscle contraction was held to occur by a mechanism similar enough to the one that will be suggested here that it must be considered a progenitor. The dominant feature was protein folding" (226). But two studies then found evidence of a "filament-sliding" mechanism at work, and this came to replace the earlier protein-folding hypothesis. While the new evidence did not really negate the old model -- it should have enhanced it instead -- the protein-folding model faded before the popular new filament-sliding model. Pollack details the serious problems with the filament-sliding and accompanying "swinging cross-bridge" theory of muscle function and then picks up "where the pioneers of a half-century ago left off." This time, though, the once and future protein-folding model will "not only be required to fit this older evidence, but also the evidence of the intervening years that has come to be considered supportive of the current sliding paradigm" (229). Similarly, Pollack eventually combines key elements from both new and old visions in the case of cell membranes. By the end of the book, a complex cellular barrier zone that includes re-visioned structures that roughly correspond to the old pumps and channels return. However, due to the high explanatory power of gels and phase-transitions, the roles of barriers and channels "may be less specific and less central than generally envisioned" (276). By this point in the book, this comes across as a studied understatement relative to the weight of evidence that has been presented undermining simple conventional images of cell walls and channels. Another treat comes in the discussion of cellular energy production. The basic engine of cellular energy is likened to a process of setting up and knocking down rows of dominoes. The bulk of effort goes into creations of order, essentially setting up dominoes in a row. This order can then be released, creating a rush of work energy with the mere touch of a finger (phase-transition trigger). Cellular work energy derived from sudden controlled-chaos events are only made possible by previous build-ups of order. Energy is thus "stored as order" in cells, with structured water playing a key role in forming the order that is "destructured" in a sudden phase transition. The final chapter summarizes all that is different in the paradigm Pollack presents from conventional textbook views of cellular function. It concludes with additional applications and observations. He notes, for example, that the conventional understanding of how plants can draw water up to impressive heights (as much as 100 meters in the case of redwood trees) remains vague. Yet if the water within xylem tubes is structured and not merely in the form of bulk water, "if the water clings to the matrix, column weight is irrelevant: So long as there is enough adhesive force, a sufficiently long tube could deliver water to the moon" (271). While quite readable, this is no New-Age-ish pop-science book. It is tightly research-based, yet remains as clear as it can be for the general reader relative to the depth of content. True principles visible in one place often have analogs elsewhere and Pollack is not afraid to note them, yet one can sense the care and precision with which he does so. He keeps his hypotheses tight and specific and asks his questions step by step, proposing possible answers based on a global research literature spanning decades. Pollack also does not skim over the nuts and bolts of the old paradigm in favor of the temptation of engaging with straw men. He encourages his audience to read standard textbooks on cellular function to get a sense of the conventional story on its own terms. In his book, though, he presents the evolution of that old story as a step-by-step historical process, lets that stand in all its duct-tape-the-old-paradigm glory, and asks if there is something wrong with it.

This book is heretical and courageous, and - if it can escape burning - may become a seminal landmark in our understanding of living systems. Based to a large extent on the pioneering (and often unfairly derided) work of Gilbert Ling, the book focuses on the importance of the gel-like nature of living cytoplasm - the interior of living cells - at the expense of the vaunted cell membrane. It turns out that cells can do fairly well without intact cell membranes because many functions attributed to the membrane are actually accomplished by gel properties of sub-membrane cytoskeleton of actin, microtubules and other protein structures. Pollack provides evidence that patch clamp techniques, which claim to study isolated membranes (and have provided much of the "evidence" for membrane ion channel and ion pumping mechanisms) include sub-membrane actin cytoskeleton which, according to Pollack, is actually regulating ionic fluxes and concentrations. The book describes how cytoplasmic gels manifest collective phase transitions such as polymerization of actin proteins with accompanying ordering of cell water and exclusion of large cations. According to Pollack, these collective phase transitions can explain not only ionic fluxes, but also voltage gradients, propagating action potentials, mitosis, muscle contraction and cell movement. Ion channels and pumps are not mythical, but overstated. Pollack traces the roots of (in his view) the "membrane-centric" misconceptions and his proposed revolution is believable. Our cells are not bags of liquid governed by membrane activities, but protein matrix-based gels covered by a thin semi-permeable membrane "skin". The cytoplasm is intrinsically reactive and able to maintain cell homeostasis and functions. The cytoplasmic gel best captures the essence of the living state. Molecular biologists, biochemists, membrane physiologists and others will no doubt gnash their teeth over this book, and many will dismiss it out of hand, citing ever-expanding knowledge in their respective fields. However ultrareductionist "bind and grind" techniques quite often fail to see the forest for the trees. Pollack encourages readers to compare his ideas to conventional approaches as espoused in mainstream textbooks. Any objective biologist should do so. The book is easy to read, clear and understandable, and well illustrated with simple diagrams. Those willing to curb their dogma will find it stimulating and delightful.

Great information, really helped further my spiritual & healing journey!

Pollack's theory, backed by a whole host of experiments, is totally fascinating. He very respectfully points out the gaping holes in current theories about cells and how biological processes are supposed to work, and it all centers around the concept of "structured water". The only reason I couldn't give the book 4 stars is because it does get pretty technical in the middle. The book is sort of a cross between a university textbook and a "science for the informed layperson" kind of thing. Nevertheless, I read through to the end and I wasn't disappointed. If Pollack is correct even 10% of the time, the ramifications are staggering. Highly recommended. Now, if I could just get hold of a copy of The Fourth Phase of Water...

As a non-biologist (nuclear chemist/experimental physicist) I read Dr. Pollack's book with interest, in 2006, and found it relevant to our work - and plausible. However, I made a mistake and read a review, by apparently a fellow Faculty (Alexander Stein), enclosed below. Reading it - peremptorily, admittedly - I decided not to learn more about biology... Recently I found out that Dr. Pollack got the highest reward from his fellow Faculty for his research. By the way, it still is very relevant to our research. We do plan to pursue it. It's true I should have gone deeper into this - but one simply cannot do everything. The way Amazon manages these reviews is flawed ("the highest and the lowest"). Perhaps there should be a warning that there is a significant probability that some reviews may not be done in good faith. The flawed review: "Dr. Pollack is an embarrassment to his field and his University. This book is a collection of old results (from as far back as 50 years ago) that puzzled the world's scientists at the time they were first published. There has been much progress in the intervening decades that Dr. Pollack would do well to read and understand. All of the ancient science upon which..." Robert F Holub Research Professor CARES, Clarkson University Potsdam, NY

Gerald Pollack is a genius, and a man of integrity. I studied old school cell biology and chemistry that failed to adequately explain the reason why cellular functions occured. Of course we know capillary action occurs. Of course we all know cells divide and spindles get created as if by magic. What the old textbooks never explained in any believable fashion was HOW? WHY? Light bulbs went off in my head when I read this well illustrated, clearly written book of some seminal thinking. Thank you Dr. Pollack for a fascinating and readily understandable treatise that's radically improved my understanding of life's processes.

Whew. I think this is probably correct as the biology models were just too orderly. So much organization in such small structure! Or is that structure a tattoo on a different reality which is much deeper. If I had to guess, my guess is that this is correct. If not, it at least saved me from seeing everything everywhere all at once...

I took a course in Cell Biology in college a few months before reading this book. It would be useful to know something about cell biology from a textbook standpoint, before reading this book. This book tells us much that the textbooks do not tell us about living cells. It explains where many of the propagated models fall down. Then it gives a more logical model based upon actual observed experiments. (I strongly also recommend The Fourth Phase of Water by the same author. It was written 15 years later, so it includes more recent data.)

This is an easy to read explanation of an innovative hypothesis for how cells work. The style of writing makes the explanations clear and combined with the excellent illustrations provides a compelling argument. Definitely worth reading and giving serious co sideration to.

I have some questions about the standard cell theory. The main question is the theory of ion pumps. Active ion pumps are used to maintain concentration gradients inside and outside cells. I don’t have a sense of the magnitude of energy cost. But intuitively I feel it must be very energy intensive. Is there a more economic way to maintain such cellular structure? I searched for some answers on the internet. Initially I found the name of Gilbert Ling. But his writings are too technical for me, a person with little relevant background. Later I found this book by Gerald Pollack. It introduces the ideas of Gilbert Ling and others in a very intuitive way. The book can be roughly divided into two halves. The first half is about cell structure. The second half is about cell function. The theory of cell structure is association. The theory of cell function is phase transition. Let me explain these ideas briefly. A Na+ ion is smaller than a K+ ion. Since a Na+ ion is smaller, it has stronger electric attraction to water molecules, which are polarized, than a K+ ion. As a result, a Na+ ion, together with the attracted water molecules, as a unit, is larger than the unit of K+ and associated water molecules. This is the main idea of association principle. We need to look at ions and atoms in association. We can’t treat them as independent particles. Most proteins are negatively charged. There is a natural affinity between proteins and cations, such as Na+ and K+. But the levels of attraction are different. A K+ ion unit (together with associated water molecules), being smaller than a Na+ ion unit, has stronger affinity with proteins. There are a lot of proteins inside cells. They attract more K+ ion units than Na+ ion units. This explains why the concentration of K+ inside cells is higher than the concentration of Na+. It is a simple explanation. It doesn’t need energy intensive ion pumps. This is a brief summary of the first six chapters. Chapter seven is about cell potentials. The explanation is less convincing to me. I have to reread it later. Overall, the first seven chapters constitute the first half of the book, which is about the cell structure. The second half is about the mechanism of the cell functions. It is phase transition. Let me briefly go over its intuition. Suppose the temperature of the water is at 99 degree. You turn on the heat a little bit. The water temperature rises to 100 degree and water boils. The boiling water generates a lot of steam, which has tremendous propelling power. At phase transitions, great powers are released, which can be used to perform various cell functions. Phase transitions can be triggered by the changes in temperature, in electric charges, or ph levels. The idea is that many parts of cells are near phase transition conditions. A small change of the environment, such as the addition of a small number of ions, will generate phase transitions and hence cell actions. A protein filament can be in a coiled state or extended state. The transition from the extended state to coiled state represents muscle contraction. The transition to the other direction represents muscle relaxation. The idea seems to make sense. The book contains many examples that make cellular functions much easier to understand and much less mysterious. I will go over some examples about ions. Most proteins are negatively charged. Most messenger cells, such as histamine and adrenaline, are positively charged. Positive charged messenger cells have an easier time to connect with proteins, which are often negatively charged. Divalent ions, such as Ca2+, can act as zippers, to seal two protein structures. Two positive charges of Ca2+ can attract two different protein molecules and seal them together. That is why Ca2+ ions are important in controlling the operation of molecular gates and channels. Before I don’t understand what is special about Ca2+, why Na+ or K+ can’t perform the same functions. This book introduces a non-orthodox way to understand cell structure and functions. When one presents a non-mainstream theory, he has to make extra effort to make his message clear. Whether you agree or disagree with his ideas, you can learn a lot from this book.

Tout est dans le titre de ce commentaire. Vous voulez révolutionner votre connaissance des mécanismes biologiques, et prendre une bonne longueur d'avance sur les recherches en cours : lisez-le !

Very Good product

Agradecido por conocer los planteamientos y descubrimientos alrededor del agua