Cells, Gels, and the Engines of Life


	Published Review Excerpts (Please scroll down for capsule comments) In Cells, Gels and the Engines of Life, Gerald Pollack has done us all a service: he has provided us with a 305 page preface to the future of cell biology which warns us all – students and establishment alike – that there will always be a fine line between understanding and assumption. While our knowledge of the molecular widgets that comprise living cells has exploded beyond our wildest dream, our understanding of cell architecture and the relations between structure and function still remain rudimentary. For example, one mainstream cell biology text-book defines the cell as “a small membrane-bounded compartment filled with a concentrated aqueous solution of chemicals,” like a balloon filled with molasses. In fact, many biologists who work with molecules in isolation still share this view, as do virtually all lay people, including the congressmen and women who decide which science projects the government will invest in. Pollack views this image as a dragon that must be slain and I cannot agree more. ..the revolutionary concept he presents is that the cytoplasm is a gel. At first glance, it would seem that we have merely changed the model of the cell from a balloon filled with molasses to one filled with jello. However, there is something deeper and much more important in his message. While cell biology focuses on the molecular components that comprise living cells, Pollack centers his attention on the water molecules that swell the cytoskeletal gel and which, up to now, have been virtually absent from the cell biology radar screen. Armed with this unifying concept, Pollack takes on the remaining dragons of cell biology and slays them one by one…..He reminds us how we tend to grasp tightly to conventional models, even when confronted by examples of conflicting results. It is hard not to appreciate his point. Many of our current beliefs in cell biology are ephemeral and will undoubtedly be replaced, whether we like it or not, by new and improved views, just like the epicycles which explained the planets’ movements around the earth was replaced by Galileo’s heliocentric model of the universe. In the end, I would say the Cells, Gels and the Engines of Life takes the reader on a voyage through cell biology that is not unlike listening to the team of prosecuting attorneys play out their hand in the O. J. Simpson trial. The evidence laid out before you is shocking, unnerving, even titillating, to the point where it is hard to pull yourself away; at the end, you are so convinced of the defendant’s guilt that you question whether you ever again can accept what you see in the world at face value. The difference in this case, is that we never get to hear the defense’s side of the argument (whether worthy or not). Herein lies both the strength and weakness of this nicely sculpted and wonderfully illustrated polemic against complacency in the cell biology establishment. Donald Ingber, Cell, 2002 Don’t even think of touching this book if you believe that everything about the cell will be understood when the function of every gene and every protein has been worked out ad infinitum, and life itself could then be simulated by the fastest supercomputer. For that’s what we are told by the molecular geneticists who have sequenced the human and other genomes, and are now desperate to find some meaning in it all. Don’t touch this book, because it will destroy your life and puncture your illusions; or at least throw you into a terrible state of self-doubt. If, however, you have been bored out of your mind with the proliferation of lists upon lists of molecular nuts and bolts that simply don’t add up to a whole, and secretly wondering how the cell might really work, then beg, borrow, steal or buy a copy of this book right now. You are in for a big treat. This book will sweep you off your feet. With disarming lightness and charm, Gerald Pollack sweeps aside the big myths out of which the entire subject has been spun, thus disposing of perhaps 99 percent of what one might have learned from cell biology textbooks. It is like having a thorough spring-cleaning done on your mind. The layers of intellectual cobwebs accumulating ever since you decided to read biology - and never really been encouraged to think your way to any modicum of understanding – all cleared away, one by one, until you see sunlight sparkling in your mind’s eye. You’ve regained the innocence of first gazing into life’s wonders, and ready for more. Mae-wan Ho, Institute of Science in Society, 2003 Cells, Gels and the engines of life reads like a novel, and is nicely illustrated by David Olsen to make difficult concepts easier to understand. The presented approach is refreshing and easy to follow by scientists from any discipline and also by those without biological background. We found that the book is also very valuable for graduate students. They love the controversial and revolutionary aspects of the book and it triggers their critical opinion of theories presented in classical textbooks. A new, almost simple, model of the cell based on the idea that the cell is a gel and not an aqueous solution. ….the fact that cell function may eventually be understood from an ordinary chemical or physical point of view is extremely attractive. C. van Donkelaar and C. V. C. Bouten, J. Biomechanics 36: 147-150, 2002 Gerald Pollack has written a rollicking romp through cell biology that should rock the science. He has taken the principles of physical chemistry and applied them to the fundamental process of the cell in a lucid explanation of how these “engines of life” might work. The prose is elegant and eloquent and the analogies are colorful, illuminating, and memorable. … Pollack’s ideas have made me think more deeply about my own science and, I suspect, will affect the thinking of any life scientist with an open mind and a sense of adventure. “Cells, Gels…” is a good read in the sense that you can take it to the beach, or it can keep you up all night. Pollack has gone out on a limb to shake up the status quo of cell biology and for this alone we should be grateful. Felicia Etzkorn, Trends in Microbiology 10(4) April, 2002 …a new and refreshing approach built on fundamental principles of physics and chemistry… provocative in many ways….… beautifully edited with many pictures and photographs, as well as colorful drawings and figures….captivating and recommendable to both graduate and undergraduate students as well as all science professionals with open-minded curiosity. Xavier Gasull, Clin Neurophysiol. 114: 748-750, 2003 If Cells, Gels and the Engines of Life is correct, a large number of biologists should be fighting very scared. According to the author, Gerald Pollack, one of the fundamental concepts of modern cell biology is seriously wrong. Pollack believes that the importance of the plasma membrane has been overwhelmingly overstated, and pumps, transporters, channels, membranes bounding intracellular compartments and suchlike have few or none of the roles that we all ascribe to them. If this is all correct, a tidy proportion of all modern biologists have been wasting their time for the past few years… Pollack’s central hypothesis is that the contents of cells are not aqueous solutions, as biochemists have tended to assume. Rather, the cytoplasm is a complex gel, and much of the behavior of cells can be explained by gel-specific concepts such as phase transitions and exclusion of specific solutes from the gel matrix…. This is the book of someone who knows the implications of what he’s trying to say….The critiques of existing models are strongly argued. There’s no room for the current view to be basically sound, give or take a reinterpretation here and there, or revision of a small subfield. The only answer is a complete paradigm shift, with the old membrane-based framework going out of the window and being completely replaced by a complex and interlocking system of phase transitions in an architecture built from gels….Overall, suffice it to say that I was intrigued, and that I found elements of the argument completely convincing. Robert Insall / Nature Genetics, 2001 For anyone with scientific curiosity who wants to understand better the complexity of the human cell. J. M. Bennett Leukemia Research, 2002 This book is, without doubt, an impressive example of informed scientific dissent. Dr. Pollack has obviously thought long and hard about all these questions; his obvious enthusiasm for his hypothesis is matched by an impressive depth of research, and he is obviously intimately familiar with the seminal works from the last 100 years on both sides of the debate. …Throughout, the author avoids the embittered tone often adopted by those whose cherished theories run against accepted dogma, adopting instead an admirably patient explanatory tone and urging readers to decide for themselves which fundamental hypothesis deserves acceptance. The mechanisms proposed by Dr. Pollack are extremely elegant and well-conceived, and if the abbreviated explanations presented in this review pique your curiosity, be it in the form of inspiration or incredulity, I strongly recommend that you take a closer look at the text itself. A. Oberst, Cell Death and Differentiation (2003) 10: 266-268. Most modern biology books are prescribed by our current excessive-peer reviewed mentality; this book breaks free and challenges many of the sacred cows of cell biology. The author treats the cell as a gel and believes that our current thinking on living systems is overly complex….Buy a copy…and see if, as suggested by one of the cover reviewers, it becomes you “scientific bible.” Milton Wainwright, Microbiology Today, 2001 One of the nice features of this book is that it starts with basic information so that readers without proper background can easily follow the development of the story. For the subject as diverse as this one ranging from biology (e.g., cell division, muscle contraction, and cell secretion) to polymer chemistry (e.g., diffusion through polymer network and phase transition), the book is incredibly easy to read. This is a science book that is as interesting as any non-fiction book listed in the best-seller list in the New York Times. At last, we have a book that clearly shows that the science book does not have to be boring. The author did an outstanding job in introducing a new theory, new insights, and a new way of thinking by combining biology with known polymer principles, in a way that almost anyone can afford. Kinam Park, Pharm. Research 18:1804-1805 This is no ordinary book. And it is not really a reference book. Its title gives very little away and may even be sufficiently meaningless as to fail to excite the interest of the passing eye. However, the sub-title shouts out its message quietly and confidently: “A new, unifying approach to cell function.” This book is a crusade! It is the nature of scientific progress that historical findings are built upon and extended by contemporary researchers. There is simply no time in the publication-driven production line of academic research to revisit and question the basis of work already done. The peer-review process, despite its recently exposed shortcomings, continues to provide warmth and comfort for groups of like-minded individuals working in broadly the same field and feeding from the same trough that is their source of research funding. It simply would not be right for any such individuals to question the underlying science in their field because that would be a guaranteed way of causing their flow of research funding to dry up. But Gerald Pollack dares to go where few would care to lead and questions long-established scientific tenets. What he has written will make uncomfortable reading for some. And being of thoroughly cynical disposition, I fear that those individuals who really should read this book will find several reasons why they shouldn’t bother. Gerald Pollack has drawn attention to experimental observations made many, many years ago that simply do not fit with current understanding of some rather important concepts as promulgated by basic undergraduate text books, university lecturers who use these books because they can often get free copies for evaluation, and of course those who go on to undertake research in these areas. Take for example, the sodium pump. To be fair, Gerald Pollack is only the messenger as far as what he has written about the sodium pump is concerned. He actually tells a story that was originally written by Gilbert Ling. I had to obtain a copy of one of Gilbert Ling’s recent publications (Physiol. Chem. Phys. & Med. NMR 29: 123-198, 1997) to gain a glimpse of the turmoil that has existed in the sodium pump field for about 50 years! Gilbert Ling carried out some simple experiments (simple in terms of what he was trying to observe: complex in terms of experimental design) as part of his Ph.D work. His observations did not fit with the then current understanding of the sodium pump. He writes that he was quietly advised that the sodium pump was a ‘Holy Cow’ and that he should stay away from it. He didn’t. His research funding dried up. His research students fled for fear of becoming unemployable. A smear campaign was instigated to blacken his name. But his results are clear: if you poison frog sartorius muscle with sodium iodoacetate, and/or provide a nitrogen atmosphere and/or cool the muscle preparations down to 0°C, ATP production should cease and the sodium pump should stop working. This should result in intracellular sodium levels rising as the sodium pump fails. But that is not what happens. If you want to see how Gerald Pollack tells the story, get his book. Suffice it to say that the sodium pump may well use ATP to do something that results in the movement of sodium and potassium ions in opposite directions across membranes, but that something has little if anything to do with maintaining potassium at high level and sodium at low level intracellularly. You don’t need a sodium pump to achieve this end because it happens spontaneously! If you are troubled by this observation, you should get Gerald Pollack’s book. But there is much more to Gerald Pollack’s book than a wish to revisit the sodium pump and to focus, for a change, on the water in living systems rather than on the proteins, carbohydrates, phospholipids, salts, etc. He develops a story that eloquently moves the reader towards a single unifying hypothesis built around phase transitions that occur in the structured water environment of living cells. The same phase transition phenomena can, it seems, provide mechanistic explanations for a multitude of intracellular events that are currently understood only in terms of the words that describe the observable phenomena. Consider, for example, what it is that you actually understand by the phrase ‘secretion of a neurotransmitter’. You could probably describe what is actually observed during this process, but could you explain mechanistically how secretion happens? Or how cell division happens? Or how muscle cells contract? Or how action potentials propagate (yes, I too have read the undergraduate textbooks, but the story about action potentials as it is commonly told, like the sodium pump story, contains rather significant omissions)? Or how transport of substances occurs through the gelatinous mass that is the intracellular environment (this is, I would submit, of fundamental significance to our understanding of intracellular therapeutic targeting of bioactive molecules)? Or how ATP works (yes, yes, I too have read the undergraduate textbooks and lectured on the subject)? Gerald Pollack attempts to do all of this and more. And I have to say that I find the case he makes compelling. Our understanding of the world is essentially just a story that is consistent with the currently available set of experimentally-derived data. New experimental data may either add colour or detail to the picture or they may expand the boundaries of the picture…but sometimes, and only very rarely, new data may require that the picture is erased and redrawn in a different way. If you have bothered to read this review to the end, you will probably also want to read Gerald Pollack’s book. I would commend it to you. We will then need to look for volunteers to rewrite the standard undergraduate biochemistry/cell biology textbooks. Gerald Pollack’s book is a monumental piece of work. Richard J. Schmidt, J. Pharmacy and Pharmacology 55: 857-858, 2003 The goals of this extremely readable and cleverly illustrated book are not modest. Gerald Pollack, professor of bioengineering at the University of Washington, begins by demeaning textbook renditions of cell biology as analogous to Ptolemaic epicycles. These renditions, he claims, are pedantic minutiae to be overthrown by a Copernican revolution that will leave us with a "new, unifying approach to cell function," one unencumbered by the mass of molecular details usually trolled by biologists in search of mechanisms. Cells, Gels and the Engines of Life is an eloquent and accessible statement of a heresy that has smoldered at the fringe of orthodox biology for about 30 years. Having often watched eyes glaze over as I try to preach that cytoskeletal polymer phase transitions are important for cell motility, I was ready to embrace a work that unabashedly and eloquently celebrates cells as polymer gels, without resorting to a single mathematical equation. Too little imagination, I have thought, has been applied to thinking through possible ways that biological gels (such as fibrin, collagen, elastin, and actin) influence human physiology and disease. Though Pollack's interpretations challenge conventional wisdom, such challenges should always be welcome. Thomas Stossel, Science 293 (5530), 611, 2001 This is a fascinating and extraordinary book. It challenges many of the concepts that have been accepted in contemporary cell biology. Yet it is written in an easy to read style that compels the reader to continue on. Pollack does not discount the earlier texts but acknowledges that his ideas add an extra dimension to some of the classical descriptions of cellular activities. A difference between this volume and the more classical texts is that Pollack offers explanations for how cell processes could work, whereas the classical texts describe the components involved but do not offer real explanations as to how things happen. As I read this book, I found myself rethinking some of our own work and wondering if structured water could be affecting the molecular interactions that we study in my lab. If a book prompts the reader to re-examine their thinking then it must be regarded as a success. I believe this book should be included in senior undergraduate, or postgraduate cell biology classes alongside the classical texts. This book may not be correct in all its details but as a focus for discussion and for the exploration of fresh ideas, it is a powerhouse. Dierdre Coombe, Immunology and Cell Biology 80, 506, 2002. Professor Gerald Pollack….challenges the fundamental concepts of modern cell biology. His latest publication “Cells, Gels and the Engines of Life: A New, Unifying Approach to Cell function” sends its readers a strong message that modern cell biology has been built on no stable bases, and that most of our knowledge about the cell may be completely wrong… This book is the collection of truths he has reached by starting biology himself with a clean slate; in a sense, it is his alterego. I read the draft of it for the first time a few years ago. Once I started reading it, it captured and has never released my mind. Since then, my attitude toward science has drastically changed. Although we have to honor the great accomplishments by the pioneers in the history of biology, this book taught me that it is necessary to reconsider them over and over again myself, too, from a non-biased standpoint. “Cells, Gels, and the Engines of Life: A New, Unifying Approach to Cell Function” is a must-have item. Its readers seeking the truth will soon find that it illuminates the darkness all around and opens the path leading to the highest peak of genuine biology. Hirohisa Tamagawa, Biochem Eng. Journal. 10: 155 2002 Capsule comments from distinguished professionals worldwide…. “I’m over the moon about this book. Once started, I knew I had to finish the unfolding story of new cellular players and cellular actions. Every cell biology curriculum should include this fresh and invigorating outlook.” --John Watterson, Lecturer Emeritus, Griffith University, Gold Coast, Australia “I have never read such impressive work since I entered the university 11 years ago. It will become my scientific bible.” --Hirohisa Tamagawa, Research Associate, Gifu University, Japan “In pleasant, readable style, Pollack opens a door towards third millennium biology. He asks penetrating questions that are not born out of his imagination but from careful analysis of puzzling results obtained by many investigators that do not fit current paradigms.” --Pascale Mentré, Maître de Conf., Pierre and Marie Curie University, Paris “I’ve carried this book around for some time and finally pulled it out on a recent flight, and literally couldn’t put it down. It is very good.” --Joseph Andrade, Professor and former Dean of Engineering, University of Utah “If the thesis advanced here is proven to be sound, there will be a revolution in cell biology. This book offers a dramatic alternative to the “conventional wisdom” of contemporary cell biology. Some of the material is deeply embedded in controversy, and although I did not always agree with the details, the overall message comes across clearly in this stimulating and enjoyable book. Pollack writes in a pleasant, often humorous style. If you wish to explore the spirit of qualified scientific dissent, this book is for you.” --James Clegg, Professor of Molecular and Cell Biology, University of California, Davis “Cells, Gels and the Engines of Life shows the power of treating the cell as it really is—a gel. With this approach, Pollack creates a fresh and compelling new foundation for cell biology. Anyone interested in discovering nature’s secrets will be forced by his/her curiosity to read this book. Once I started, I could not stop reading.” --Yoshi Osada, Professor and Director, Soft- and Wet-ware Laboratory, Hokkaido University, Japan “This is a great read. A very engaging discussion that constantly hits on things I (and probably most people in the field) have wondered about, and challenges the reader to rethink matters that are often taken for granted.” --Paul Janmey, Professor of Physiology, University of Pennsylvania “A most important book. Impressive and convincing for anyone who is open minded.” --Frank Mayer, Head, Structural Biology Department, Georg-August-University-Göttingen, Germany “Cells and Gels reads like a detective story. I could not stop reading until the plot resolved.” --Hiromasa Ishiwatari, Dean, Graduate School Health Sciences, Suzuka University, Japan “I read the book in one shot. It exposes the beauty of a critical tension between two poles of perception, and the intellectual pleasure of pursuing creative resolution. -Reuven Tirosh, Chief Scientist, Schottenstein Center, Bar Ilan University, Israel.