Cells, Gels, and the Engines of Life

My introduction to cellular biology was accompanied by a schematic drawing of a generic mammalian cell, a diagram that has been reproduced thousands of times in textbooks and journals. The colors vary, but the idea remains the same: The cell appears like a tiny balloon, with a pink nucleus, red mitochondria, blue Golgi, and so on, all surrounded by a thin line labeled ‘cellular membrane’. The cell’s key players float in a pale yellow sea called the ‘cytoplasm’, and beyond filing this word away for possible exam-day use, I had never really paid much attention to the seemingly innocuous solution in which the cellular drama unfolds. Of course, I later learned about cellular signaling, ion partitioning and pumping, and intracellular trafficking, but in each case, the cytoplasm itself stayed in the background. This was a naive oversight, and one that has been resoundingly remedied by a recent publication by Dr. Gerald H Pollack, grandly entitled ‘Cells, Gels, and the Engines of Life’. In this book, Dr. Pollack argues that the structured state of cytoplasmic water is of central importance to a huge array of cellular processes, from ion pumping (a term whose intrinsic meaning Pollack challenges) to essential cellular structure and motility. As this introduction should make clear, I’m not sufficiently expert on this topic to offer an informed critique of Pollack’s hypothesis. However, I also have no prejudice, and I belong to the book’s apparent target audience: generally well-informed biologists schooled in the traditional dogma of cell function. The book itself, comprising five major sections subdivided into 16 chapters, does an excellent job of walking the fine line between ‘boring’ hardcore scientific tome and ‘insubstantial’ pop-science rag. It is a beautifully produced volume full of color pictures, whimsical, cartoonish illustrations, and fanciful pictures (a car shaped like a stiletto high-heeled shoe opens a chapter called ‘transportation with flare’), and Pollack keeps the tone light and readable throughout. Casual readers thus placated, Pollack also gives a nod to his more critical readership with a 14-page reference section and plentiful allusions to ‘further readings’ on all major topics addressed. The first section, headed ‘Toward Ground Truth’, is an eye opener indeed. In the initial pages, the author compares the current state of cell biology with that of pre-Galilean astronomy, in which increasingly complex models of planetary motion were required to explain the mistaken hypothesis of an earth-centered solar system. This leads briskly into a challenge of the function of membrane-based ion pumps and channels; while the author concedes that proteins with pumpand channel-like properties do exist, he argues that the evidence that these proteins are actually responsible for observed cellular ion partitioning is sketchy at best. Pollack complains that the current models are based on a series of unfounded assumptions made to explain the phenomenon of ion partitioning. For example, intracellular sodium concentration is low, despite the fact that sodium can pass through the cell membrane; a pump was hypothesized to rid the cell of sodium, and the hypothesis stuck. The well-known patchclamp technique, a long-held gold standard for the pumpsand-channels model, is also criticized, in that silicon rubber, a polyethylene terephthalate filter, and a pure lipid bilayer all yield the distinctive current pattern thought to indicate the presence of an ion channel. The existence of ‘proteins exhibiting pump-like or channel-like behavior’ is justified by possible signaling roles. Storming ahead, Pollack next challenges the current thinking that the cell membrane is a continuous barrier that keeps small molecules in or out of the cell. This challenge is buttressed by the observation that ripping substantial holes in the cell membrane, and even cutting cells in half, does not cause the contents of the cell to gush out, deflating the victim like a ruptured beach ball; instead, cells can survive such assaults with little consequence. Finally, the nature of the cytoplasm itself is considered: cytoplasmic water freezes at lower temperatures than pure water, and ions do not diffuse as readily in the cytoplasm as in a beaker, leading to the enigmatic and ominous conclusion that ‘the cytoplasm is not the aqueous solution it is cracked up to be’. The first section ends leaving a significant gap in current theories of cell function: the idea of the cell as a membrane-bounded entity with pumps and channels that regulate the chemical makeup of its aqueous cytoplasm is called into question. To Dr. Pollack’s credit, he ends the chapter with a ‘perspective’, which urges the reader to reflect on the obviously unconventional message presented thus far, and refers to standard texts on conventional cell function to help skeptics make an informed decision regarding the central message of his hypothesis. The second section of the book, entitled ‘Building from Basics’, begins filling the holes in current cellular theory Cell Death and Differentiation (2003) 10, 266–268 & 2003 Nature Publishing Group All rights reserved 1350-9047/03 $25.00