A Computer in Every Living Cell Dennis Bray

A Computer in Every Living Cell Dennis Bray Yale University Press New Haven & London A goal for the future would be to determine the extent of knowledge the cell has of itself and how it utilizes this knowledge in a "thoughtful" manner when challenged. -BARBARA McCLINTOCK, Nobel Prize acceptance lecture, 1983 Contents Preface IX ONE Clever Cells TWO Simulated Life 27 THREE Protein Switches 54 FOUR Protein Signals 71 FIVE Cell Wiring 89 SIX Neural Nets 109 SEVEN Cell Awareness 1,'32 EIGHT Molecular Morphing 144 NINE Cells Together 167 TEN Genetic Circuits 179 ELEVEN Robots 195 TWELVE Thejuice 209 THIRTEEN Amoeba Redux 226 Glossary 243 Sources and Further Reading 251 Index 259 Preface in writing this book of being misunderstood. One of I received, after sending the manuscript to a large house, asserted that it was about single-celled organisms consciousness. Not true! I say repeatedly in the book as nglish words will allow that in my opinion single cells are not ware in the same way that we are. To me, consciousness fW•••igent awareness of self and the ability to experience intro spectively accessible mental states. No single-celled organism or indi vidual cell from a plant or animal has these properties. An individual cell, in my view, is a system that possesses the basic ingredients of life but lacks sentience. It is a robot made of biological materials. It cannot be denied, however, that those systems that do possess consciousness-principally human beings-are themselves made of cells. A very large number of cells, it is true, and linked in highly complex ways, but cells for all that. Moreover, there is a direct link in evolution and development between a single cell and humans. Cells are undeni ably the "stuff" from which consciousness is made. Some say that organization is paramount. If we were able to replace each nerve cell in our brain with an equivalent silicon device, they claim, then the outcome would be an entity with all the mental states of the original. The idea that computers of the future will be sentient and experience internal mental states is the starting point of many science fiction stories, part of the zeitgeist. But this is a theory without evi dence. We do not know it to be true. My own view, as you will see, is that present-day electronic devices and robots are woefully inadequate IX X PREFACE in this regard. They lack the multiplicity of states and plasticity dis played by living systems; they are unable to construct and repair them selves. Living cells have an unlimited capacity to detect and respond to their surroundings. An unending kaleidoscope of environmental challenges has been present throughout evolution. Organisms have responded by changing their chemistry; any that failed to adjust became extinct. And the richest source of variation was in the giant molecules that distin guish living systems. From a time-compressed view, the sequences and structures of RNA, DNA, and proteins can be thought of as continually morphing in response to the fluctuating world around them. These changes are cumulative with each modification adding to those that have gone before. It is as though each organism builds an image of the world-a description expressed not in words or in pixels but in the lan guage of chemistry. Every cell in your body carries with it an abstrac tion of its local surroundings in constellations of atoms. A basic knowledge of and response to the environment are integral parts of every living cell's makeup. The term wetware is not new, but I think it has not been closely de fined before. Wetware, in this book, is the sum of all the information rich molecular processes inside a living cell. It has resonance with the rigid hardware of electronic devices and the symbolic software that en codes memories and operating instructions, but is distinct from both of these. Cells are built of molecules that interact in complex webs, or cir cuits. These circuits perform logical operations that are analogous in many ways to electronic devices but have unique properties. The com putational units of life-the transistors, if you will-are its giant mole cules, especially proteins. Acting like miniature switches, they guide the biochemical processes of a cell this way or that. Linked into huge net works they form the basis of all of the distinctive properties of living systems. Molecular computations underlie the sophisticated decision making of single-cell organisms such as bacteria and amoebae. Protein complexes associated with DNA act like microchips to switch genes on and off in different cells-executing "programs" of development. Ma chines made of protein molecules are the basis for the contractions of PREFACE XI our muscles and the excitable, memory-encoding plasticity of the hu man brain. They are the seed corn of our awareness and sense of self. When a friend asked me who this hook was for, I ingenuously an swered, "Myself." Over the years I had acquired a ragbag of unanswered questions relating to living systems, computers, and consciousness and it was time to think them through and put them into order. So I did indeed set out, as John Steinbeck says in his Travels with Charley, "not to in struct others but to inform myself." But the discipline of writing calls for a voice and demands an imaginary reader. As I worked I found myself laying out my arguments as clearly as possible to someone lacking spe cialized background in biology or computers. My imaginary reader has a high school or equivalent background in basic science and a philosophi cal inclination. Ideally, she is already interested in such things as the comparison of living systems and computers and the origins of sentient properties from inanimate matter. The central thesis of the book-that living cells perform computations-arises from contemporary findings in the biological sci ences, especially biochemistry and molecular biology. It is a leitmotif of systems biology, although the philosophical ramifications of that new discipline are rarely expressed. Many readers with direct experience of computer-based games and virtual environments will also have wondered about their relationship to the world of real organisms. I hope that they will find here an elaboration if not an answer to their questions. This book took shape over many years and owes much to friends and colleagues. Hamid Bolouri and Armand Leroi saw an early version, and I am grateful for their positive response despite obvious flaws. Graeme Mitchison read the manuscript from beginning to end, and his com ments took the hook to a higher level. At a later stage, Horace Barlow made crucial improvements to the text as well as adding his considerable insight into the way the brain works. Aldo Faisal, Steve Grand, Frank Harold, Dan Heaton, Auke Ijspeert, Lizzie Jeffries, Dale Purves, Hugh Robinson, John Scholes, Yuhai Tu, Rob White, Be Wieringa, and Alan Winfield each helped me in difficult areas and made valuable sugges- Xll PREFACE tions. Claire Stroml super editorl went through the text like a butcher with a cleaverl flensing away the pompous verbiage we scientists are so fond of. Her daughterl Phoebel age fifteenl used a lighter touch to iden tify missing explanations ("Sometimes I think I get this and then it goes Poof!ll). Literary agent Peter Tallack and Yale editor Jean Thomson Black combined professional criticism with a genuine enthusiasm for the project that carried me along. Thank you all. 0 N E Clever Cells rainy November Cambridge afternoon when Bill Grimstone ared at my office in the Zoology Department and said he had thing to show me. It was rare, even during the term, to sight him, ost unusual for him to be in such an animated state. Bill was an typal imperturbable Cambridge don: suave, phlegmatic, with hair, spectacles and a slight cast in one eye, and given to wear 'w.... eed jacket and a tie. As I followed him down the corridor to his room, I speculated that there could be only one reason for this excitement-his research. Sure enough, as he ushered me into his small office, he gestured toward a wooden chair in front of a micro scope. Even before he flicked the switch to activate the light, I knew I would be looking at termite guts. Termites live by eating and digesting wood. In the tropics they build huge colonies like pillars, and, I gather, they can be serious pests if they settle into your home. I've also learned that termites, to gain nourishment from wood, have to degrade wood's primary component, cellulose, and that this requirement presents a biochemical challenge. Cellulose is just a chain of glucose subunits. But animals cannot digest this potentially rich source of food, for reasons that have always been a mystery to me. You might have thought that an evolving organism would easily acquire the single enzyme (a protein performing a specific reac tion) needed to tap into such a potentially rich source of energy. But the fact is that any animal, including an insect, that wants to digest wood 1 2 CLEVER CELLS must recruit bacteria. Termites do so by turning the gut into an oxygen free chamber full of special bacteria that degrade cellulose: a mutually beneficial menage because the termite provides the bacteria with a con stant supply of well-chewed wood fragments to digest. In return the bacteria turn the wood into sugars and other easily digestible molecules. They take some of the nutrients for their own use and leave the rest for their insect host.

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