Table Of ContentA 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. ...e ed 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.
So as I looked down Bill's microscope I saw, as expected, ajum-
ble of wood fragments surrounded by the dark forms of bacteria,
rounded or rod-shaped. But as I fumbled with the unfamiliar controls,
something altogether more formidable slid into view. It was a single
cell, but as unlike the textbook fried-egg image of a cell as one could
imagine. This was a huge Wurlitzer of a cell, covered from head to foot
with writhing snakelike flagella-protrusions cells use to drive them
through water. Every portion of its body, which seemed immense un-
der the powerful magnification of the microscope, moved with its own
rhythm, as though driven by cogs and machines beneath the carapace.
As I passed the eyepiece to Bill, the writhing circular motion continued,
unfazed by our observation. "Trichonympha," Bill explained in his cul-
tured baritone. "And here," as he searched with the microscope stage,
"is Streblomastix, with a background of Spirochaetes." He had left the
microscope focused on a large serpentine body that bristled with sur-
face hairs surrounded by darting helical structures. As I watched, the
Streblomastix gave a sudden convulsive twist that carried it out of the
field of view.
We watched for perhaps twenty minutes until the preparation even-
tually died, probably through the seepage of poisonous oxygen. Bill de-
scribed and named one after another of the strange creatures we saw.
It was his research project, a.k.a. hobby, to classify and describe the in-
habitants of the dark recesses of the termite. Every now and then in the
past, he had selected a species with an especially intriguing anatomy for
further investigation. Fixed and embedded in resin, the creature would
be cut into ultrathin slices. Sections of its anatomy would be viewed in
an electron microscope-a procedure for which Bill was justifiably fa-
mous. Many of these pictures revealed new microanatomical structures,
