What is Life?:How chemistry becomes biology (2 page)

The paradox inherent in the very existence of a living cell has profound consequences. It means that the issue of life’s emergence is not just some esoteric activity of historical interest, analogous to an individual seeking to uncover his family tree. Until the paradox associated with life’s emergence is resolved, we will not understand what life is. And, as final confirmation that understanding has been achieved, we will be able to translate that understanding into a coherent proposal for the synthesis of a chemical system that we would categorize as ‘living’.

The purpose of this book is to reassess this enthralling subject and demonstrate that a general law that underlies the emergence, existence, and nature of all living things can now be outlined. I will argue that thanks to a newly defined area of chemistry, termed by Günter von Kiedrowski ‘Systems Chemistry’, the existing chasm separating chemistry and biology can now be bridged, and that
the central biological paradigm, Darwinism, is just the biological manifestation of a broader physicochemical description of natural forces.
This admittedly ambitious attempt to merge biology into chemistry rests on the idea that there is a kind of stability in nature that has been previously overlooked, one I have termed
dynamic kinetic stability.
Amalgamating that form of stability into a Darwinian view of evolution leads to a
general (or extended) theory of evolution,
encompassing both biological
and
pre-biological systems. Interestingly, Darwin himself already understood that a general principle of life is likely to exist. In a letter to George Wallich in 1882 he wrote:

I believe that I have somewhere said (but cannot find the passage) that the principle of continuity renders it probable that the principle of life will hereafter be shown to be part, or consequence, of some general law …

This book is an attempt to demonstrate that Charles Darwin in his genius and far-sightedness was right, and that such a theory can now be formulated. I will attempt to show that chemistry, the science that bridges physics and biology, can provide answers, still in part incomplete, to these fascinating questions. Achieving a better understanding of what life is may not only tell us who and what we are, but will hopefully provide greater insight into the very nature of the cosmos and its most basic laws.

In writing this book, I have benefited from interaction with and input from many people. In particular I wish to thank Jan Engberts, Joel Harp, Sijbren Otto, and Leo Radom for detailed comments and criticisms of an early draft, to Mitchell Guss, Gerald Joyce, Elio Mattia, Elinor and David O’Neill, and Peter Strazewski for general comments, and to Gonen Ashkenasy, Stuart Kauffman, Günter von Kiedrowski, Ken Kraaijeveld, Puri Lopez-Garcia, Meir Lahav, Michael Meijler, Kepa Ruiz-Mirazo, Robert Pascal, Eörs Szathmáry, Emmanuel Tannenbaum, and Nathaniel Wagner for valuable discussions that have contributed to my understanding, and to Nella, my wife, for many discussions and for her critical eye and insights which have greatly impacted on the text. Finally I owe a very special debt to my Editor at OUP, Latha Menon. Her profound scientific understanding and remarkable editorial skills ensured the text did not stray unnecessarily into stormy biological waters and contributed greatly to its final form. Of course any errors that remain are purely my own.

Living and non-living entities are strikingly different, yet somehow the precise manner in which these two material forms relate to one another has remained provocatively out of reach. Life’s evident design, in particular, stands out, a source of endless speculation. The creativity and precision so evident in that design is nothing less than spectacular. The structural intricacy of the eye with its iris diaphragm, the lens with its variable focal length capability, the light-sensitive retina connected to the optic nerve for information transmission, is the classic example of nature’s design capability. But that’s just the very tip of the design iceberg. Due to the remarkable advances in molecular biology over the past six decades we have discovered that nature’s design capabilities can be immeasurably greater. Take the ribosome, for example. The ribosome is a tiny organelle present in all living cells in thousands of copies that manufactures the protein molecules on which all life is based. It effectively operates as a highly organized and intricate miniature factory, churning out those proteins—long chain-like
molecules—by stitching together a hundred or more amino acid molecules in just the right order, and all within a few seconds. And this exquisitely efficient entity is contained within a complex chemical structure that is just some 20–30 nanometres in diameter—that’s just 2–3 millionths of a centimetre! Think about that—an entire factory, with all the elements you’d expect to find in any regular factory, but within a structure so tiny it is completely invisible to the naked eye. Indeed, for elucidating the structure and function of this remarkable organelle, Ada Yonath from the Weizmann Institute, Israel, Venkatraman Ramakrishnan from the Laboratory of Molecular Biology at Cambridge, and Thomas Steitz from Yale University were awarded the 2009 Nobel Prize in Chemistry.

No less impressive than life’s extraordinary design capabilities is its breathtaking diversity, a perpetual source of inspiration. Red roses, giraffes, butterflies, snakes, towering redwoods, whales, fungi, crocodiles, cockroaches, mosquitoes, coral reefs—the mind boggles at nature’s spectacular and unmitigated creativity. Literally millions of species, and that’s before we have even touched upon the hidden kingdom, the bacterial one. That invisible kingdom is itself a source of overwhelming, almost incomprehensible diversity, one that is just beginning to come to light. But life’s design and diversity are just two characteristics out of a wider set that serve to compound the mystery and uniqueness of the life phenomenon. Some of life’s characteristics are so striking you don’t have to be too observant to notice them. Take life’s independent and purposeful character, for example. You can’t miss it. My granddaughter certainly didn’t, even when she was just 2 years old. She clearly appreciated the distinction between a real dog and a realistically
looking toy one. She happily played with toy ones, but was afraid of real ones, not being quite sure what surprise a real one might have in store for her. She learnt very quickly that a toy dog’s behaviour was predictable, while a real one had a mind of its own.

But there are other characteristics of life that are less obvious at first sight, though very obvious to the scientist in the lab, which also continue to tantalize and are in need of explanation. So if we want to understand what life is, where better to begin our journey of discovery than by considering the characteristics that distinguish living things from non-living ones. Ultimately, understanding life will require us to understand those special properties, both in themselves and how they came about. Some, as we will see, may be understood in Darwinian terms, though the debate about those explanations continues. Others, however, cannot be understood that way, and their very essence continues to trouble us. They certainly troubled the great physicists of the twentieth century, amongst them Bohr, Schrödinger, and Wigner, since several of life’s characteristics appear to undermine the most basic tenets of modern science. Yet other characteristics have led some modern biologists to throw up their arms in despair. How else to interpret the recent description of life by Carl Woese: ‘Organisms are resilient patterns in a turbulent flow—patterns in an energy flow.’
¹
That obscure remark, verging on the mystical, comes from one of the leading molecular biologists of the twentieth century—the discoverer of the Archaea, the third kingdom of life. Woese’s statement reaffirms how problematic the life issue continues to be.

So we have here an intriguing phenomenon—biologists, the scientists who devote themselves to the study of living systems, and who possess a deep appreciation of life’s complexity, having
successfully probed many of its key components, remain mystified by what life is, and physicists, with their deep understanding of nature’s most fundamental laws, are no less confused. Both continue to struggle with the nature of life question and we can only conclude that the 3,000-year ‘what is life’ riddle remains that—a riddle. Let us then begin our journey of discovery by briefly considering each of the characteristics that makes life special, so different to inanimate matter, and discuss what makes those characteristics so strange, so very strange.

Living things are highly complex. In fact the very first line in Richard Dawkins classic text
The Blind Watchmaker
begins with the remark that we animals are the most complicated things in the universe.
²
That attention-grabbing line on its own is enough to drive home the realization that we animals must be something very special. But what is it about us living things that makes us so complicated, or, to use the more scientific word, so complex? And what does the term ‘complex’ actually mean? At the risk of sounding circular, one could say the term ‘complexity’ is itself complex, not readily defined, and attempts over the years to quantify the concept have not proven too successful, at least not within a biological context. Let us then focus on the crucial aspect of complexity as it pertains to bioslogy—the highly organized nature of living things.

In the non-living world it is easy to find examples of complexity. The shape of a boulder is certainly complex and in that case the complexity derives from its irregular shape. To describe its shape
with precision would require information—the more irregular the shape, the more information would be required. The physical location of each point on the boulder’s surface would need to be specified in some manner. The important point, however, is that we understand that the boulder’s irregularity, the source of its complexity, is
arbitrary.
It could have been any one of a zillion other irregular shapes and the boulder would still be a boulder. It is not the particular irregularity of that boulder that makes it a boulder. By contrast, in the living world complexity is not arbitrary, but highly specific. Even the slightest structural change to that organized complexity may have dramatic consequences. For example, even a single change in a human’s DNA sequence, one out of 3 billion units, may potentially lead to thousands of genetic diseases, such as sickle cell anaemia, cystic fibrosis, and Huntington’s disease. Small changes to life’s complex structure may well undermine the viability of that living system, and in extreme cases the living system may be living no longer.

What is quite extraordinary and hard to comprehend is that such organized complexity extends to entities as small as a bacterial cell, just one thousandth of a millimetre across. In many respects the bacterial cell operates like a highly sophisticated nano-scale factory, nano-scale meaning the factory components are of molecular size, that is, of the order of one millionth of a millimetre in length. That nano-factory involves a highly complex but integrated network of chemical reactions, which extract energy from the environment, storing it in a number of different chemical forms for use in the biosynthesis of essential cellular building blocks; the control and regulation of the cellular machinery to ensure proper function; the list goes on and on. The cell is not just a master chemist, but a
master physicist as well. That microscopic entity uses every mechanical trick in the tradesman’s book—pumps, rotors, motors, propellers, even scissors to snip here and there, all at nano-scale, to ensure cellular functions are carried out expeditiously, as required by the cell’s ‘purpose’.

But that undisputed complexity, so different to inanimate complexity, is puzzling and raises two immediate questions. How is the organized complexity of the cell maintained, and how did it come into being? Organized complexity and one of the most fundamental laws of the universe—the Second Law of Thermodynamics—are inherently adversarial. We won’t go into the Second Law in any detail at this stage, but a very simple (and limited) expression of the Second Law is the statement that organized systems spontaneously tend toward disorganization, toward disorder. Nature prefers chaos to order, so disorganization is the natural order. Take a pack of cards in some highly ordered sequence—say four aces, followed by four kings, then by four queens, and so on, down to four twos—shuffle the deck and the sequence invariably becomes disordered. You’ll almost certainly end up with some random sequence. The likelihood of some other highly ordered sequence being formed is very slight. That’s the Second Law in action. The state of my desk at any point in time is further proof, if it were needed. No matter how often I tidy my desk, it always seems to quickly revert to its preferred disorganized state. Within living systems, however, the highly organized state that is absolutely essential for viable biological function is somehow maintained with remarkable precision. There is even a biological term for the phenomenon whereby that organized state is maintained—
homeostasis,
from the Greek meaning ‘standing still’.

So how is the cell’s organized complexity maintained, if a central law of physics and chemistry is constantly operating to undermine it? The answer to this first question is relatively easy, at least within the context of the Second Law: the living cell is able to maintain its structural integrity and its organization through the continual utilization of energy, which is in fact part of the cell’s
modus operandi.
That’s why we have to eat regularly to survive—to furnish the body with the necessary energy to enable the body’s regulatory mechanisms to maintain life’s organized homeostatic state. That also explains how my desk gets to be tidy occasionally—I expend energy now and then to restore a semblance of order whenever my desk has become too disordered to be functional. So there is no thermodynamic contradiction in life’s organized high-energy state, just as there is no contradiction in a car being able to drive uphill in opposition to the Earth’s gravitational pull, or a refrigerator in maintaining a cool interior despite the constant flow of heat into that interior from the warmer exterior. Both the car driving uphill and the refrigerator with its cold interior can maintain their energetically unstable state through the continual utilization of energy. In the car’s case the burning of gasoline in the car’s engine is the energy source, while in the case of the refrigerator, the energy source is the electricity supply that operates the refrigerator’s compressor. In an analogous manner, energetically speaking, the body can maintain its highly organized state through the continual utilization of energy from some external source—the chemical energy inherent within the foods we eat, or, in the case of plants, the solar energy that is captured by the chlorophyll pigment found in all plants. No fundamental problem there.