The Equations of Life

by Charles S. Cockell

  In the blaze of the solar furnace, there is a balance to be had. The creature must use the sun to warm itself, but the loss of water threatens dehydration. It must evolve a thick impermeable skin that delays the loss of water. These innovations can be made good by changes in the genetic modules that control the development of skin cells. All these weird, new experiences now confront our nascent tetrapod as it seeks to navigate the nooks and crannies so unfamiliar against the predictable three-dimensional regularity of its former aquatic realm.

  Once a fuzzy blob in the aquatic void, the animal that now stares bemused at the star in the sky is bathed in UV rays, short wavelengths of light previously screened out by murky coastal water. It stares into the cold, uncompromising eyes of a relentless equation:

  E = hc/λ

  which describes the energy of light. This demon has become part of its world more than ever before. The energy of light (E), given by multiplying Planck’s constant (h) by the speed of light (c) and dividing by its wavelength (λ), determines that light with a smaller wavelength, such as UV radiation, has much more energy than does light of longer wavelengths. Those wavelengths now impart their energy to the surface of the fish, and with these rays comes the chance of radiation damage, familiar to you and me as sunburn, even cancer.

  The damaging effects of radiation are a strict physical rule. Shorter wavelengths of light have higher energy and can do more damage to molecules than can longer-wavelength light. This line of logic applies as much for our landlubber as it does for any other organism across the universe. In emerging onto land, where there is higher UV radiation, the animal might mutate to produce more pigment to protect itself. We do not know what the pigmentation of the earliest land dwellers looked like, but chemicals such as melanin might have been used. This pigment, found in our own skin, helps prevent radiation damage in life forms as diverse as fungi and animals. Its dark color causes suntans and the natural dark coloration of people who inhabit places where the rays of the sun are more unyielding, such as across Africa and Asia. Its chemical structure, a complex network of carbon rings and chains, probably evolved early on from the oversynthesis of an amino acid such as tyrosine, a pathway as ancient as the formation of proteins themselves. Even here, we find evidence of changes in existing genetic structures, the commandeering of old biochemical pathways for new roles and challenges in novel environments, but ones that are not so dramatically different that the laws of physics overwhelm.

  No matter where the UV-screening compounds came from or what their chemical structure or their color is, they are all driven in their evolution by the simple relationship that inheres in E = hc/λ. Not surprisingly, regardless of their origins, they all share some common attributes. Most have long chains or ring structures of carbon atoms that absorb in the UV radiation range, chemical structures mandated by the carbon bonds that most effectively absorb UV radiation, which are those with delocalized electron systems. Here we see evolutionary convergence at the chemical level, ultimately fashioned by the exposure of large animals to radiation in the environment.

  Clever adaptations to live on land did not have to be created from scratch. UV-screening compounds came from familiar biochemistry. Many marine organisms are exposed to some UV radiation. The clear open oceans allow UV radiation to penetrate far into the water, and except for the deepest-living ocean life, many marine organisms are exposed to some level of UV radiation. An assortment of the physical laws that operate on land exist also in the oceans; it is often just their magnitude or some components of the laws that are modified.

  Even problems that seem original may not be outlandish. Skin that prevents desiccation seems a distinctly terrestrial innovation, but of course fish do not want their innards diffusing into the sea. There is already a selection pressure for a robust barrier between the insides of fish and the outside world, a barrier that can be augmented in the dry environment of land.

  Once life had emerged onto land, its modular capacities to adapt continued to provide the promise for evolving in exciting ways. In experiments that tracked the expression of genes in python embryos, scientists at the University of Florida showed that the Hox genes to make limbs are still found in the DNA of these snakes. By naturally suppressing the production of a limb enhancer called Sonic hedgehog (SHH) (yes, biologists do have a strange sense of convention for naming genes), pythons prevent the limbs from forming. Through this rather elementary modification of gene expression, we move from four-legged animals to snakes and, with it, the ability to slither, unimpeded by limbs, through undergrowth, up into trees, and through sands and soils. The latent Hox genes may even explain the discovery of fossil snakes with limbs. Now long extinct, these ancient beasts probably regained their legs by merely reexpressing capacities that remain dormant in snakes to this day.

  Almost certainly, the secrets of that other extraordinary transition—from land back into water, a lifestyle change that needed limbs to be reformed into fins as the buoyancy term, ρVg, became a fact of life once more—are partly to be found in the Hox genes of whales.

  Evolutionary developmental biology has opened our eyes to how life can move from one environment to another, each containing a set of laws that in combination require modifications to the structure of life, achieved through a rearrangement of a few basic designs. They allow for the successful invasion of new habitats, all of which, though different in physical character, are still in gross form not too diverged from one another, sharing as they do the same gravity, atmosphere, and oceans that characterize our small world.

  Charles Darwin concluded his book On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life (it does the book an injustice not to quote its full Victorian melodramatic title) with this observation:

  There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.

  Here Darwin draws us to two important inferences. First is the overt notion that the Earth began with a law, the law of gravity, and then somehow broke away from this simple beginning into something more complex. The separation was not deliberate maybe, but a lasting legacy that implicitly separates physics from biology.

  His second statement, that from these simple beginnings “endless forms” emerged, is yet another implicit divergence from physics. This statement is easy to nitpick. Darwin was taken to literary flourishes every now and then; he was a good writer. And in some ways, Darwin was right. In detail, there are potentially endless forms. The possible arrangement of colors on a butterfly wing is probably limitless if we consider that every scale might have a different shade, hue, or color and be arranged in ever-so-slightly alternative tapestries. Like human faces, there is endless detail.

  But where he and I part is the general tenor of his conclusion. That the world emerged from something as banal and simple as the law of gravity and then exploded into an efflorescence of endless forms of biology is artistically captivating, but scientifically distracting. It is ironic that he picked gravity as his basic physical law, a law that plays an enormous role in shaping life at the large scale, from the scaling of animal sizes to the structure of trees. Gravity has indomitably followed the evolution of life from its very beginnings to the present day and made its unyielding mark on the form of things; it is a law that dominated the change in the character of life as creatures crawled from the sea to take ownership of the land; a law that has ensured that life on Earth is bounded and not endless.

  Physical rules continue to shape the form of living things, endless in detail, restricted in form.

  CHAPTER 5

  BUNDLES OF LIFE

  THERE ARE SOME NUMBERS so large we have no real way to comprehend them. If I tell you there are three poodles yapping outside my house in Bruntsfield, E
dinburgh, you can instantly envision those creatures, bubbly haired and boisterous, tottering and sniffing around on the cobbles. However, if I tell you there are about 3.7 trillion cells in your body, now the number is a just a fuzz, a number with no meaning. It is just gargantuan, so enormous that you cannot imagine this collection of objects.

  This is the realm we enter when we ask what living things are made of and from what units they are assembled. From the individual ladybugs, moles, and ants, we enter into the cellular dominion, the scale of life that is, as bricks are to a house, the next level down at which we find order in the makeup of life. At this level, too, we see that what was once a landscape of great complexity has given up its secrets to more easily understood physical principles. Through their manifestation in equations, the cellular world has become amenable to prediction, and the role of contingency has faded.

  We have no knowledge what Robert Hooke was expecting to see, if anything, when he took his microscope to some dried-up cork in the 1660s. Peering down the lens, he saw serried, or crowded, ranks of holes, rows and rows in regular formation, like little rooms in a monastery. Indeed, that was precisely the thought that struck him, for he called these minuscule compartments he saw before him cells, from the Latin word cella, or small room. Hooke had no inkling of the significance of these structures, and although he drew, alongside his famous fleas, diagrams of cells in his book Micrographia, published in 1665, no one else could see the significance of them, either.

  He was not alone in observing microscopic forms. Across the North Sea, another inquisitive scientist, Antonie van Leeuwenhoek, a Dutch tradesman, had fabricated pocket-sized microscopes made from glass beads. With this tool, he had sated his interest in this hidden universe by turning his new contraption to a multitude of things, from pond water to scrapings from his teeth. What he found in this previously unseen microcosm were creatures, “animalcules,” or animals in miniature, many of which seemed to move. He even observed how he could kill them: by exposing them to vinegar, he could arrest their movements. In a series of letters to the Royal Society, he documented his findings. As was the case with Hooke’s discoveries, it required creative thought to understand the significance of van Leeuwenhoek’s observations. To many, these dwarf living things were evidence of a miniature universe of animals for sure, but beyond that passing fancy and fascination, there was little more to be said.

  It would be another two centuries before the importance of this cellular cosmos was recognized—before the world would understand that those little holes seen by Hooke and the diminutive flitting animals documented by van Leeuwenhoek were the manifestation of the same phenomenon: tiny bundles of life, the unit of organization from which creatures are made. Hooke had seen the outlines of dried, empty shapes in his cork, but van Leeuwenhoek had seen independent living creatures. The Dutchman’s observations were of special significance since he had observed microbes, which through the work of Robert Koch, Louis Pasteur, and many others would turn out to be the harbingers of disease and the microscopic factories from which beer and wine spring forth.

  Observations of much more of the living world would bring this microscopic realm into front view. In 1839, Theodor Schwann and Matthias Jakob Schleiden, two German scientists, proposed the cell theory, an elegant idea that strung together several related observations that until then had remained disparate. Their idea, radical at the time, was that all living things comprise at least one cell or more; that cells are the fundamental unit of structure in all life and the source of all the varied functions in organisms; and that cells come from preexisting cells by some method of multiplication. Because the mechanisms behind all these conjectures were yet to be demonstrated, the theory was radical. Today, its tenets are so banal as to be obvious. We would recoil in describing these observations as the cell theory, but we would merely observe the fact that life is made from cells. The theory is just an accepted fact of biology, an observation that underpins the whole field of cell biology.

  With the benefit of another 150 years or so of research, we now know the principles that govern this most fundamental unit of life. We understand the physics and biology that run through it and where in this picture the contingent historical quirks of evolution could have their say.

  But first, we might ask why. What caused this strange packaging of life into bundles that enthralled Hooke, van Leeuwenhoek, and all those who followed them in this journey to a miniature world? One simple cause is the basic physical principle of dilution. Pour some bubble bath into a tub of water, and soon its color is all but extinguished as its molecules mix and disperse into the water. So too on early Earth, molecules would generally have been diluted into the oceans, rivers, and streams. These molecules would need very special locations, such as the inside of rocks, to be packed close enough to react with other molecules to build more-complex chemical machines. If those early replicators ended up inside a small container, then not only would they stay concentrated, but now the world would be their oyster. These cages of molecules could move out into otherwise more foreboding, diluting environments, like the oceans.

  The cell was, in simple terms, the answer to dilution, an innovation that allowed for expansion in a world with abundant water in which nature’s tendency is to dissipate. The universality of compartmentalization in this way is suggested as a defining feature of life and, with reproduction and evolution, the basis of all living things.

  Cells are certainly not the whole story of the biosphere. On Earth, we find biological entities without a cellular structure. Viruses, small pieces of infectious nucleic acids bound up in a protein coat, go about their business causing diseases such as the common cold in people and even causing mayhem in microbes. Yet these small hoodlums of the biosphere need a watery cell in which to propagate, a host in which to multiply. Because viruses are unable to reproduce on their own, without cellular life, some people question whether they should be allowed into the exclusive club of life or should be relegated to the less generous name of particles or entities. Prions, incorrectly folded proteins that propagate the errant folding of other proteins in a sort of chain reaction, leading to such grotesque infections as mad cow disease, are also thought by some to be outside the scope of life. Like viruses, they wreak their havoc in the cellular domain, but are not cellular themselves. Without cells, they are nothing, mere misfolded proteins in the wind. It seems inescapable that at least in our world, cellularity is a feature of life.

  We can easily comprehend the centrality of the cell in the phenomenon of life through a simple thought experiment. Imagine a hypothetical garden pond full of organic debris and material. Because of some strange weather, the material that blew into it, and some other factors, it develops metabolism. Raw materials get broken down to release energy. Even more amazingly, inside this pond, nucleic acids (DNA) evolve into a replicating system of information. Here, in someone’s inauspicious backyard, a prototype cell has come into being! Regardless of the potential of this garden pond, it is not going anywhere, trapped in its earthly burrow. There is no chance of replication or movement to new energy resources and nutrients. The “cell” is shackled.

  Our frustrated garden pond organism is a metaphor for any complex biochemistry confined to a physical space, whether that be a pore in a rock on the beach or an inscrutable hole in a hydrothermal vent. Any biochemistry that was randomly encapsulated within an early cell was released; it was set free to begin a planetary-scale expansion. It didn’t want to do this, but when this event occurred, replicating molecules were now likely to become abundant and exposed to many environments across the planet. These environments would act on the molecules to drive yet more variations and more life. Cellularity not only provided a concentrating mechanism, but also provided the means by which evolutionary selection in its myriad forms could occur. In that sense, cellularity and evolution are inextricably linked.

  An enticing question to ask is how the first cells might have come about. What formed that little cage in which m
olecules could congregate to make a self-replicating machine? Was it a particular contingent event in the history of life, a chance occurrence, or something more physically inevitable? To answer that question, we need to know something about how that capsule is formed and what it is made from.

  Look down at the edge of a cell and around each of them. In every self-replicating life form on the planet, you will find a membrane, essentially the bag that keeps everything in. This membrane is no mere sheet of boring bound-together chemicals, a sort of shopping bag in miniature. The molecules making up the membrane are dramatic in their character and beautiful in their simplicity.

  Within the membrane are molecules with a head and a tail, two distinct parts that are the secret of its clever chemical capabilities. The tail is a long chain of carbon atoms, one after another, in a string. These carbon atoms are hydrophobic, or insoluble in water. With no charge to make them soluble, just as oil does not mix with water, they will do all they can to avoid the substance. These tails are attached to the head, which has a different character. It is made with a charged group. In the phospholipids, an abundant class of these membrane molecules, the head is an atom of phosphorus bound to some oxygen atoms with a negative charge. The heads are hydrophilic; they like to dissolve in water So here we have a schizophrenic molecule, one end hydrophobic and one end hydrophilic. What is the molecule to do?