The Top Designer

1.

We owe chemists and physicists our knowledge of the composition of living matter, of the conversion of the sun’s heat into chemical energy, and of the myriad molecular interactions that sustain life. Steven Vogel’s Cats’ Paws and Catapults is the first book that has made me look at biology through the eyes of an engineer and compare the mechanics of animals and plants with the objects produced by man. At first sight this project looks unpromising. How can you compare organisms that consist predominantly of carbon with machines that are made of metals? Many of nature’s engines are on the molecular scale, which means that they are about 100 million times smaller than a car engine. Man’s artifacts are deliberately designed, while nature’s structures have evolved blindly, haphazardly, over millions of years, by the reshuffling of genes, by mutation and natural selection of features that have led to more successful offspring. On the other hand, this very success requires living organisms to be constructed on sound engineering principles, which Vogel tries to explain.

He describes how nature has sometimes inspired man’s engineering designs. Otto Lilienthal, the German engineer, who was the first man to have lifted himself off the ground, modeled his gliders’ wings on a careful study of storks’ wings. The streamlined shapes of dolphins suggested the shapes of airplane bodies. Alexander Graham Bell, the inventor of the telephone, was not an electrical engineer, but a professor of vocal physiology at Boston University, where he taught deaf people how to speak. The anatomy of the ear led him to construct the first microphone. Our eardrums are thin membranes which transmit sound vibrations to tiny bones in the middle ear; those bones in turn set up vibrations in the liquid-filled canals of the inner ear which our auditory nerves sense by a mechanism still unknown. In Bell’s own words:

It occurred to me that if a membrane as thin as tissue paper could control the vibrations of bones that were, compared to it, of immense size and weight, why should not a larger and thicker membrane be able to vibrate a piece of iron in front of an electromagnet…and a simple piece of iron attached to a membrane be placed at the other end of the telegraphic circuit?

Bell replaced our eardrum by a thin metal plate which he attached to a magnetized iron rod surrounded by an independently fixed coil of copper wire. The metal plate transmitted sound vibrations to the iron rod, and its vibrations in turn induced vibrating electric currents in the copper coil. A wire transmitted these to a receiving coil which set up vibrations in an iron rod attached to a metal plate. This converted the electrical vibrations back into sound vibrations. So Bell made the analogy with the ear work both ways, as transmitter and receiver.

Figure 1

The ancient Egyptians made paper from papyrus; later, paper was made first from linen and then from cotton rags. In 1719, when the supply of rags threatened to fall behind demand, the French entomologist René-Antoine Réaumur noted that the American wasp (poliste) makes fine paper for its nests from wood, and he published an essay suggesting that this might be copied. In 1800 Réaumur’s article inspired one Matthias Koops in London to make paper from straw and wood. He incorporated this recipe in a book on the history of papermaking, but he went bankrupt after building a large mill, and it took a few more decades before wood paper became cheaper than rag paper.

Velcro, Vogel writes, is another example of man copying from nature. A Swiss engineer, Georges de Mestral, saw that the burs that clung to his socks and his dog after a walk in the hills had tiny hooks at the tips of their bristles, which he managed to reproduce in nylon felt. Such examples recall Descartes’s view:

The only difference I can see between machines and natural objects is that the workings of machines are mostly carried out by apparatus large enough to be readily perceptible to the senses (as is required to make their manual activity humanly possible), whereas natural processes almost always depend on parts so small that they virtually elude our senses.

Science has since sharpened our senses so that we can now see how these small parts are constructed and how they work. Nature’s engines are protein molecules, complex assemblies of thousands of atoms of carbon, oxygen, nitrogen, hydrogen, and sulphur; they are a thousand times smaller than the smallest object distinguishable in a light microscope, but electron microscopes make them visible, and another physical technique, X-ray crystallography, allows us to find the arrangement of the individual atoms inside them. These methods have shown that muscles contract by the interaction of two kinds of straight, long, rigid protein fibers

called myosin and actin. Myosin has extensions that resemble oars all around and along it. After each forward stroke, the oars hook on to the nearest actin fibers; at the backward stroke they propel the actin fiber relative to the myosin; so muscles work like long galleys propelled by oars all around them.

Figure 2

The power output of our muscles is weight for weight as good as that of electric motors and half as good as that of automobile engines, but aircraft turbines do thirty times better. In efficiency, muscles are comparable to gas turbines, piston engines, or electric motors. They all convert about 20 percent of the consumed energy into mechanical work. In all living organisms that energy comes from the universal biological fuel adenosine triphosphate, ATP for short, which is made by a remarkable engine described after Vogel had written his book.¹

In 1997 my colleague John Walker received the Nobel Prize for chemistry for unraveling the atomic structure and mechanism of that engine, which turned out to be a molecular turbine. A central protein shaft forms its axis; the shaft is surrounded by six protein molecules that catalyze the synthesis of ATP in three chemical steps.

Figure 3

The turbine spins at the rate of about 150 revolutions a second, churning out one molecule of ATP at each turn. It is driven by a protein dynamo which is fueled by the burning of sugars and whose structure has recently been elucidated by the research of Daniella Stock at the Medical Research Council Laboratory in Cambridge. As far as we know, the same engine is to be found in all living organisms from bacteria to man. It must therefore have arisen very early in evolution.

In the 1970s, biologists discovered that some bacteria also have turbines driving lashlike appendages called “flagella” that act as propellers.

Figure 4

Close to the turbines are sensors, molecular noses that smell food. In the absence of food the propellers idle, but when the sensors smell food, they drive the bacteria toward it. We still don’t understand how the turbines work or how they are switched on and off. They may be driven like the ones that drive the ATP factory.

Nature has evolved molecular turbines, but no wheels; nor did primitive societies have them, because wheels need roads. Cart wheels cannot go over bumps higher than a quarter of their diameter; they also sink in sand.

Vogel writes that the ancient Egyptians transported the stone blocks for their pyramids, each weighing 2.5 tons, by rolling them along on logs, and that there are Egyptian and Assyrian illustrations showing huge statues mounted on sleds being dragged along by large numbers of men. But the Australian-born Cambridge engineer R.H.G. Parry has found evidence that they used a more efficient method. The great pyramid of Cheops contains some 2.3 million limestone blocks weighing on average 2.5 tons; some weigh up to 6.7 tons. It is believed that the pyramid was built in only twenty years; Parry calculates that the stones would have to have been placed at an average rate of one every two minutes during all the daylight hours of that period. He argues that all methods hitherto proposed would have been too slow to account for the rapid transport of the stones from the distant quarries to the site, and it would have been too hazardous to lift them into position, especially the massive granite blocks of the King’s chamber.

Small wooden cradlelike objects found in the New Kingdom Foundation Deposits gave Parry the idea that these resembled the huge cradles used to envelop the large blocks of stone and so turn the cradled stones into wheels that could be rolled along the ground. One such cradle would have been fitted to each of the four sides of a stone block to form circular runners. Parry worked out that the sliding of a 2.5-ton stone along a flat surface would take about twenty-five men, while pushing it along on circular runners would take no more than two men, and that rolling it up the slope of the pyramid needed a force of only one quarter of that required to slide it up.

Figure 5

Such a method, Parry suggests, is more likely to have been used by a highly intelligent and sophisticated people than the primitive ones proposed earlier.

Nature makes no wheels, but it does make bearings which are as smooth as those of the best engines. At our hips, knees, and elbows, bones are covered with cartilage and form ball and socket joints; they are lubricated by synovial fluid which allows them to slide over each other with almost no friction.

Nature has also evolved molecular syringes. Just as small fleas proverbially are said to have even smaller fleas upon their backs to bite them, coli bacteria are bitten by viruses, which were discovered early in this century by the French physician F. d’Herelle, who called them bacteriophages (phage is Greek for “glutton”). D’Herelle’s phage consists of a protein cylinder that acts as a container for the long chain of DNA that carries the genes, about 250 of them, needed to specify this simplest of organisms. Attached to the cylinder is a tail with long fibers at its tip. The phage attaches itself to its victim with these fibers; the tail then contracts and injects the DNA into the bacterium. The DNA replicates itself, and its replicas direct the synthesis and assembly of more phage proteins. Twenty minutes later the dead bacterium bursts with the release of up to two hundred progeny phages.

Figure 6

Such phages are among the fastest-reproducing organisms we know of. D’Herelle hoped that his phages would become effective weapons against bacterial infections, but his hopes were disappointed.

Living creatures walk, run, jump, swim, or fly; much of Vogel’s book turns on the engineering principles of their motions. Muscle has little elasticity; once contracted, it does not reexpand unless stretched by another muscle or by an elastic element coupled to it, or by gravity. Vogel explains that

we cheapen our walking gait with a little gravitational, pendulum-like, storage [of energy] between strides. When we walk faster than the pace set by the period of our legs as pendulums, they are switched to jogging, for a middle-sized human at about five miles an hour.

Figure 7

When a creature runs or jumps, energy is stored in stretched tendons, which consist of protein chains; they stretch elastically by no more than 10 percent of their length, but that is enough to assist a kangaroo’s jump. On landing from one jump, its tendons are stretched and help lift it on to the next one. About 40 percent of the stored energy assists its lift and the rest is lost as heat. This seems wasteful, but most man-made engines waste more energy. Fleas store elastic energy by compressing an elastic pad made of a highly resilient protein. Release of the pressure launches them on a leap of several hundred times their own length. They may be the catapults referred to in the title of Vogel’s book.

The Russian physicist Peter Kapitsa set his students the examination question “How fast would Jesus have had to walk over the waves in order not to sink?” Using the soles of his feet as surfboards, he would have needed prodigious speed to make their small area provide enough lift for his weight. An aquatic bug weighing ten million times less can do it easily because water is covered by a skin of water molecules which stick to each other firmly enough to support it on its six wax-coated feet.

Marine animals and birds, penguins for example, swim under water rather than on it, surfacing in order to breathe. Vogel explains that the movement of an underwater swimmer is opposed only by the drag of the water adhering to its body; drag can be minimized by streamlining the body as in a whale or a dolphin. On the other hand, a surface swimmer’s movement is opposed also by the waves he generates. Their wavelength equals the length of his body, while their speed rises with the square root of the wavelength, doubling with a fourfold increase in length. When a swimmer or ship tries to go faster than its waves, it has either to cut through them or to go perpetually uphill. A ship a hundred feet long reaches that critical speed at about fifteen miles an hour, but for a duck it’s only one and a half miles an hour, twenty times slower than its speed in air. It can swim much faster under water.

The famous geneticist J.B.S. Haldane was a large, burly man with a small moustache. Educated at Eton and dressed in tweeds, he might have been taken for a pillar of the establishment, but he was an active member of the Communist Party and wrote a weekly science column for the Daily Worker. In 1927, Vogel recalls, he wrote “On Being the Right Size,” a playful essay on the ratio between an animal’s height and its weight. Gulliver’s giants of Brobdignag, who were a hundred feet tall, would have weighed 280 tons, or 4,600 times more than Gulliver, but since their bones would have been only three hundred times thicker they would have crumbled under their own weight. Gulliver’s Lilliputians, on the other hand, were only six inches tall. They would have profited from being able to fall a long way without hurting themselves, because the air’s drag would have slowed their fall more than that of a full-sized man. The drag that slows a falling object is proportional to its surface area. The ratio of a Lilliputian’s surface area to his weight would have been sixteen times greater than that of a full-sized man, and this would have slowed his fall. An even greater ratio of surface area to weight lets mice fall down mine shafts and run away unharmed.

Vogel points also to a handicap that would have afflicted Lilliputians, but had escaped Haldane’s notice: the heat lost by animals is also proportional to the ratio of their surface area to their weight, so that they would have lost heat sixteen times faster than Gulliver and might have frozen to death in cold weather. This is why babies have to be kept warm. The smallest warm-blooded animals, shrews and hummingbirds, have to eat almost continuously just to keep warm. To reduce their loss of heat during the night, they lower their body temperature as if they were hibernating.

Vogel extols the advantages of being curved. Bookshelves sag because they are flat, but sagging can be reduced by making them curved, as well as by beams or struts. Many kinds of leaves are stiffened by being just a little curved, but that makes them catch the wind, so that a gale can fell a tree. Vogel found a defense. To measure air drag on single leaves, he suspended them in a highly turbulent wind tunnel at speeds they might meet in a storm. As this storm caught the leaves from a maple or a tulip poplar, they coiled up into cones that minimized air drag.

Figure 8

Vogel’s chapter on the stress put on objects—through compression and tension—dwells on cathedrals and bridges, but says too little about the impressive construction of bones, including teeth. Gothic cathedrals were designed to resist compression: “Vaulted roofs press outward on the walls, and exterior buttresses press inward, with the two in very close balance.” On the other hand, Filippo Brunelleschi encircled the great dome of the cathedral of Santa Maria del Fiore in Florence with massive iron chains to balance the tension on its periphery. For material that resists both compression and tension, engineers use composites, like concrete reinforced with steel rods. In nature, wood is a composite of cellulose fibers and the glue lignin, and bones are composites of protein fibers made of collagen and a concretelike mineral, calcium phosphate. A rat’s incisor teeth are made up of that hard mineral arranged in layers of mutually perpendicular rods, like crossed beams in a ceiling, that give the teeth great strength and resistance to wear.

Photo

Vogel, I was disappointed to find, gives no statistics to compare the strength of wooden beams and iron girders, or of bones and steel tubes, or of tendons and nylon strings, matters that engineers must think about when designing artificial limbs.

Vogel mentions two kinds of levers: amplifiers of force used by humans and amplifiers of distance used in nature. Nutcrackers increase the force of one’s hand by having a long arm from the hand to its pivot, and a short one from the pivot to the nut, while insect wings are anchored so as to transmit force over a long distance from their pivots. Some insect wings are coupled to elastic elements whose vibrations make them swing up and down more than a thousand times per second. Vogel’s book is filled with many other examples of nature’s engineering designs. Its only continuous theme is nature’s ingenuity, which he demonstrates with unbounded enthusiasm and without any scientific jargon.

Maintenance of mechanical devices includes the replacement of parts. Replacements of hips and knees have now become routine, but most of us live with the organs and joints we were born with, because the cells that make them up are being replaced continuously by freshly synthesized ones. This is vital, because many of our proteins are unstable, i.e., they decompose into small compounds which may be either recycled or excreted. Then why are we not immortal? Partly because our maintenance system omits our hearts and brains; partly because that system is error-prone and the errors may accumulate with time. Our life span may also be genetically programmed by structures of DNA attached to the ends of our chromosomes and other devices yet unknown.

2.

François Jacob made his scientific name by discovering how genes are switched on and off in bacteria, and became known as a writer for his moving autobiography The Statue Within. In his latest book, Of Flies, Mice, and Men, he asks what decides whether a fertilized egg develops into a mouse, a fly, or a human. He writes:

What is…wonderful about the appearance of a new human being is not the nature of the receptacle in which the first stage takes place. It would not even be the accomplishment of making the entire development take place in a test tube. The incredible thing is the process itself. It is that the meeting of the sperm with the egg initiates a gigantic set of chemical reactions, hundreds of thousands of which follow each other, overlap and cross each other in an orderly network of unbelievable complexity. All this to result…in the appearance of a human baby and never a little duck, a little giraffe or a little butterfly.²

How can we penetrate that complexity and discover what decides the differences between the development of different species? The bodies of all organisms are made largely of proteins. Protein molecules form the machinery that makes them alive, and the blueprints for them reside in the genes, of which humans possess about 80,000. One might think that the differences among species would be reflected in differences among the structures of these proteins, but this is not so. The structures of protein molecules with similar functions in distantly related species are so closely alike that they could not possibly determine the macroscopic differences among these species. Some species contain proteins that others don’t have, and higher organisms have more genes than lower ones and therefore a greater variety of protein with different functions. Even so, the variety of species conceals an astonishing unity in the makeup of their molecules.

The first clue to the factors that determine the development of an organism came from studies of the geneticists’ pet, the humble fruit fly. There are flies that grow legs on their heads in the place where they should have antennae. The mutant gene responsible for this monstrosity lies on one of the fly’s chromosomes, and it belongs to a family of genes that determine the fly’s body plan. Are these genes unique to the fly, or do similar genes determine the development of a human embryo? The answer to that question has had to wait for the invention of recombinant DNA technology, which has made it possible to isolate, copy, and amplify genes from a fly and to introduce them into a mouse or vice versa. François Jacob describes a group of genes that determine the sequence of embryonic developments along an axis from the front to the rear of the fly’s larva. He writes:

There was hardly a chance of finding these genes in organisms other than insects, seeing how different their embryonic developments are. But people looked for them all the same. Just to see. They were stunned. They found them. Everywhere. First in a frog, then a mouse, then in man, in a leech, in a worm…. In short, one finds a group of genes very similar to those of the fly in all animals. Everywhere, their role seems to be the same: to define the identity of different cells along the axis from the front to the rear of the animal. If one takes a mutant fly which lacks one of these genes and inserts in its place the homologous gene from a mouse, it works, and it fulfils the same function as the normal fly gene.

Insect eyes differ fundamentally from animal eyes: the fly focuses light over a wide angle through hundreds of separate facets, while animals focus light over a narrower angle through a single lens. One would therefore have expected the development of their eyes to be controlled by different genes. To everyone’s astonishment this has proved untrue. Certain fruit flies fail to develop eyes, a defect that has been traced to mutations in either of only two genes. When geneticists added the homologous mouse gene to the fly, the fly developed an additional fly’s eye and not a mouse eye.

Figure 9

Similarly, a mouse which had its own gene controlling development of the eye replaced by the homologous fly gene developed a normal mouse eye. Some stillborn human babies have no eyes. Their defect was found to be due to mutations of the same genes that govern the growth of the flies’ eyes.

This discovery raises a question that vexed Charles Darwin. How could an organ as subtle and complex as the eye have arisen by evolution and natural selection, rather than been designed and brought into being by an omniscient creator? The biologist Ernst Meyr believed he had at least a partial answer when it seemed as though eyes had evolved independently in about forty different species; but if the same gene initiates the development of eyes in all species, then this suggests that they have all developed from a single light-sensitive cell which arose early in evolution.

This discovery has not answered Darwin’s question, but only deepened the mystery. If the development of eyes is initiated by the same gene in humans and flies, then why are they so different? The Swiss biologist Walter Gehring suggests that in human beings the single gene switches on a cascade of as many as 2,500 other genes. They would code for 2,500 different proteins whose complex interplay would then govern the growth of the eye. Some of these proteins might be common to human beings and flies and others different. We know as yet next to nothing about them.

Will we ever be able to unravel these genes’ labyrinthine workings? In the concluding chapter of his book, Jacob asks whether there are limits to scientific knowledge. For instance, research may slow down because it has become unmanageably elaborate and extensive, “like a building that cannot rise to infinite heights.” Or else there might be a limit to our understanding, which could be “like a net that can catch only fish larger than its holes, or a microscope that cannot resolve details smaller than the resolving power of its lenses.” There might indeed be a limit to the degree of complexity that we can comprehend, such as the interactions between thousands of genes or between the billions of neurons in our brains. Jacob fears that “the human brain may be incapable of understanding the human brain.” I share his fears.

Jacob’s thesis, repeated in this book, is that much of evolution has arisen from Nature’s tinkering. Just as mechanics put new cars together by tinkering with bits and pieces from several old ones, the processes of Nature make new genes which code for proteins with new functions by putting together bits and pieces from several existing genes in new ways, or simply by replacing bits and pieces in existing genes. How are these processes initiated in one case and not in another? Here Jacob writes:

The whole of the living world looks like some kind of giant Erector set. Pieces can be taken apart and put together again in different ways, to produce different forms. But fundamentally the same pieces are always retained.

For example, the “expression of genes”—i.e., their production of proteins—is switched on by proteins known as transcription factors. There is a specific combination of transcription factors for each gene. It combines with the gene on receipt of a specific signal, say a hormone like insulin. There are hundreds, if not thousands, of different transcription factors, all similarly constructed with just a few bits and pieces in different places to make them respond to different chemical signals and then combine with different genes.

New combinations of parental genes form the basis of inherited individuality. “Each of us,” Jacob writes, “is different from all other human beings who ever lived, now live, or will live on earth.” Unless people are mad enough to have themselves cloned.

Jacob has scathing criticisms of eugenic proposals to use “frozen sperm from carefully selected donors.” He writes that some people are even excited by the idea of fertilizing human eggs with the sperm of Nobel laureates (since they probably don’t know any Nobel laureates). But how should we select for complex traits directed by many genes about which we know nothing? Which genes are we to consider the best? Or which genes would we wish to eliminate? Each of us contains a mosaic of good and bad ones. Abraham Lincoln is thought to have suffered from an inherited bone disease, Dostoyevsky was an epileptic, Virginia Woolf a manic depressive. Had eugenics been used to eliminate human fetuses with deleterious genes, none of the three would have lived.

Knowledge of the human genome, and mapping of the genes that make us susceptible to a variety of diseases, will mean, Jacob predicts, that “people will become patients before their time. Their condition, their future will be discussed in medical terms, even though they feel fine and will remain in good health for years….” And “whether means of treatment exist or not, potential disorders will announce themselves in future as never before.” I would add that they will do so in rich societies that can afford to spend large sums on genetic screening—that is, among a small minority of mankind. The health of most people on earth is still threatened primarily by parasitic and infectious diseases and by malnutrition, whose conquest presents a greater challenge to medicine and society.

Part of Jacob’s book is about his life as a scientist and about science in general. “The history of science,”he writes, “is the history of the battle of reason against revealed truth” (in which I would include political ideologies such as Marxism). “Pandora introduced a fundamental ambiguity into the world. From now on every good would be twinned with its evil counterpart, every light with its shadows….”

Discussing these shadows, Jacob writes that “no one would have expected that the speed and growth” of medicine and public health since the end of the last century “would lead to overpopulation, which poses one of the greatest threats to humanity.” It now looks as though AIDS may become the greatest threat instead. It is well on the way to decimating India; in parts of Africa as many as 25 percent of the people are already affected, and eventually it may almost wipe out entire populations.

Like its predecessors, Jacob’s book is masterly in combining erudition, wit, and wisdom. It is marvelously clear in describing what we know about the fundamental questions of life and the laws that determine the growth of each species—and what we don’t know.