by Bill Bryson
Most living cells seldom last more than a month or so, but there are some notable exceptions. Liver cells can survive for years, though the components within them may be renewed every few days. Brain cells last as long as you do. You are issued with a hundred billion or so at birth and that is all you are ever going to get. It has been estimated that you lose five hundred of them an hour, so if you have any serious thinking to do there really isn’t a moment to waste. The good news is that the individual components of your brain cells are constantly renewed so that, as with the liver cells, no part of them is actually likely to be more than about a month old. Indeed, it has been suggested that there isn’t a single bit of any of us—not so much as a stray molecule—that was part of us nine years ago. It may not feel like it, but at the cellular level we are all youngsters.
The first person to describe a cell was Robert Hooke, whom we last encountered squabbling with Isaac Newton over credit for the invention of the inverse square law. Hooke achieved many things in his sixty-eight years—he was both an accomplished theoretician and a dab hand at making ingenious and useful instruments—but nothing he did brought him greater admiration than his popular book Micrographia: or Some Physiological Descriptions of Minute Bodies Made by Magnifying Glasses, published in 1665. It revealed to an enchanted public a universe of the very small that was far more diverse, crowded and finely structured than anyone had ever come close to imagining.
Illustrations from Robert Hooke’s popular and influential Micrographia, many people’s first look at the world of the microscopic. (Credit 24.3)
Among the microscopic features first identified by Hooke were little chambers in plants that he called “cells” because they reminded him of monks’ cells. Hooke calculated that a one-inch square of cork would contain 1,259,712,000 of these tiny chambers—the first appearance of such a very large number anywhere in science. Microscopes by this time had been around for a generation or so, but what set Hooke’s apart were their technical supremacy. They achieved magnifications of thirty times, making them the last word in seventeenth-century optical technology.
So it came as something of a shock when just a decade later Hooke and the other members of London’s Royal Society began to receive drawings and reports from an unlettered linen draper in the Dutch city of Delft employing magnifications of up to 275 times. The draper’s name was Antoni van Leeuwenhoek. Though he had little formal education and no background in science, he was a perceptive and dedicated observer and a technical genius.
To this day it is not known how he got such magnificent magnifications from such simple handheld devices, which were little more than modest wooden dowels with a tiny bubble of glass embedded in them, far more like magnifying glasses than what most of us think of as microscopes, but really not much like either. Leeuwenhoek made a new instrument for every experiment he performed and was extremely secretive about his techniques, though he did sometimes offer tips to the British on how they might improve their resolutions.2
Left: Antoni van Leeuwenhoek, painted here by his friend Jan Vermeer, was a self-taught instrument maker. (Credit 24.4a) Right: His simple, paddle-shaped microscopes produced magnifications far beyond any achieved by men of greater learning and expertise. (Credit 24.4b)
Over a period of fifty years—beginning, remarkably enough, when he was already past forty—Leeuwenhoek made almost two hundred reports to the Royal Society, all written in Low Dutch, the only tongue of which he was master. He offered no interpretations, but simply the facts of what he had found, accompanied by exquisite drawings. He sent reports on almost everything that could be usefully examined—bread mould, a bee’s stinger, blood cells, teeth, hair, his own saliva, excrement and semen (these last with fretful apologies for their inescapably unsavoury nature)—nearly all of which had never been seen microscopically before.
After he reported finding “animalcules” in a sample of pepper-water in 1676, the members of the Royal Society spent a year with the best devices English technology could produce searching for the “little animals” before finally getting the magnification right. What Leeuwenhoek had found were protozoa. He calculated that there were 8,280,000 of these tiny beings in a single drop of water—more than the number of people in Holland. The world teemed with life in ways and numbers that no-one had previously suspected.
Inspired by Leeuwenhoek’s fantastic findings, others began to peer into microscopes with such keenness that they sometimes found things that weren’t in fact there. One respected Dutch observer, Nicolaas Hartsoecker, was convinced he saw “tiny preformed men” in sperm cells. He called the little beings “homunculi,” and for some time many people believed that all humans—indeed, all creatures—were simply vastly inflated versions of tiny but complete precursor beings. Leeuwenhoek himself occasionally got carried away with his enthusiasms. In one of his least successful experiments he tried to study the explosive properties of gunpowder by observing a small blast at close range; he nearly blinded himself in the process.
An illustration by Nicolaas Hartsoecker of 1694 showing a homunculus. (Credit 24.5)
In 1683 Leeuwenhoek discovered bacteria—but that was about as far as progress could get for the next century and a half, because of the limitations of microscope technology. Not until 1831 would anyone first see the nucleus of a cell—it was found by the Scottish botanist Robert Brown, that frequent but always shadowy visitor to the history of science. Brown, who lived from 1773 to 1858, called it nucleus from the Latin nucula, meaning little nut or kernel. Only in 1839, however, did anyone realize that all living matter is cellular. It was Theodor Schwann, a German, who had this insight, and it was not only comparatively late, as scientific insights go, but not widely embraced at first. It wasn’t until the 1860s, and some landmark work by Louis Pasteur in France, that it was shown conclusively that life cannot arise spontaneously but must come from pre-existing cells. The belief became known as the “cell theory,” and it is the basis of all modern biology.
Microscopic specimens from an 1847 work by Theodor Schwann, the first person to realize that all living things are composed of and made from cells. (Credit 24.6)
The cell has been compared to many things, from “a complex chemical refinery” (by the physicist James Trefil) to “a vast, teeming metropolis” (the biochemist Guy Brown). A cell is both of those things and neither. It is like a refinery in that it is devoted to chemical activity on a grand scale and like a metropolis in that it is crowded and busy and filled with interactions that seem confused and random but clearly have some system to them. But it is a much more nightmarish place than any city or factory that you have ever seen. To begin with there is no up or down inside the cell (gravity doesn’t meaningfully apply at the cellular scale), and not an atom’s width of space is unused. There is activity everywhere and a ceaseless thrum of electrical energy. You may not feel terribly electrical, but you are. The food we eat and the oxygen we breathe are combined in the cells into electricity. The reason we don’t give each other massive shocks or scorch the sofa when we sit down is that it is all happening on a tiny scale: a mere 0.1 volts travelling distances measured in nanometres. However, scale that up and it would translate as a jolt of 20 million volts per metre, about the same as the charge carried by the main body of a thunderstorm.
Whatever their size or shape, nearly all your cells are built to fundamentally the same plan: they have an outer casing or membrane, a nucleus wherein resides the necessary genetic information to keep you going, and a busy space between the two called the cytoplasm. The membrane is not, as most of us imagine it, a durable, rubbery casing, something that you would need a sharp pin to prick. Rather, it is made up of a type of fatty material known as a lipid, which has the approximate consistency “of a light grade of machine oil,” to quote Sherwin B. Nuland. If that seems surprisingly insubstantial, bear in mind that at the microscopic level things behave differently. To anything on a molecular scale water becomes a kind of heavy-duty gel and a lipid is like iron.
If you could visit a cell, you wouldn’t like it. Blown up to a scale at which atoms were about the size of peas, a cell itself would be a sphere roughly half a mile across, and supported by a complex framework of girders called the cytoskeleton. Within it, millions upon millions of objects—some the size of basketballs, others the size of cars—would whiz about like bullets. There wouldn’t be a place you could stand without being pummelled and ripped thousands of times every second from every direction. Even for its full-time occupants the inside of a cell is a hazardous place. Each strand of DNA is on average attacked or damaged once every 8.4 seconds—ten thousand times in a day—by chemicals and other agents that whack into or carelessly slice through it, and each of these wounds must be swiftly stitched up if the cell is not to perish.
The proteins are especially lively, spinning, pulsating and flying into each other up to a billion times a second. Enzymes, themselves a type of protein, dash everywhere, performing up to a thousand tasks a second. Like greatly speeded-up worker ants, they busily build and rebuild molecules, hauling a piece off this one, adding a piece to that one. Some monitor passing proteins and mark with a chemical those that are irreparably damaged or flawed. Once so selected, the doomed proteins proceed to a structure called a proteasome, where they are stripped down and their components used to build new proteins. Some types of protein exist for less than half an hour; others survive for weeks. But all lead existences that are inconceivably frenzied. As de Duve notes, “the molecular world must necessarily remain entirely beyond the powers of our imagination owing to the incredible speed with which things happen in it.”
A stylized representation of the interior of a cell. The central object is the Golgi apparatus, which produces vesicles (shown as bluish spheres) for transporting enzymes and hormones. The air of spacious stateliness is a little misleading. Most cells are in fact packed and frenzied places. (Credit 24.7)
But slow things down, to a speed at which the interactions can be observed, and things don’t seem quite so unnerving. You can see that a cell is just millions of objects—lysosomes, endosomes, ribosomes, ligands, peroxisomes, proteins of every size and shape—bumping into millions of other objects and performing mundane tasks: extracting energy from nutrients, assembling structures, getting rid of waste, warding off intruders, sending and receiving messages, making repairs. Typically a cell will contain some twenty thousand different types of protein, and of these about two thousand types will each be represented by at least fifty thousand molecules. “This means,” says Nuland, “that even if we count only those molecules present in amounts of more than 50,000 each, the total is still a very minimum of 100 million protein molecules in each cell. Such a staggering figure gives some idea of the swarming immensity of biochemical activity within us.”
It is all an immensely demanding process. Your heart must pump 343 litres of blood an hour, over 8,000 litres every day, 3 million litres in a year—that’s enough to fill four Olympic-sized swimming pools—to keep all those cells freshly oxygenated. (And that’s at rest. During exercise the rate can increase as much as sixfold.) The oxygen is taken up by the mitochondria. These are the cells’ power stations and there are about a thousand of them in a typical cell, though the number varies considerably depending on what a cell does and how much energy it requires.
You may recall from an earlier chapter that the mitochondria are thought to have originated as captive bacteria and that they now live essentially as lodgers in our cells, preserving their own genetic instructions, dividing to their own timetable, speaking their own language. You may also recall that we are at the mercy of their goodwill. Here’s why. Virtually all the food and oxygen you take into your body are delivered, after processing, to the mitochondria, where they are converted into a molecule called adenosine triphosphate, or ATP.
A section of healthy heart muscle. The vertical pink bands (with darker horizontal stripes) contain filaments that are designed to slide over one another in response to electrical impulses, making the muscle contract. (Credit 24.8)
You may not have heard of ATP, but it is what keeps you going. ATP molecules are essentially little battery packs that move through the cell providing energy for all the cell’s processes, and you get through a lot of it. At any given moment, a typical cell in your body will have about one billion ATP molecules in it, and in two minutes every one of them will have been drained dry and another billion will have taken their place. Every day you produce and use up a volume of ATP equivalent to about half your body weight. Feel the warmth of your skin. That’s your ATP at work.
When cells are no longer needed, they die with what can only be called great dignity. They take down all the struts and buttresses that hold them together and quietly devour their component parts. The process is known as apoptosis or programmed cell death. Every day billions of your cells die for your benefit and billions of others clean up the mess. Cells can also die violently—for instance, when infected—but mostly they die because they are told to. Indeed, if not told to live—if not given some kind of active instruction from another cell—cells automatically kill themselves. Cells need a lot of reassurance.
When, as occasionally happens, a cell fails to expire in the prescribed manner, but rather begins to divide and proliferate wildly, we call the result cancer. Cancer cells are really just confused cells. Cells make this mistake fairly regularly, but the body has elaborate mechanisms for dealing with it. It is only very rarely that the process spirals out of control. On average, humans suffer one fatal malignancy for each 100 million billion cell divisions. Cancer is bad luck in every possible sense of the term.
Two highly magnified prostate cancer cells in the final stage of division. Cancers arise when cells fail to expire on cue. (Credit 24.9)
The wonder of cells is not that things occasionally go wrong, but that they manage everything so smoothly for decades at a stretch. They do so by constantly sending and monitoring streams of messages—a cacophony of messages—from all around the body: instructions, queries, corrections, requests for assistance, updates, notices to divide or expire. Most of these signals arrive by means of couriers called hormones, chemical entities such as insulin, adrenaline, oestrogen and testosterone that convey information from remote outposts like the thyroid and endocrine glands. Still other messages arrive by telegraph from the brain or from regional centres in a process called paracrine signalling. Finally, cells communicate directly with their neighbours to make sure their actions are co-ordinated.
What is perhaps most remarkable is that it is all just random frantic action, a sequence of endless encounters directed by nothing more than elemental rules of attraction and repulsion. There is clearly no thinking presence behind any of the actions of the cells. It all just happens, smoothly and repeatedly and so reliably that seldom are we even conscious of it; yet somehow all this produces not just order within the cell but a perfect harmony right across the organism. In ways that we have barely begun to understand, trillions upon trillions of reflexive chemical reactions add up to a mobile, thinking, decision-making you—or, come to that, a rather less reflective but still incredibly organized dung beetle. Every living thing, never forget, is a wonder of atomic engineering.
Indeed, some organisms that we think of as primitive enjoy a level of cellular organization that makes our own look carelessly pedestrian. Disassemble the cells of a sponge (by passing them through a sieve, for instance), then dump them into a solution and they will find their way back together and build themselves into a sponge again. You can do this to them over and over and they will doggedly reassemble because, like you and me and every other living thing, they have one overwhelming impulse: to continue to be.
And that’s because of a curious, determined, barely understood molecule that is itself not alive and for the most part doesn’t do anything at all. We call it DNA, and to begin to understand its supreme importance to science and to us we need to go back 160 years or so to Victorian England to the moment when the naturalist Ch
arles Darwin had what has been called “the single best idea that anyone has ever had”—and then, for reasons that take a little explaining, locked it away in a drawer for the next fifteen years.
Spicules, tiny interlocking structures made of calcium or silica, are the secret behind sponges’ remarkable ability to reassemble themselves when broken up. Because of their marvellously adaptable shapes, individual spicules can quickly reform to assume their former shape. (Credit 24.10)
1 Actually, quite a lot of cells are lost in the process of development, so the number you emerge with is really just a guess. Depending on which source you consult, it can vary by several orders of magnitude. The figure of 10 thousand trillion (or ten quadrillion) is from Margulis and Sagan, Microcosmos.
2 Leeuwenhoek was close friends with another Delft notable, the artist Jan Vermeer. In the mid-1600s Vermeer, who previously had been a competent but not outstanding artist, suddenly developed the mastery of light and perspective for which he has been celebrated ever since. Though it has never been proved, it has long been suspected that he used a camera obscura, a device for projecting images onto a flat surface through a lens. No such device was listed among Vermeer’s personal effects after his death, but it happens that the executor of Vermeer’s estate was none other than Antoni van Leeuwenhoek, the most secretive lens-maker of his day.
