Bill Bryson - A short history of nearly everything

To this day it is not known how he got such magnificent magnifications from 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. [40]

Over a period of fifty years-beginning, remarkably enough, when he was already past forty-he made almost two hundred reports to the Royal Society, all written in Low Dutch, the only tongue of which he was master. Leeuwenhoek 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 mold, a bee’s stinger, blood cells, teeth, hair, his own saliva, excrement, and semen (these last with fretful apologies for their unsavory 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, Nicolaus 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.

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. Not until 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 preexisting cells. The belief became known as the “cell theory,” and it is the basis of all modern biology.

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 every where 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 is that it is all happening on a tiny scale: a mere 0.1 volts traveling distances measured in nanometers. However, scale that up and it would translate as a jolt of twenty million volts per meter, 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 pummeled 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.”

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 20,000 different types of protein, and of these about 2,000 types will each be represented by at least 50,000 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.”