by Guy Murchie
Comparable careers of other deadly contagions include typhus, meningitis, anthrax, scarlet fever, yellow fever and, in their various ways, malaria, filariasis, cholera, tuberculosis, typhoid, influenza, diphtheria, measles, leprosy, gonorrhea, syphilis, rabies and many more - all being the collective names for colonial organisms recently discovered to have flourished at one time or another inside individual humans, but also recorded throughout history to have been imperialistic superorganisms exploring and competing irregularly about the surface of the planet, at once invisible and as big as the world. Like other organisms, they are kept by evolutionary forces in a perpetual state of change, now looming out of "nowhere," now vanishing like smoke, now aiding or hindering a fellow disease for no known reason, ever probing, adapting, competing, evolving. There is evidence, for instance, that leprosy was all but extinguished by the medieval waves of bubonic plague that swept through the huge leper colonies of Europe, a case of one disease eliminating another.
Man, however, may now be influencing diseases more than they influence each other, not only by conquering or controlling many such killers as bubonic plague, typhus, tuberculosis and polio, plus totally extinguishing smallpox (as he seems to have done), but roughly seventy-five percent of present human ills, especially in the wealthier countries, are attributable to man himself. Called the iatrogenic diseases, many of these have arisen directly out of man's adoption of artificial drugs (like embryonic deformity after a pregnant woman has taken thalidomide), some sprang up indirectly (like a new strain of bacteria that feeds on penicillin) and some (such as high blood pressure, heart disease, cancer and asthma) can be largely attributed to the adverse effects of new human habits and occupations.
Returning now to Leeuwenhoek, we can see that it was his epic discovery of the reality of microscopic hordes of living organisms that made possible the increasingly plausible germ hypotheses of the eighteenth century, outstanding among them the closely reasoned treatise on germ theory published in 1762 by Dr. Anton von Plenciz of Vienna. And then came the pragmatic discovery in 1796 by Edward Jenner, a country doctor of Gloucestershire, who, after hearing that milkmaids who'd had cowpox were immune to smallpox, made a few experiments and then publicly demonstrated that nearly anyone could be immunized against smallpox by rubbing matter from a cowpox pustule into an open scratch on his skin. Of course no one could explain why it usually worked and there were vociferous doubters and a good many cases of persons thus "vaccinated" (from vacca, cow) coming down with infections (not necessarily a pox) as a result of some unwitting contamination.
Half a century later the causal relation between a microbe (fungus) and a vegetable disease (potato blight) became pretty well established during the terrible Irish famine of the 1840s, but it remained for a young French chemistry professor named Louis Pasteur, who had done research in the physics of crystals, to prove the connection between microbes and human or animal disease. Studying the fermentation of beet juice leavened with yeast for an alcohol maker in Lille in 1857, he noticed a certain optical property in the fermented crystals that resembled what he remembered having seen in biologically grown crystals and this made him suspect yeast of being a live organism rather than just a chemical, as was the common assumption of the day. Testing the idea, he. soon realized that all of the various kinds of fermentation in milk, wine, bread, cheese, etc., might be caused by living organisms, perhaps different ones in each case, and that some of the invisible living creatures Leeuwenhoek had found floating around on dust could well cause diseases too. It was relatively easy to prove that a sterile liquid like freshly boiled bouillon would not ferment if kept free of dust-laden air but it took Pasteur (with the help of others) many years to work out the organic chemical processes by which bacteria convert milk sugar into the lactic acid of souring milk, by which yeast changes grape sugar into the alcohol of wine, by which certain bacteria turn wine into the acetic acid of vinegar, and so forth. Yet this he eventually did, mostly during the 1860s, and by his great work the germ theory - that invisible creatures are capable of conquering and killing men or even elephants while swimming through their blood - preposterous on the face of it, became generally accepted as fact. And the fantastic concept was further established by such perspicacious pioneers as the English surgeon Joseph Lister, who quickly and successfully applied it in his operating procedure by sterilizing open incisions with a spray of carbolic acid; a decade later by the young German medical researcher Robert Koch, who, having learned to photograph bacteria, identified the bacilli that cause anthrax, tuberculosis, cholera and others; followed by increasing numbers of other biologists with their growing lists of positively identified disease-carrying germs.
It was not until 1887, however, that anyone actually saw one of the ultramicroscopic microbes we now call viruses (which had been suspected by Pasteur and others). The Scottish surgeon Dr. John Buist, who beheld the barely visible reddish specks of cowpox virus (about 1/1000,000 inch long) in his microscope, supposed them to be "spores" of bacteria or fungi. But a decade later a gruff Dutch botany professor named Martinus Willem Beijerinck discovered that the juice of a diseased tobacco leaf, after being passed through a porcelain filter to eliminate all bacteria, would still infect healthy tobacco leaves and the mosaic-like infection could spread indefinitely. He could not see any microbes in it with his microscope, so he concluded that the agent of the disease must be a "filterable virus" too small to see and somehow living without any solid structure in the liquid. While his "liquid life" concept never was taken seriously by other biologists, a third of a century passed before an English medical researcher, Dr. Willis J. Elford, in 1931 obtained conclusive evidence (with ultrafilters which stopped viruses while letting liquids through) that viruses must be solid particles.
And then in 1935 a young American chemist, Wendell M. Stanley, succeeded in purifying a solution of tobacco mosaic virus (TMV to virologists) into the strange form of a white, sugary, crystalline powder that seemed to be nothing but inert mineral yet was very potent in infecting tobacco. It was incredible to biologists that any purely mineral solid, chemically cooked and rigorously reduced for more than two years until obviously "dead," could still carry and spread a disease, but the dry crystals turned out to be about 95 percent protein and 5 percent nucleic acid and perfectly capable, in the presence of tobacco leaf cells, of reproducing themselves scores of times in an hour.
Before we get ahead of our story, however, I must point out that the resolution of this major mystery in what seemed to be the ultimate microbe will have to await Chapter 6.
CELLS
Here is where we need to take a look at what is coming to be recognized as the basic unit of life, the cell. Cells have not been easy to investigate, being generally invisible and therefore quite unsuspected by man until A.D. 1665 when Robert Hooke happened to notice their compartmented structure while examining pieces of cork under his low-powered pre-Leeuwenhoek "microscope." The segments presumably reminded him so much of monks' cells in a monastery that he naturally named them cells also. But although he drew detailed pictures of them, he did not realize they were present in all plants and animals. In fact it was not until 1839 that the botanist Matthias Jakob Schleiden and the zoologist Theodor Schwann propounded the startling theory that the cell is the "vessel of living matter," a new idea for which Rudolf Virchow was to win wide acceptance in 1859 by demonstrating that all cells, in both vegetables and animals, originate from the divisions of earlier cells. In other words, the cell at last was revealed as the natural unit of life, not only capable of independence as a complete one-celled animal like an ameba or a paramecium, but surprisingly independent even when part of a large multicelled organism, feeding, excreting, reproducing and in many cases moving about and making responsive decisions. In a nourishing liquid (known as a "tissue culture") almost any body cell can now be kept alive outside the body, like the free creature many of its ancestors must have been millions of years ago, and this discovery in the early 1930s convinced biolog
ists that cells must be much more than the simple blobs of jelly they appeared.
If you have never seen a body cell floating by itself in a tissue culture, I might say that at first the ovoid speck usually seems inert and helpless, drifting idly off after separation from that greater organism, its multiceiled body society. But as soon as the lonely cell touches a solid object it responds. Perceptibly it bulges toward it. Then a protoplasmic finger forms on the cell, pointing and reaching out in the direction it wants to go. If the solid object is the inside surface of a test tube, the fingertip usually flattens against it, gluing itself to the glass. Then the finger contracts, pulling the rest of the cell toward that glued spot. The cell then normally takes a second step as another finger reaches forward, and thus it creeps with apparent purpose on its way.
Startled to find such unexpected deliberation in human flesh, biologists have been pursuing the cell with more and more powerful microscopes ever since, eagerly exploring its mysterious spots and shadows to learn how this curious unit organism functions. In the 1940s they discovered a faint but persistent stringiness in the protoplasm near the nucleus that eventually proved to be a complicated and beautiful network of tubes and necklaces, through which the teeming cell populace of porters and messengers could be detected flowing like Street traffic in all directions, delivering supplies and orders to every part of the cell and of course to a great extent beyond it among adjoining cells and the outside world. The beads on the necklaces (some of them loose beads) in turn were found to be individual chemical generators, soon named mitochondria, which are endlessly turning out the dynamic fuel adenosine triphosphate, now commonly abbreviated ATP, a very ancient kind of bio-explosive that powers all of life's material activity from growth to muscle contraction and is, as you may remember, a vital step in the chemistry of photosynthesis.
Between and all around the tubes, necklaces and other special parts is the real interior space of the cell, a sort of storage place that serves also as a lobby and reading room, where fat vacuoles loll about full of water, oil or gruel and curious enzymes are stacked like books and periodicals on library shelves. The most useful "volumes" are continually being passed and circulated about the cell corridors while an important percentage are confidently dispatched abroad like overseas mail in the form of explicit messages, in effect written, coded and posted by one cell to a fellow cell it has never seen but somehow manages to correspond with, even while they are worlds apart.
The key to this enzyme library is located, as long suspected, in the cell's nucleus in the form of a master code, a code literally made of genes and guarded like a state secret. The nucleus that encloses it turns out to be a sort of cell manager's office built like a vault, out of which painstakingly accurate copies of the cell's construction plans are rolling off the duplicating machines at speed for immediate distribution to ensure that every part of the cell knows what is expected of it and that not only all parts of the cell but all cells of a whole multicelled organism conform to the same standard. The very difficult job of cracking the cell's genetic code was only undertaken in the 1950s after scientists practically blasted their way into its nucleus and extracted the key substance of deoxyribonucleic acid which, by popular demand, was quickly abbreviated to DNA. The heart of the nucleus of every cell, they found, is essentially a tapelike coil of DNA that carries the code of life in it as surely as a magnetic tape carries a speech or a tune. DNA however is not only more indelible than magnetic tape but there is something unquestionably mystic about it. In fact, while ruling the cell by regulating its chemicals and dispatching its enzymes, DNA subtly conceals the ultimate origin of its power. In a way DNA acts as the cell's god, a designation appropriately spelled out in the Latin word deo, which forms the first three letters of deoxyribonucleic acid. And, godlike, it broadcasts its omnific decrees at electronic speed through a technique so intricate and awesome we must defer looking deeply into it until Chapter 6.
I can say here, however, that DNA's decrees are translated into action with an elegance and perfection evolved over billions of years, a micro-majesty perhaps best exemplified by the cell's oft-repeated but deliberate division into two daughter cells. This kind of dividing is called mitosis and is a normal act of growth that is happening in millions of places in your body at every moment. If you've ever wondered why big animals, say whales, don't multiply this way, splitting down the middle to produce two new half-sized whales, thereby circumventing the problems of babyhood, it's because the whales would have to be genetically the same. They would inevitably be identical twins and identical not only with each other but also with their parent. Which would be disastrous from the standpoint of evolution because evolution needs continuous variation in order to be flexible enough to adapt to changing conditions.
Mitosis, on the other hand, is just right for cells. Being in the microcosm and therefore very numerous, cells don't need to be flexible individually but only in statistical masses. Besides, the heirlooms of cells, unlike macrocosmic davenports and teapots that would be damaged by being cut in two, can safely be split into identical halves right down to the chromosome and gene levels. And that actually is how their bequests are bequeathed. It is an orderly, even stately, performance taking about an hour in each case, displaying a discipline, beauty and wisdom hard to imagine as springing solely from that microscopic cell. First there comes a sort of secret decision that whispers forth a quiet mobilization order that rapidly grips the whole cell in a state of pseudo crystallization. This begins just outside the nucleus at a spot called the centriole, from which tiny lines are seen to shoot out like frost feathers across a windowpane, lines (probably representing microscopic fibers) that in a few minutes have organized the whole cell into two halves around two poles that appear as mirror images of each other. This polarity of course includes the nucleus, which, following the rest of the cell, progressively straightens and regiments its coils of DNA into duplicate forms, each paired member attached to an opposite centriole by threads that converge on it as if wound on spindles in a textile mill. When the whole cell is thus completely regimented into the mirrored double-crystal form, an equator of cleavage appears halfway between the poles, a bulbous waistline that begins to pinch inward as the upper and lower hemispheres pull apart, eventually thinning to a tight waspish shape before they finally separate into two new round cells (illustrated on page 164).
You might think these twin baby cells would rest for a day or two after their birth, but no, their nature is to move and, as long as they are free, they keep moving at an average speed about equal to the hour hand of a small watch. Furthermore each one is under some mysterious compulsion to make a crucial decision within its first two or three hours: it must either begin to specialize, after which it may never divide again, or start to divide and subdivide further, in which case each time it cleaves into children it will also "conceive" grandchildren in the children's centrioles. By such rules do cells in general - vegetable as well as animal ones and including the 50 trillion cells in your body - live and renew themselves, diversifying the while into flesh, leaf, bone, wood, blood, muscle, nerves, skin, bark, hair, seed, eyes and all the other substances needed. And despite, or because of, their restless activity, each one somehow always seems to be in an appropriate place at every moment of its life, a life whose duration depends largely on the role it has chosen to play, the role in turn normally conforming to whatever specialized cells it has been associated with. Thus unspecialized vertebrate cell tissue, if exposed to a piece of spinal cord, will nearly always start producing cartilage tissue, a first step toward becoming a spine. Yet the same unspecialized tissue, embedded instead in muscle, will in more than 99 cases out of 100 rapidly specialize into muscle cells.
As to what actually makes a cell begin to specialize, very little is known, but biologists have noticed that body cells on the loose commonly sprout sensitive whiskers they call microspikes or pili, which whisk about and feel what is near them and, if it is congenial, penetrate and cling to i
t. Presumably it is these tentacles (more than any other factor) that enable cells to spot and scrape acquaintance with their neighbors, whereupon, assuming the neighbors "taste" good, they flock together with them into the dense masses familiar to us as flesh and bone, at the same time exchanging genetic material and perhaps exuding short-range chemical bonds for greater cohesion, like a kind of living mortar.
There is no reason to suppose the individual cell has any real choice as to whether it will specialize and settle down as part of a gut or a leg or an eye in this social development, which may resemble a well-rehearsed army mobilization, but, as I said, it obviously makes a lot of difference in the expectable life spans of its descendants. For an epithelial cell in the gut lining lives only a day or two before it dies and is sloughed off, but white blood cells can last two weeks and red ones four months. Nerve cells, however, which cannot normally be replaced at all, may survive more than a hundred years - a decidedly opportune span in the case of centenarians, who depend, like the rest of us, on irreplaceable nerves.