by Isaac Asimov
MAGNIFYING DEVICES
Had anyone suspected such a thing, people might have come much sooner to the deliberate use of magnifying devices. Even the Greeks and Romans knew that glass objects of certain shapes would focus sunlight on a point and would magnify objects seen through the glass. A hollow glass sphere filled with water would do so, for instance. Ptolemy discussed the optics of burning glasses; and Arabic writers such as Alhazen, about 1000 A.D., extended his observations.
It was Robert Grosseteste—English bishop, philosopher, and keen amateur scientist—who, early in the thirteenth century, first suggested a use for this. He pointed out that lenses (so named because they were shaped like lentils) might be useful in magnifying objects too small to be seen conveniently. His pupil Roger Bacon acted on this suggestion and devised spectacles to improve poor vision.
At first only convex lenses, to correct farsightedness, were made. Concave lenses, to correct nearsightedness, were not developed until about 1400. The invention of printing brought more and more demand for spectacles; and by the sixteenth century spectacle making was a skilled profession. It became a particular specialty in the Netherlands.
(Bifocals, serving for both far and near vision, were invented by Benjamin Franklin in 1760. In 1827, the British astronomer George Biddell Airy designed the first lenses to correct astigmatism, from which he suffered himself. And in 1887, a German physician, Adolf Eugen Fick, introduced the idea of contact lenses, which may some day make ordinary spectacles more or less obsolete.)
Let us get back to the Dutch spectaclemakers. In 1608, so the story goes, an apprentice to a spectaclemaker named Hans Lippershey, amused himself during an idle hour by looking at objects through two lenses held one behind the other. The apprentice was amazed to find that, when he held them a certain distance apart, far-off objects appeared close at hand. The apprentice promptly told his master about it, and Lippershey proceeded to build the first telescope, placing the two lenses in a tube to hold them at the proper spacing. Prince Maurice of Nassau, commander of the Dutch forces in rebellion against Spain, saw the military value of the instrument and endeavored to keep it secret.
He reckoned without Galileo, however. Hearing rumors of the invention of a far-seeing glass, and knowing no more than that it was made with lenses, Galileo soon discovered the principle and built his own telescope; his was completed within six months after Lippershey’s.
By rearranging the lenses of his telescope, Galileo found that he could magnify close objects, so that it was in effect a microscope. Over the next decades, several scientists built microscopes. An Italian naturalist named Francesco Stelluti studied insect anatomy with one; Malpighi discovered the capillaries; and Hooke discovered the cells in cork.
But the importance of the microscope was not really appreciated until Anton van Leeuwenhoek, a merchant in the city of Delft, took it up. Some of van Leeuwenhoek’s lenses could enlarge up to 200 times.
Van Leeuwenhoek looked at all sorts of objects quite indiscriminately, describing what he saw in lengthy detail in letters to the Royal Society in London. It was rather a triumph for the democracy of science that the tradesman was elected a fellow of the gentlemanly Royal Society. Before he died, the Queen of England and Peter the Great, czar of all the Russias, visited the humble microscope maker of Delft.
Through his lenses van Leeuwenhoek discovered sperm cells and actually saw blood moving through capillaries in the tail of a tadpole. More important, he was the first to see living creatures too small to be seen by the unaided eye. He discovered these animalcules in stagnant water in 1675. He also resolved the tiny cells of yeast and, at the limit of his lenses’ magnifying power, finally, in 1676, came upon germs, which today we know as bacteria.
Microscopes improved only slowly, and it took a century and a half before objects the size of germs could be studied with ease. For instance, it was not until 1830 that the English optician Joseph Jackson Lister devised an achromatic microscope, which eliminated the rings of color that limited the sharpness of the image. Lister found that red-blood corpuscles (first detected as featureless blobs by the Dutch physician Jan Swammerdam in 1658) were biconcave disks-like tiny doughnuts with dents instead of a hole. The achromatic microscope was a great advance; and in 1878, the German physicist Ernst Abbé began a series of improvements that resulted in what might be called the modern optical microscope.
NAMING THE BACTERIA
The members of the new world of microscopic life gradually received names. Van Leeuwenhoek’s animalcules actually were animals, feeding on small particles and moving about by means of small whips (flagellae) or hairlike cilia or advancing streams of protoplasm (pseudopods). These animals were given the name protozoa (Greek for “first animals”), and the German zoologist Karl Theodor Ernst Siebold identified them as single-celled creatures.
Germs were something else-much smaller than protozoa and much simpler.
Although some germs could move about, most lay quiescent and merely grew and multiplied. Except for their lack of chlorophyll, they showed none of the properties associated with animals. For that reason, they were usually classified among the fungi—plants that lack chlorophyll and live on organic matter. Nowadays most biologists tend to consider germs as neither plant nor animal but as a class by themselves. Germ is a misleading name for them. The same term may apply to the living part of a seed (as in “wheat germ”), or to sex cells (“germ cells”), or to embryonic organs (“germ layers”), or, in fact, to any small object possessing the potentiality of life.
The Danish microscopist Otto Frederik Muller managed to see the little creatures well enough in 1773 to distinguish two types: bacilli (from a Latin word meaning “little rods”) and spirilla (for their spiral shape). With the advent of achromatic microscopes, the Austrian surgeon Theodor Billroth saw still smaller varieties to which he applied the term coccus (from the Greek word for “berry”). It was the German botanist Ferdinand Julius Cohn who finally coined the name bacterium (also from a Latin word meaning “little rod”). (See figure 14.1.)
Figure 14.1. Types of bacteria: cocci (A), bacilli (B), and spirilla (C). Each type has a number of varieties.
Pasteur popularized the general term microbe (“small life”) for all forms of microscopic life—plant, animal, and bacterial. But this word was soon adopted for the bacteria, just then coming into notoriety. Today the general term for microscopic forms of life is microorganism.
The larger microorganisms are eukaryotes, as are the cells of multicellular animals and plants (including our own). The protozoa have nuclei and mitochondria, together with other organelles. Indeed, many of the protozoan cells are larger and more complex than the cells of our own body, for instance, since the protozoan cell must perform all the functions inseparable from life, whereas the cells of multicellular organisms may specialize and depend on other cells to perform functions and supply products they themselves cannot.
One-celled plant cells, called algae are, again, as complex as the cells of multicellular plants or more so. The algae contain nuclei, chloroplasts, and so on.
Bacteria, however, are prokaryotes and do not contain a nucleus or other organelles. The genetic material, ordinarily confined within the nucleus in eukaryotes, is spread throughout the bacterial cell. Bacteria are also unique in possessing a cell wall made up chiefly of a polysaccharide and protein in combination. Bacteria, which range from 1 to 10 micrometers in diameter (averaging, in other words, about 1/10,000th of an inch in diameter), are much smaller than eukaryotic cells in general.
Another large group of prokaryotes are the blue-green algae, which differ from bacteria chiefly in possessing chlorophyll and being able to carry through photosynthesis. Sometimes these are simply called blue-greens, leaving the term algae for eukaryotic one-celled plants.
One must not be overwhelmed by the apparent simplicity of bacteria. Although they do not have nuclei and do not seem to transfer chromosomes in the fashion of sexual reproduction, they nevertheless do ind
ulge in a kind of primitive sex. In 1946, Edward Tatum and his student Joshua Lederberg began a series of observations that showed that bacteria do, on occasion, transfer sections of nucleic acid from one individual to another. Lederberg called the process conjugation, and he and Tatum shared in the 1958 Nobel Prize for physiology and medicine as a result.
In the study of conjugation, it appeared that the portions of the nucleic acid that underwent transfer were molecules that formed rings rather than straight lines. In 1952, Lederberg named these nucleic acid rings plasmids. The plasmids are the nearest thing to organelles that bacteria have. They possess genes, control the formation of certain enzymes, and can transfer properties from cell to cell.
THE GERM THEORY OF DISEASE
It was Pasteur who first definitely connected microorganisms with disease, thus founding the modern science of bacteriology or, to use a more general term, microbiology. This came about through Pasteur’s concern with something that seemed an industrial problem rather than a medical one. In the 1860s, the French silk industry was being ruined by a disease of the silkworms. Pasteur, having already rescued France’s wine makers, was put to work on this problem, too. Again making inspired use of the microscope, as he had in studying asymmetric crystals and varieties of yeast cells, Pasteur found microorganisms infecting the sick silkworms and the mulberry leaves on which they fed. He recommended that all infected worms and leaves be destroyed and a fresh start be made with the uninfected worms and leaves that remained. This drastic step was taken, and it worked.
Pasteur did more with these researches than merely to revive the silk industry. He generalized his conclusions and enunciated the germ theory of disease—without question the greatest single medical discovery ever made (and it was made not by a physician but by a chemist, as chemists such as myself delight in pointing out).
Before Pasteur, doctors had been able to do little more for their patients than recommend rest, good food, fresh air, and clean surroundings and, occasionally, handle a few types of emergency. This much had been advocated by the Greek physician Hippocrates of Cos (the “father of medicine”) as long ago as 400 B.C. It was Hippocrates who introduced the rational view of medicine, turning away from the arrows of Apollo and demonic possession to proclaim that even epilepsy, called the “sacred disease,” was not the result of being affected by some god’s influence, but was a mere physical disorder to be treated as such. The lesson was never entirely forgotten by later generations.
However, medicine progressed surprisingly little in the next two millennia. Doctors could lance boils, set broken bones, and prescribe a few specific remedies that were simply products of folk wisdom: such drugs as quinine from the bark of the cinchona tree (originally chewed by the Peruvian Indians to cure themselves of malaria), and digitalis from the foxglove plant (an old herbwomen’s remedy to stimulate the heart). Aside from these few treatments (and the smallpox vaccine, which I shall discuss later), many of the medicines and treatments dispensed by physicians after Hippocrates tended to heighten the death rate rather than lower it.
One of the interesting advances made in the first two and a half centuries of the Age of Science was the invention, in 1819, of the stethoscope by the French physician, René Théophile Hyacinthe Laennec. In its original form, it was little more than a wooden tube designed to help the doctor hear and interpret the sounds of the beating heart. Improvements since then have made it as characteristic and inevitable an accompaniment of the physician as the pocket computer is of an engineer.
It is not surprising, then, that up to the nineteenth century, even the most civilized countries were periodically swept by plagues, some of which had a profound effect on history. The plague in Athens that killed Pericles, at the time of the Peloponnesian War, was the first step in the ultimate ruin of Greece. Rome’s downfall probably began with the plagues that fell upon the empire during the reign of Marcus Aurelius. The Black Death of the fourteenth century is estimated to have killed off a fourth of the population of Europe; this plague and gunpowder combined to destroy the social structure of the Middle Ages.
To be sure, plagues did not end when Pasteur discovered that infectious diseases are caused and spread by microorganisms. In India, cholera has long been endemic, and other underdeveloped countries suffer severely from epidemics. Disease has remained a major hazard of wartime. Virulent new organisms arise from time to time and sweep over the world; indeed, the influenza pandemic of 1918 killed an estimated 15 million people, a larger number of people than died in any other plague in human history, and nearly twice as many as were killed in the then just-completed world war.
Nevertheless, Pasteur’s discovery was a great turning point. The death rate in Europe and the United States began to fall markedly, and life expectancy steadily rose. Thanks to the scientific study of disease and its treatment, which began with Pasteur, men and women in the more advanced regions of the world can now expect to live an average of over seventy years; whereas before Pasteur, the average was only forty years under the most favorable conditions and perhaps only twenty-five years under unfavorable conditions. Since the Second World War, life expectancy has been zooming upward even in the less advanced regions of the world.
IDENTIFYING BACTERIA
Even before Pasteur advanced the germ theory in 1865, a Viennese physician named Ignaz Philipp Semmelweiss had made the first effective attack on bacteria, without, of course, knowing what he was fighting. He was working in the maternity ward of one of Vienna’s hospitals, where 12 percent or more of the new mothers died of something called puerperal fever (in plain English, “childbed fever”). Semmelweiss noted uneasily that women who bore their babies at home, with only the services of ignorant midwives, practically never got puerperal fever. His suspicions were further aroused by the death of a doctor in the hospital with symptoms that strongly resembled those of puerperal fever, after the doctor had cut himself while dissecting a cadaver. Were the doctors and students who came in from the dissection wards somehow transmitting this disease to the women whose delivery they attended? Semmelweiss insisted that the doctors wash their hands in a solution of chlorinated lime. Within a year, the death rate in the maternity wards fell from 12 percent to 1.5 percent.
But the veteran doctors were livid. Resentful of the implication that they had been murderers, and humiliated by all the hand washing, they drove Semmelweiss out of the hospital. (They were helped by the fact that he was a Hungarian, and Hungary was in revolt against its Austrian rulers.) Semmelweiss went to Budapest, where he reduced the maternal death rate; while in Vienna, the hospitals reverted to death traps for another decade or so. But Semmelweiss himself died of puerperal fever from an accidental infection (at the age of forty-seven) in 1865—just too soon to see the scientific vindication of his suspicions about the transmission of disease. That was the year when Pasteur discovered microorganisms in the diseased silkworms, and when an English surgeon named Joseph Lister (the son of the inventor of the achromatic microscope) independently introduced the chemical attack upon germs.
Lister resorted to the drastic substance phenol (carbolic acid). He used it first in dressings for a patient with a compound fracture. Up to that time, any serious wound almost invariably led to infection. Of course, Lister’s phenol killed the tissues around the wound, but it did kill the bacteria. The patient made a remarkably untroubled recovery.
Lister followed up this success with the practice of spraying the operating room with phenol. It must have been hard on people who had to breathe it, but it began to save lives. As in Semmelweiss’s case, there was opposition, but Pasteur’s experiments had created a rationale for antisepsis, and Lister easily won the day.
Pasteur himself had somewhat harder going in France (unlike Lister, he lacked the union label of the M.D.), but he prevailed on surgeons to boil their instruments and steam their bandages. Sterilization with steam à la Pasteur replaced Lister’s unpleasant phenol spray. Milder antiseptics, which could kill bacteria without unduly damag
ing tissue, were sought and found. The French physician Casimir Joseph Davaine reported on the antiseptic properties of iodine in 1873, and tincture of iodine (that is, iodine dissolved in a mixture of alcohol and water) came into common use in the home. It and similar products are automatically applied to every scratch. The number of infections prevented in this way is undoubtedly enormous.
In fact, the search for protection against infection leaned more and more in the direction of preventing germ entry (asepsis) rather than of destroying germs after they had gained a foothold, as was implied in antisepsis. In 1890, the American surgeon William Stewart Halstead introduced the practice of using sterilized rubber gloves during operations; by 1900, the British physician William Hunter had added the gauze mask to protect the patient against the germs in the physician’s breath.
Meanwhile the German physician Robert Koch had begun to identify the specific bacteria responsible for various diseases, by introducing a vital improvement in the nature of culture media—that is, the food supply in which bacteria are grown. Where Pasteur used liquid media, Koch introduced solid media. He planted isolated samples on gelatin (for which agar, a gelatinlike substance obtained from seaweed, was substituted later). If a single bacterium is deposited (with a fine needle) in a spot on this medium, a pure colony will grow around the spot, because on the solid surface of the agar the bacteria lacks the ability to move or drift away from the original parent, as they would do in a liquid. An assistant of Koch, Julius Richard Petri, introduced the use of shallow glass dishes with covers, to protect the cultures from contamination by bacterial spores floating in air; such Petri dishes have been used for the purpose ever since.
