From the archives: The germ theory of disease breaks through

Imperfect but important, the seminal lecture on the origins of disease appeared in the 1883 issue of Popular Science Monthly.
An excerpt from the famous germ theory of disease lecture
"The germ theory of disease" by H. Gradle, M.D, September 1883 Popular Science

To mark our 150th year, we’re revisiting the Popular Science stories (both hits and misses) that helped define scientific progress, understanding, and innovation—with an added hint of modern context. Explore the entire From the Archives series and check out all our anniversary coverage here.

Germs first came into focus, literally, under the microscope of Robert Koch, a doctor practicing in East Prussia in the 19th century. Until then, as Popular Science reported in September 1883, getting sick was attributed to everything from evil spirits to “impurities of the blood.” Koch first eyed Bacillus anthracis, or anthrax, in animal tissue in 1877, from which he linked microbes with disease. But it was his isolation of Mycobacterium tuberculosis in 1881—then known as consumption—that set off an avalanche of germ discovery. 

In the 1880s alone, Koch and others cataloged a slew of plagues: cholera (1883), salmonella (1884), diphtheria (1884), pneumonia (1886), meningitis (1887), and tetanus (1889). By 1881, Louis Pasteur, a French chemist, had already developed the world’s first vaccine, used on sheep to prevent anthrax.

Henry Gradle, a Chicago physician and the author of Popular Science’s 1883 “The Germ-Theory of Disease” (originally delivered as a lecture to the Chicago Philosophical Society in November, 1882) had been a pupil under Koch and brought word of the German and French discoveries to the US and UK. Gradle writes with great flourish, not holding back his disdain for those who disagreed with the new germ theory, likening them to “savages” of human antiquity who saw only “evil spirits in disease”—as vulgar as such phrases are in a modern context. 

Although now considered a watershed moment for medicine, at the time, germ theory had gaping holes, including an understanding of the immune system’s role in disease. Antoine Béchamp, a chemist and Pasteur’s bitter rival, argued that it was not germs but the state of the host (the patient) that caused illness otherwise, he noted, everyone would be sick all the time. Béchamp had his followers who stood fast against the germ theory. 

As Thomas Kuhn, a noted scientific philosopher, proposed in his 1962 essay, The Structure of Scientific Revolutions, paradigm shifts like germ theory were “revolutions,” because they shook both science and society.

“The germ theory of disease” (H. Gradle, M.D, September 1883)

Scourages of the human race and diseases are attributed by savages to the influence of evil spirits. Extremes often meet. What human intelligence suspected in its first dawn bas been verified by human intelligence in its highest development. Again, we have come to the belief of evil spirits in disease, but these destroyers have now assumed a tangible shape. Instead of the mere passive, unwitting efforts with which we have hitherto resisted them, we now begin to fight them in their own domain with all the resources of our intellect. For they are no longer invisible creatures of our own imagination, but with that omnipotent instrument, the microscope, we can see and identify them as living beings, of dimensions on the present verge of visibility. The study of these minute foes constitutes the germ theory. 

This germ theory of disease is rising to such importance in medical discussions that it cannot be ignored by that part of the laity who aspire to a fair general information. For it has substituted a tangible reality for idle speculation and superstition so current formerly in the branch of medical science treating the causes of disease. Formerly—that is, within a period scarcely over now—the first cause invoked to explain the origin of many diseases was the vague and much-abused bugbear “cold.” When that failed, obscure chemical changes, of which no one knew anything definitely, or “impurities of the blood,” a term of similar accuracy and convenience, were accused, while with regard to contagious diseases medical ignorance concealed itself by the invocation of a “genus epidemicus.” The germ theory, as far as it is applicable, does away with all these obscurities. It points out the way to investigate the causes of disease with the same spirit of inquiry with which we investigate all other occurrences in nature.  In the light of the germ theory, disease is a struggle for existence between the parts of the organism and some parasite invading it. From this point of view, diseases become a part of the Darwinian program of nature.

The animal body may be compared to a vast colony, consisting as it docs of a mass of cells the ultimate elements of life. Each tissue, be it bone, muscle, liver, or brain, is made up of cells of its own kind, peculiar to and characteristic of the tissue. Each cell represents an element living by itself, but capable of continuing its life only by the aid it gets from other cells. By means of the blood vessels and the nervous system, the different cells of the body are put into a state of mutual connection and dependence. The animal system resembles in this way a republic, in which each citizen depends upon others for protection, subsistence, and the supply of the requisites of daily life. Accustomed as each citizen is to this mutual interdependence, he could not exist without it. Each citizen of this animal colony, each cell, can thrive only as long as the conditions persist to which it is adapted. These conditions comprise the proper supply of food and oxygen, the necessary removal of the waste products formed by the chemical activity of all parts of the body, the protection against external mechanical forces and temperature, as well as a number of minor details. Any interference with these conditions of life impairs the normal activity of the entire body, or, as the case may be, of the individual cells concerned. But the animal system possesses the means of resisting damaging influences. Death or inactivity of one or a few citizens does not disable the state. The body is not such a rigid piece of mechanism that the breakage of one wheel can arrest the action of the whole. Within certain limits, any damage done to individual groups of cells can be repaired by the compensating powers of the organism. It is only when this compensating faculty fails, when the body can not successfully resist an unfavorable influence, that a disturbance arises which we call disease. This definition enables us to understand how external violence, improper or insufficient food, poisons, and other unaccustomed influences, can produce disease. But modern research has rendered it likely that the diseases due to such causes are not so numerous as the affections produced by invasion of the body by parasites.

Of these a few are known to be animals―for instance, the trichina, and some worms found in the blood in certain rare diseases. But the bulk of the hosts we have to contend with is of vegetable nature, and belongs to the lowest order of fungi-commonly termed bacteria.

Special names have been given to the different subdivisions of this class of microscopic beings―the rod-shaped bacteria being termed bacilli; the granular specimens, micrococci; while the rarer forms, of the shape of a screw, arc known as spirilla.

Bacteria surround us from all quarters. The surface of the earth teems with them. No terrestrial waters are free from them. They form a part of the atmospheric dust, and are deposited upon all objects exposed to the air. It is difficult to demonstrate this truth directly with the microscope, for in the dry state bacteria are not readily recognized, especially when few in number. But we can easily detect their presence by their power of multiplication. We need but provide a suitable soil. An infusion of almost any animal or vegetable substance will suffice―meat broth, for instance―though not all bacteria will grow in the same soil. Such a fluid when freshly prepared and filtered, is clear as crystal, and remains so if well boiled and kept in a closed vessel, for boiling destroys any germs that may be present, while the access of others is prevented by closure of the flask. But as soon as we sow in this fluid a single bacterium, it multiplies to such an extent that within a clay the fluid is turbid from the presence of myriads of microscopic forms. For this purpose we can throw in any terrestrial object which has not been heated previously, or we can expose the fluid to the dust of the air. Air which has lost its dust by subsidence or filtration through cotton has not the power of starting bacterial life in a soil devoid of germs. Of course, the most certain way of filling our flask with bacteria is to introduce into it a drop from another fluid previously teeming with them.

In a suitable soil each bacterium grows and then divides into two young bacteria, it may be within less than an hour, which progeny continue the work of their ancestor. At this rate a single germ, if not stinted for food, can produce over fifteen million of its kind within twenty-four hours! More astounding even seems the calculation that one microscopic being, some forty billion of which can not weigh over one grain, might grow to the terrific mass of eight hundred tons within three days, were there but room and food for this growth!

During their growth the bacteria live upon the fluid, as all other plants do upon their soil. Characteristic, however, of bacteria-growth is the decomposition of any complex organic substances in the fluid to an extent entirely disproportionate to the weight of the bacteria themselves. This destructive action occurs wherever bacteria exist, be it in the experimental fluid, or in the solid animal or vegetable refuse where they are ordinarily found. It constitutes, in fact, rotting or putrefaction. The processes of decomposition of organic substances coming under the head of putrefaction are entirely the effect of bacterial life. Any influence, like heat, which kills the bacteria, arrests the putrefaction, and the latter does not set in again until other living bacteria gain access to the substance in question. Without bacteria, no putrefaction can occur, though bacteria can exist without putrefaction, in case there is no substance on hand which they can decompose.

No error has retarded more the progress of the germ theory than the false belief that the bacteria of putrefaction are identical with the germs of disease. The most contradictory results were obtained in experiments made to demonstrate on animals either the poisonous nature, or, on the other hand, the harmlessness, of the fungi commonly found in rotting refuse. But real contradictions do not exist in science; they are only apparent, because the results in any opposite eases were not obtained under identical conditions. The explanation of the variable effects of common putrefaction―germs upon animals is self-evident as soon as we admit that each parasitic disease is due to a separate species of bacteria, characteristic of the disease, producing only this form and no other affection; while, on the other band, the same disease can not be caused by any other but its special parasite. It can be affirmed, on the basis of decisive experiments, that the bacteria characteristic of various diseases float in the air, in many localities at least. Hence rotting material, teeming with bacterial life, may or may not contain disease-producing germs, according to whether the latter have settled upon it by accident or not.  Even if these disease-­producing species were as numerous in the dust as the common bacteria of putrefaction, which we do not know, they would be at a disadvantage, as far as their increase is concerned. For experience has shown that the germs of most diseases require a special soil for their growth, and can not live, like the agents of putrefaction, upon any organic refuse. In some cases, indeed, these microscopic parasites are so fastidious in their demands that they can not grow at all outside of the animal body which they are adapted to invade. Renee, if a decomposing fluid does contain them, they form at least a minority of the inhabitants, being crowded out by the more energetically growing forms. In the microscopic world there occurs as bitter a struggle for existence as is ever witnessed between the most highly organized beings. The species best adapted to the soil crowds out all its competitors.

Though the putrefaction bacteria, or, as Dumas calls them, the agents of corruption, are not identical with disease-producing germs, they are yet not harmless by themselves. Putrid fluids cause grave sickness when introduced into the blood of animals in any quantity. But this is not a bacterial disease proper; it is an instance of poisoning by certain substances produced by the life-agency of the bacteria while decomposing their soil. The latter themselves do not increase in the blood of the animal; they are killed in their struggle with the living animal cells. The putrefaction-bacteria need not be further present in the putrid solution to produce the poisonous effect on animals. They may be killed by boiling, if only the poisonous substances there formed remain.

In order to prove the bacterial origin of a disease two requirements are necessary: First, we must detect the characteristic bacteria in every case of that disease; secondly, we must reproduce a disease in other individuals by means of the isolated bacteria of that disease. Both these demonstrations may be very difficult. Some species of bacteria are so small and so transparent that they can not be easily, if at all, seen in the midst of animal tissues. This difficulty may be lessened by the use of staining agents, which color the bacteria differently from the animal cells. But it often requires long and tedious trials to find the right dye. The obstacles in the way of the second part of the proposition mentioned are no less appalling. Having found a suspected parasite in the blood or flesh of a patient, we can not accuse the parasite with certainty of being the cause of the disease, unless we can separate it entirely from the fluids and cells of the diseased body without depriving it of its virulence. In some cases it is not easy, if possible, to cultivate the parasite outside of the body; in other instances it can be readily accomplished. Of course, all such attempts require scrupulous care to prevent contamination from other germs that might accidentally be introduced into the same soil. If we can now reproduce the original disease in other animals by infection with these isolated bacteria, the chain of evidence is complete beyond cavil and doubt. But this last step may not be the least difficult, as many diseases of mankind can not be transferred to animals, or only to some few species.

If we apply these rigid requirements, there are not many diseases of man whose bacterial origin is beyond doubt. As the most unequivocal instance, we can mention splenic fever, or anthrax, a disease of domestic animals, which sometimes attacks man, and is then known as malignant pustule. The existence of a parasite in this affection in the form of minute rods and its power of reproducing the disease are among the best-established facts in medicine. It is also known that these rods form seeds, or spores, as they are termed, in their interior, after the death of the patient, which germinate again in proper soil. These spores are the most durable and resisting objects known in animated nature. If kept in the state of spores they possess an absolute immortality; no temperature short of prolonged boiling can destroy them, while they can resist the action of most poisons, even corrosive acids, to a scarcely credible extent.

Another disease, of vastly greater importance to man, has lately been added to the list of scourges of unquestionable bacterial origin. I refer to tuberculosis, or consumption. It is true, this claim is based upon the work of but one investigator―Robert Koch. But whoever reads his original description must admit that no dart of criticism can assail his impenetrable position. Here also a rod-shaped bacillus, extremely minute and delicate, has been found the inevitable companion of the disease. With marvelous patience Koch has succeeded in getting the parasite to grow in pure blood, and freeing it from all associated matter.  It must have been a rare emotion that filled the soul of that indefatigable man, when he beheld for the first time, in its isolated state, the fell destroyer of over one eighth of all mankind! None of the animals experimented upon could withstand the concentrated virulence of the isolated parasite. This bacillus likewise produces spores of a persistent nature, which every consumptive patient spits broadcast into the world.

Relapsing fever is another disease of definitely proved origin. If we mention, furthermore, abscesses, the dependence of which on bacteria has lately been established, we have about exhausted the list of human afflictions about the cause of which there is no longer any doubt. Some diseases peculiar to lower animals belong also to this category. The classical researches of Pasteur have assigned the silkworm disease and chicken cholera to the same rank. Several forms of septicemia and pyemia have also been studied satisfactorily in animals. Indeed, the analogy between these and the kindred forms of blood-poisoning in man is so close that there can be no reasonable doubt as to the similarity of cause. This assumption, next door to certainty, applies equally to the fevers of childbirth. The experimental demonstration of the parasitic nature of leprosy, erysipelas, and diphtheria is not yet complete, though nearly so. Malarial fever also is claimed to belong to the category of known bacterial diseases, but the proofs do not seem as irreproachable to others as they do to their authors.

The entire class of contagious diseases of man can be suspected on just grounds of being of bacterial origin. All analogies, and not a few separate observations, are in favor of this view, while against it no valid argument can be adduced; but it must be admitted that the absolute proof is as yet wanting. Many diseases also, not known to be contagious, like pneumonia, rheumatism, and Bright’s disease, have been found associated with parasites, the role of which is yet uncertain. It is not sophistry to look forward to an application of the germ theory to all such diseases, if only for the reason that we know absolutely no other assignable cause, while the changes found in them resemble those known to be due to parasites. In the expectation of all who are not blinded by prejudice, the field is a vast one, which the germ theory is to cover some day, though progress can only continue if we accept nothing as proved until it is proved.

There can be little doubt that in many, perhaps in most instances, the disease-producing germs enter the body with the air we breathe. At any rate, the organism presents no other gate so accessible to germs as the lungs. Moreover, it has been shown that an air artificially impregnated with living germs can infect animals through the lungs. How far drinking water can be accused of causing sickness as the vehicle of parasites can not be stated with certainty. There is, as yet, very little evidence to the point, and what there is is ambiguous. Thus, exposed from all quarters to the attacks of these merciless invaders, it seems almost strange that we can resist their attacks to the extent that we do. In fact, one of the arguments used against the germ theory―a weak one, it is true―is, that, while it explains why some fall victims to the germs, it does not explain why all others do not share their fate. If all of us are threatened alike by the invisible enemies in the air we breathe, how is it that so many escape? If we expose a hundred flasks of meat-broth to the same atmosphere, they will all become tainted alike, and in the same time. But the animal body is not a dead soil in which bacteria can vegetate without disturbance. Though our blood and juices are the most perfect food the parasites require, though the animal temperature gives them the best conditions of life, they must still struggle for their existence with the cells of the animal body. We do not know yet in what way our tissues defend themselves, but that they do resist, and often successfully, is an inevitable conclusion. We can show this resistance experimentally in some cases. The ordinary putrefaction-bacteria can thrive excellently in dead blood, but if injected into the living blood-vessels they speedily perish. Disease-producing germs, however, are better adapted to the conditions they meet within the body they invade, and hence they can the longer battle with their host, even though they succumb in the end.

The resistance or want of resistance which the body opposes to its invaders is medically referred to as the predisposition to the disease. What the real conditions of this predisposition are, we do not know. Experience has simply shown that different individuals have not an equal power to cope with the parasites. Here, as throughout all nature, the battle ends with the survival of the fittest. The invaders, if they gain a foothold at all, soon secure an advantage by reason of their terrific rate of increase. In some instances they carry on the war by producing poisonous substances, in others they rob the animal cells of food and oxygen. If the organism can withstand these assaults, can keep up its nutrition during the long siege, can ultimately destroy its assailants, it wins the battle. Fortunately for us, victory for once means victory forever, at least in many cases. Most contagious diseases attack an individual but once in his lifetime. The nature of this lucky immunity is unknown. The popular notion, that the disease has taken an alleged “poison” out of the body, has just as little substantial basis as the contrary assumption that the parasites have left in the body a substance destructive to themselves. It is not likely, indeed, that an explanation will ever be given on a purely chemical basis, but in what way the cells have been altered so as to baffle their assailants in a second attempt at invasion is as yet a matter of speculation. Unfortunately for us, there are other diseases of probable bacterial origin, which do not protect against, but directly invite, future attacks.

A question now much agitated is whether each kind of disease germs amounts to a distinct and separate species, or whether the parasite of one disease can be so changed as to produce other affections as well. When investigations on bacteria were first begun, it was taken for granted that all bacterial forms, yeast cells, and mold fungus, were but different stages of one and the same plant. This view has long since been recognized as false. But even yet some botanists claim that all bacteria are but one species, appearing under different forms according to their surroundings, and that these forms are mutually convertible. The question is a difficult one to answer, since bacteria of widely differing powers may resemble each other in form. Hence, if a species cultivated in a flask be contaminated by other germs accidentally introduced, which is very likely to happen, the gravest errors may arise. But the more our methods gain in precision, and the more positive our experience becomes, the more do we drift toward the view that each variety of bacteria represents a species as distinct and characteristic as the separate species among the higher animals. From a medical standpoint this view, indeed, is the only acceptable one.

A disease remains the same in essence, no matter whom it attacks or what its severity be in the individual case. Each contagious disease breeds only its own kind, and no other. When we experiment with an isolated disease-producing germ, it causes, always, one and the same affection, if it takes bold at all.

But evidence is beginning to accumulate that, though we can not change one species into another, we can modify the power and activity, in short, the virulence, of parasites. Pasteur has shown that when the bacteria of chicken cholera are kept in an open vessel, exposed to the air for many months, their power to struggle with the animal cells is gradually enfeebled. Taken at any stage during their decline of virulence, and placed in a fresh soil in which they can grow, be it in the body of an animal or outside, they multiply as before. But the new breed has only the modified virulence of its parents, and transmits the same to its progeny. Though the form of the parasite has been unaltered, its physiological activity has been modified: it produces no longer the fatal form of chicken cholera, but only a light attack, from which the animal recovers. By further enfeeblement of the parasite, the disease it gives to its host can be reduced in severity to almost any extent. These mild attacks, however, protect the animal against repetitions. By passing through the modified disease, the chicken obtains immunity from the fatal form. In the words of Pasteur, the parasite can be transformed into a “ vaccine virus” by cultivation under conditions which enfeeble its power. The splendid view is thus opened to us of vaccinating, some day, against all diseases―in which one attack grants immunity against another. Pasteur has succeeded in the same way in another disease of much greater importance, namely, splenic fever.  The parasite of this affection has also been modified by him, by special modes of cultivation, so as to produce a mild attack, protecting against the graver form of the disease. Pasteur’s own accounts of his results, in vaccinating, against anthrax, the stock on French farms, are dazzling.  But a repetition of bis experiments in other countries, by his own assistants, has been less conclusive. In Hungary the immunity obtained by vaccination was not absolute, while the protective vaccination itself destroyed some fourteen percent of the herds.

Yet, though much of the enthusiasm generated by Pasteur’s researches may proceed further than the facts warrant, he has at least opened a new path which promises to lead to results of the highest importance to mankind.

The ideal treatment of any parasitic disease would be to administer drugs which have a specific destructive influence upon the parasites, but spare their host, i.e., the cells of the animal body. But no substance of such virtue is known to us. All so-called antiseptics, i.e., chemicals arresting bacterial life, injure the body as much as if not more than the bacteria. For the latter of all living beings are characterized by their resistance to poisons. Some attempts, indeed, have been made to cure bacterial (if not all) diseases by the internal use of carbolic acid, but they display such innocent naivete as not to merit serious consideration. More promising than this search after a new philosopher’s stone is the hope of arresting bacterial invasion of the human body by rendering the conditions unsuitable for the development of the germs, and thus affording the organism a better chance to struggle with them. Let me illustrate this by an instance described by Pasteur. The chicken is almost proof against splenic fever. This protection Pasteur attributes to the high normal temperature of that animal, viz., 42° Cent. At that degree of warmth the anthrax-bacillus can yet develop, but it is enfeebled. The cells of the bird’s body, thriving best at their own temperature, can hence overcome the enfeebled invader. Reduction of the animal’s temperature, however, by means of cold baths, makes it succumb to the disease, though recovery will occur if the normal temperature be restored in due time. In the treatment of human diseases, we have not yet realized any practice of that nature, but research in that direction is steadily continuing.

The most direct outcome of the germ theory, as far as immediate benefits are concerned, is our ability to act more intelligently in limiting the spread of contagious diseases. Knowing the nature of the poison emanated by such patients, and studying the mode of its distribution through nature, we can prevent it from reaching others, and thus spare them the personal struggle with the parasite. In no instance has the benefit derived from a knowledge of the germ theory been more brilliantly exemplified than in the principles of antiseptic surgery inaugurated by Lister. This benefactor of mankind recognized that the great disturbing influence in the healing of wounds is the admission of germs. It had been well known, prior to this day, that wounds heal kindly if undisturbed, and that the fever and other dangers to life are an accidental, not an inevitable, consequence of wounds. But Lister was the first to point out that these accidents were due to the entrance of germs into the wound, and that this dangerous complication could be prevented. By excluding the parasites from the wound, the surgeon spares his patient the unnecessary and risky struggle, giving the wound the chance to heal in the most perfect manner. Only he who has compared the uncertainty of the surgery prior to the antiseptic period, and the misery it was incompetent to prevent, with the ideal results of the modern surgeon, can appreciate what the world owes to Mr. Lister. The amount of suffering avoided and the number of lives annually saved by antiseptic surgery constitute the first practical gain derived from the application of the germ theory in medicine.

The cover of Popular Science containing the September 1993 article on germ theory.

Some text has been edited to match contemporary standards and style.