[In the following essay, originally published in 1954, Shryock argues the importance of Cotton Mather's medical writing as the sole example of germ theory in eighteenth-century American writings.]

Little has been written about medicine as it existed in the English-American Colonies prior to about 1750. Yet European medicine was practiced in these Colonies for well over a century before that time. The reasons for this neglect of early Colonial medicine are obvious enough. American physicians of that period received no formal training, the profession was unorganized, and there were no such medical institutions as schools, libraries, or hospitals. The population was small; in 1720, for example, only four towns could boast of as many as 5,000 inhabitants. The few men who were at all learned in medicine were not the apprentice-trained physicians but were rather the generally well-educated government officials or clergymen. Even these men wrote little in the medical field, and that little was unpublished and of a fragmentary nature.

The chief exception to this rule is to be observed in the work of the Reverend Cotton Mather, a clergyman of the Calvinistic, State Church in Boston, Massachusetts. Mather was a prominent figure there during the years between about 1690 and 1725. He is usually remembered now for his theological and historical writings, but was also much concerned with medicine and at one time thought seriously of practicing as a physician. He was, moreover, interested in many aspects of contemporary science and became one of the few Colonial members of the Royal Society of London.

Mather's medical thought combined theological, occult, and scientific ideas in a way which seems bizarre today but which was not uncommon in the seventeenth century. He ascribed all disease, for example, to an ultimate source in original sin. Although much of his writing now appears archaic, he kept abreast of the latest scientific developments of his time. He may therefore be viewed as a transitional figure who simultaneously looked back to the Renaissance and Reformation and forward to the Aufklärung or Enlightenment. We are concerned here only with the forward-looking aspects of his medical thought.

Mather published a number of pamphlets on measles and on smallpox, sent reports on case histories and promising drugs to the Royal Society, and sought at times to advise the local physicians. But his chief work in this field was the completion, about 1725, of a general treatise on medicine entitled The Angel of Bethesda. This opus, although never published and subsequently ridiculed or forgotten, offers us the only such treatise prepared in the English Colonies prior to the American Revolution. It was in part a scientific work, in part a popular manual for family use (domestic medicine). Although crammed with moralizings and lists of meaningless drugs, it is of great interest in two respects. It is unique in American annals in providing an integration of theology and medicine, and it is also the only American study of the eighteenth century which presents the animalcular or “germ” theory of the origin of infections.

Mather derived this theory from the writings of Kircher, Lieuwenhoek, and Benjamin Marten of London. He made no attempt to verify it by direct observations, but accepted it as best explaining many epidemiologic phenomena. In this respect, he shared the views of various Europeans who were then interested in the animalcular hypothesis. Mather was unusual, however, in that he applied the hypothesis to a new field—to what would now be termed immunology. This application came about in the following manner.

Medicine appealed to Mather, not only as a science but also as a means for helping his fellow men. He was anxious, as a clergyman, to employ medicine for the welfare of his parishioners and of his entire community. He particularly desired to protect the public from the diseases which were then most feared, that is, from epidemics of measles, diphtheria, and smallpox. Hence he was much interested when, about 1715, a Negro slave told him about an African practice of inoculating men with smallpox “virus” as an immunizing procedure. This interest was heightened when, several years later, reports of a similar folk practice in the Near East appeared in the Transactions of the Royal Society. The clergyman then decided to urge the use of inoculations whenever smallpox again broke out in his city.

Smallpox epidemics occurred, almost simultaneously, in both London and Boston in 1721. In the former city, at the urging of Lady Montagu, some twenty persons were inoculated in the hope that they would suffer mild cases and be protected thereafter against infection. This well-known episode is usually said to mark the beginnings of inoculation in the Western world. What actually happened, however, was that one or two deaths occurred following these inoculations; hence there was much opposition and no extensive experimentation with the practice occurred in England that year.

In Boston, meantime, Mather appealed to the local physicians to employ the same procedure. All but one of these men refused, condemning inoculations as both dangerous and irreligious. But Mather persuaded one practitioner, Zabdiel Boylston, to undertake this work; and during the next five months Boylston inoculated nearly two hundred and fifty persons. This was apparently the first experiment with active immunization ever carried out on a significant scale in the Western world. Mather and Boylston reported to the Royal Society that the inoculated cases of smallpox were usually mild and that the mortality rate among them was—at the worst—not more than two percent. In contrast, the rate among cases acquired “in the natural way” was over fifteen percent.

These reports were contested in London as in Boston, but they became a part of the evidence which supported continued inoculations in England, and from that country the practice spread gradually to the Continent. By the later eighteenth century, it became widespread and was made much safer when Jenner modified it by using cowpox rather than smallpox virus (1798). Thus, the experiments instigated by Mather and carried out by Boylston were the beginning of a positive type of preventive medicine.

It is usually assumed that early inoculations were merely empirical procedures but this was not the whole story in Mather's case. Like several contemporary Europeans, he formulated theories in order to explain why the inoculated “virus” usually produced only a mild case and also conferred immunity thereafter.

The clergyman's explanation of the mild reactions was as follows. In “natural” infection, he held, the smallpox virus first gained access to the body through respiration. From the lungs, the “virus” was then carried directly by the blood to the surrounding organs, where it did immediate, major damage. Serious illness ensued. But when the virus was introduced by inoculation, it was injected into a limb distant from these organs. It then had to make its way to the central parts of the body, and in the process was resisted by the blood or solid structures. Hence, by the time the “virus” reached the heart, lungs, and so on, it was weakened, or, as we would now say, attenuated. Only a mild illness then followed.

Mather thus assumed that mild reactions following inoculation could be explained entirely by what happened after the virus entered the body. His theory was vague but plausible, and it can be reconciled, at least in a general way, with modern views of the varying susceptibility of different body parts and also with present concepts of the role of the blood in resisting infections. Few contemporaries even envisaged the problem with which he was concerned. There were, however, several European physicians who also pondered the matter and they suggested another theory; namely, that the virus was weakened in some way before it was injected in inoculations. This also could, in theory, account for the mild reactions.

Mather went further than most of these early immunologists, meantime, in employing the animalcular hypothesis at this point. The virus used in the inoculations, he held, was probably composed of pathogenic microorganisms. He declared indeed, that it was this theory which led him to ponder the problems of infection in the first place. As he put it, this “germ” theory drew him “into new Sentiments about the way of its (smallpox's) Conveyance, and the Cause why tis conveyed but once.”

The animalcular theory then led Mather into further speculations on the second problem which he here mentions; that is, on how inoculations produced subsequent immunity. His exact words were:

The Enemy (the living “virus”) 'tis true, gets in so far (into the body) as to make some Spoil; even so much as to satisfy him, and leave no prey in the Body of the Patient, for him ever afterwards to seize upon … the vital Powers are (therefore) sure of never being troubled with him anymore.

The use here of such words as “enemy” and “prey” was probably suggested by the assumption that the “virus” was indeed composed of living invaders. The meaning of the statement may have been that the “virus,” once present in any part of the body, consumed all that was useful to it. Then, if a similar “virus” invaded the body at a later time, it found no appropriate substance remaining and could not survive. Hence one attack of the disease conferred lasting immunity.

Such speculation now seems a bit fanciful. More pertinent to modern concepts was Mather's realization that the animalcular theory held out great possibilities for chemotherapy. Drugs which could kill the pathogenic animalculae would be far more effective, he declared, than any remedies then in use. The animalculae must be entirely eliminated: otherwise, the few remaining ones would multiply and so continue the disease process. But Mather noted that such chemotherapeutic agents as were then available (notably mercury) were highly dangerous to patients as well as to microorganisms. The implication was that new and safer drugs must be found. Since Mather believed that different species of organisms would produce different diseases, one may also see here an inplication that the drugs needed would have to be of a more or less specific nature. But Mather made no specific statement to that effect.

It is surprising that a provincial clergyman should have envisaged both the promise and the difficulties of chemotherapy as early as 1725. But there is no evidence that his suggestions on this subject exerted any influence on contemporary medicine. Mather's enduring contribution was therefore not made in the field of therapy, but rather in that of preventive medicine.

In playing a part in introducing active immunizations into American and European practice, Mather helped to inaugurate a significant trend in later medicine. Inoculations against smallpox not only led into Jenner's work on vaccination, (which was simply inoculation with a safer virus) but also prompted inoculating experiments with such other diseases as syphilis, measles, and tuberculosis during the century between 1775 and 1875. After the latter date, as is well known, Pasteur and others finally established active immunizations on the same rational, bacteriologic basis as Mather had earlier postulated. It would seem, therefore, that the Boston clergyman deserves a place in the history of Western medicine as a whole.