Preparadigmatic immunology

Protoimmunology: from the ancients to the Enlightenment

The scourges of infectious diseases have declined steadily and dramatically during the last century.

During this period, modern immunology had its beginnings and immunologists, not surprisingly, tend to see a causal relation between these events. But the discipline of public health was developed before immunology and has almost certainly played a larger role in the control of infectious disease and the elevation of the lot of humankind. It can be argued that the concepts and practices of public health raised the standard of living to the point at which individuals, now aware of the value of their own lives, wanted prevention of specific diseases (see Latour, The Pasteurization of France).

The fact that survivors of a plague were somehow spared from dire consequences of a second encounter with the disease was well known to the ancients. Thucydides, commenting on the plague of Athens of 430 bc: 'Yet stili the ones who felt most pity for the sick and the dying were those who had had the plague themselves and had recovered from it. They knew what it was like and at the same time felt themselves to be safe, for no one caught the disease twice, or, if he did, the second attack was never fatal. Such people were congratulated on all sides, and they themselves were so elated at the time of their recovery that they fondly imagined that they could never die of any other disease in the future.' (Thucydides, The Peloponnesian War).

The realization that the survivors of a plague having once recovered were not going to succumb to it in the future came not from experiment but from observation, as did so much understanding of the world. So, too, must have come the eventual realization that these survivors were not to be spared from other diseases in the future. But the idea of specific immunity to a specific disease was probably not yet understood. Many examples from antiquity through medieval times suggest that people were aware that they could protect themselves from disease. This 'protoimmunology', the nonscientific awareness that there could be protection to a disease, does not however seem to have played an important part in magic or religious ritual in early societies. Perhaps life was so fraught with danger from diseases of all kinds that freedom from one offered only a small respite. Another disease could strike soon; women risked dying in childbirth, men in war, and both by famine. The souls represented in a Breughel painting were not likely to have been aware of the subtle differences between one form of suffering and another. A few diseases like the black plague, smallpox and erysipelas had sufficiently distinct symptoms to stand out, but the inhabitants of early modern Europe could not distinguish easily the various forms of fevers and pestilence. Since the reason for the existence of these fevers and pestilence, often tied to magic and religion, was thought to be Divine retribution for collective sin, many people may have concluded that this suffering was not to be alleviated.

But if 'protoimmunology' was not part of ritual, it was a part of ordinary life in some societies. The Chinese inoculated healthy people with material removed from a pustule of a person with smallpox. They 'opened the pustules of one who has the Small Pox ripe upon them and drying up the Matter with a little Cotton .. . and afterwards put it up the nostrils of thowse they would infect . ..'. Smallpox was probably introduced into Europe by both the Crusaders and the Saracens in the sixth century. It is estimated that in sixteenth-century England, only five of 1000 persons escaped infection and over half of the population had obvious pockmarks. Smallpox was not as common by the eighteenth century, but it was still a real scourge for many people. Nevertheless, it was known in that century in some circles in England that people who had been infected with cowpox did not have the pockmarks of smallpox. Edward Jenner (1749-1823), who himself had had a traumatic experience when he had been treated with pustule material as a boy, turned this bit of folklore into what perhaps became the most famous clinical trial of all time. When he suggested to a Gloucestershire milkmaid patient that she had smallpox she replied, 'I cannot take the smallpox because I had had the cowpox.' Following her lead, in May of 1796, he inoculated 8-year-old James Phipps with cowpox and then, several months later, inoculated him with smallpox. James Phipps survived and the era of safe immunization began. Jenner's paper, which was rejected by the Royal Society ('lest he damage his reputation') and published privately, made him an international hero and opened the way for people to begin to think about prevention of specific diseases.

This advance coincided with the period we term the Enlightenment: public health had made life more 'civilized' and Europeans had come to believe in the goodness and perfectibility of human beings.

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