History of Allergy and Immunology

Making immunity an experimental subject

Immunology developed around a difficult question: why does exposure to disease sometimes produce protection, while apparently similar exposures have different consequences? Its history connects laboratory experiments with attempts to prevent and treat infection. The related history of vaccination provides one route into that larger story.

By the beginning of the twentieth century, serum therapy offered another approach. In his 1901 Nobel lecture, Emil von Behring described blood-derived substances capable of counteracting diphtheria toxin. Protection could therefore be investigated through the interaction of a particular toxin and an antitoxic serum. His account illustrates the growing importance of experimental specificity: the effect depended on what the serum acted against. These historical experiments explain the development of a research programme; their procedures are not instructions for medical treatment. Behring’s Nobel lecture

Cells, circulating substances and competing explanations

Early immunology contained substantial disagreements about how protection worked. Cellular explanations emphasized the activity of living cells, particularly the engulfment of foreign material by phagocytes. Humoral explanations emphasized protective substances in bodily fluids. These approaches involved different experimental traditions and different ways of imagining the body’s response to infection.

Ilya Mechnikov’s 1908 Nobel lecture situated his work within that dispute and connected investigations of digestion in comparatively simple organisms with the study of immunity. His shared award with Paul Ehrlich marks the historical importance of both research traditions. It should not be read as evidence that all their theoretical differences had disappeared. The 1908 Nobel award is a useful landmark in the formation of the discipline, rather than a single moment when its problems were solved. Mechnikov’s Nobel lecture

When exposure increased susceptibility

Anaphylaxis challenged any simple equation between previous exposure and increased protection. Charles Richet’s retrospective account described experiments in which an animal previously given an injection became much more susceptible to a subsequent exposure. By 1902, he and his collaborators had identified features of this response, including an interval between exposures and a striking difference between the first and subsequent reactions.

The historical significance lies in the reversal of expectation: an encounter could prepare an organism for injury as well as resistance. Richet’s 1913 Nobel lecture is valuable evidence for how a participant explained that discovery. Its descriptions of symptoms, timing and mechanism belong to particular experiments and to the concepts available to him. They should not be treated as universal modern diagnostic criteria for anaphylaxis. Richet’s Nobel lecture

The changing meaning of allergy

In 1906, the Viennese paediatrician Clemens von Pirquet introduced the term allergy. His meaning was broader than its familiar later use. He sought to describe altered responsiveness, including changes in the timing, strength and character of a reaction. Both increased and decreased sensitivity could fall within this framework.

This distinction matters when reading historical records. A reference to allergy in Pirquet’s work cannot automatically be translated into a present-day diagnosis of allergic disease. His attention extended beyond an external substance to the condition and responsiveness of the organism encountering it. Historian Benedikt Huber’s examination of Pirquet’s writings emphasizes this broader conception. Allergy’s history consequently involves changes in language and disease classification as well as discoveries in laboratories. Naming the phenomenon helped organize questions, but the name itself did not establish a single mechanism. Huber’s study of Pirquet

Tolerance and the boundaries of immune response

Research on transplantation brought a complementary problem into focus: why might foreign tissue sometimes be accepted instead of rejected? Peter Medawar’s investigations connected tissue transplantation with experimentally acquired tolerance. The 1960 Nobel Prize recognized Frank Macfarlane Burnet and Medawar for work on acquired immunological tolerance.

This development broadened the field’s central questions. Explaining immunity required attention not only to a response being generated, but also to circumstances in which a response did not occur. In historical perspective, tolerance and hypersensitivity exposed different limitations of an exclusively defensive picture of immunity. Their connection is conceptual rather than an assertion that they share one mechanism. The transplantation work established a distinct experimental problem with major implications for understanding how immune responsiveness develops. Medawar’s Nobel biography

IgE and the legacy of experimental allergy

During the 1960s, investigations associated with Kimishige and Teruko Ishizaka, and with Gunnar Johansson and Hans Bennich, helped establish IgE as a distinct class of immunoglobulin. This gave a molecular identity to activity previously investigated under the name reagin and connected important allergic reactions with a particular antibody class. The discovery emerged through converging investigations rather than an isolated observation. The discovery of IgE 50 years on

Taken together, these episodes support a history organized around changing questions: how protection could be transferred, how cells contributed to defence, why exposure could increase susceptibility, and how responsiveness could be absent or altered. This is a synthesis of the preceding evidence, not a claim that one discovery explains every immune disorder. Historical terms and experimental conclusions require interpretation in their original settings. The enduring contribution of allergy to immunology was to make harmful responsiveness a central problem alongside protection.