Horror autotoxicus, Autoimmunity, and Immunoregulation: The Early History

Abstract

For many years Paul Ehrlich’s theory of horror autotoxicus - that autoimmune disease could not occur - dominated 20th Century thinking. It inhibited acceptance of both clinical and experimental observations testifying to the reality of such a possibility. Then, for almost one halfcentury, immunology lost its medical foundation, and became primarily a chemically oriented discipline. Both of these factors prevented the asking of questions that would have pointed to the importance of immunoregulatory mechanisms in the immune response. Then a variety of biological and medical observations were made in the 1940s and 1950s that demanded a new approach to theory and to experiments. Led by Macfarlane Burnet, an immunobiological revolution took place that made the clarification of cellular and molecular regulatory mechanisms one of the central interests of the new immunobiology.

The flip side of immune surveillance: immune dependency

“…In some cases, as in smallpox and polio, the resistance induced is so profound that the disease can be completely eradicated within an immunized population. For many years it was believed, erroneously, that an immune reaction to a cancer was impossible, because cancer was part of the self and autoimmunity was necessarily forbidden: Ehrlich's doctrine of 'horror autotoxicus' (1). It is no wonder that it took many years for the contrary idea, that autoimmunity is commonplace, to be fully appreciated.…”

Autoimmune Reactions after Electro‐oxidation of IgG from Healthy Persons

“…Autoimmunity was recognized in the early works of Metalnikoff and others, who demonstrated the formation of autoantibodies more than a hundred years ago (historical review in Ref. 23). On the contrary, Ehrlich postulated autoimumunity as a nonexisting possibility—unwillingness of the organism to jeopardize itself by formation of autoantibodies (horror autotoxicus).…”

“…His opinion that autoimmune disease cannot occur dominated decades. The study of autoimmunity joined the mainstream of immunology in the sixties of the last century when Burnett and others introduced the biological aspect of immune response regulation and a concept of immunological tolerance 23 . Nowadays, we are confronted with statements that “everything is autoimmune until proven otherwise” as Shoenfeld made in the opening greetings at the 3rd Central European Congress of Rheumatology in 2000 24 .…”