‘Trouble from within’: allergy, autoimmunity, and pathology in the first half of the twentieth century

Abstract

Traditionally, autoimmune disease has been considered to be a case of false recognition; the immune system mistakenly identifies ‘self’ tissues as foreign, attacking them thus causing damage and malady. Accordingly, the history of autoimmunity is usually told as part ot the history of immunology, that is, of theories and experiments relating to the ability of the immune system to discriminate between self and nonself. This paper challenges this view, claiming that the emergence of the notion of autoimmunity in the 1950s must be considered as part of a long develolpment in thought about pathology throughout the twentieth century, namely the conceptualisaiton of disease as a reactive and self-destructive process. During the first part of the twentieth century this notion became one of the cornerstones of pathology and was increasingly employed for the explanation of the non-infections, slow-burning diseases. Thus, the category of chronic disease had been defined anew, now encompassing all those diseases characterised by a persistent inflammatory process. Inflammation, in turn, was conceived as double-eged physiological mechanism, which was usually the direct mediator of damage, of the essence of disease. The paper also shows how this kind of analysis could emable a unified historical discussion of autoimmunity and allergy, hitherto considered to have distinct conceptual origins.

Introduction

According to current estimations, about twenty percent of the population suffer from one or another kind of autoimmune disease.¹ A long list of diseases formerly considered ‘degenerative’ are now regarded as, or least are highly suspected to be, of autoimmune aetiology: type I diabetes, rheumatoid arthritis (and its many derivatives), multiple sclerosis, inflammatory bowel disease (Crohn’s disease, ulcerative colitis), and systemic lupus erythromatosis. Recently, even AIDS and Alzheimer’s disease have been speculated to have autoimmune pathogenesis.²

But what is autoimmune disease? The prevailing answer is seemingly simple. According to the official definition of the National Health Institute (NIH): ‘If a person has an autoimmune disease, the immune system mistakenly attacks self, targeting the cells, tissues, and organs of a person’s own body’.³ Thus the body is damaged by ‘friendly fire’, as one author named it in a popular book on the subject.⁴ In multiple sclerosis, for example, the myelin layer (or ‘sheath’) enveloping the nerves is destroyed, causing nervous impairment and paralysis.⁵ At the heart of this view of autoimmune disease is the notion of the immune system as a mechanism of self–nonself recognition (SNS). Accordingly, the essential logic of the activity of the immune components is assumed to be always the distinction between ‘self’ tissues and everything that is not self (‘foreign’ or ‘nonself’). The immune system should be able to recognise an intruding pathogen and destroy it, or to identify a nonself transplanted tissue and reject it. At the same time, no immune reaction should be developed against any of the constituents of the body—this is called ‘immunological tolerance’. Assuming this model to be true, autoimmune disease represents a malfunction of the self–nonself discrimination mechanism of the body; a case of ‘breakage of tolerance’ as it is often described. As one of the founders of the discipline declared in 1965, ‘it should not happen but it does!’⁶

This view of autoimmunity has traditionally led to a particular history of this kind of disease, namely a history of those ideas, observations and experimentation which served to clarify the SNS characteristics of the immune system. Consequently, the history of autoimmunity has become an inseparable part of the history of the notion of self–nonself recognition, and of the theory of tolerance.⁷ From this perspective, autoimmunity was born in the 1950s as a product of the work of Macfarlane Burnet and Peter Medawar.⁸ Although observations of ‘auto-antibodies’ were reported since the beginning of the twentieth century, they were practically ignored or at least not seriously pursued.⁹ These were ‘the dark ages of autoimmunity’, as Arthur Silverstein termed them.¹⁰

The self–nonself paradigm was established in the 1950s, largely supported by new insights into the problem of tissue transplantation and rejection. Burnet and Medawar contended that self-tolerance was not due to genetic differences, but a result of a learning process taking place during embryonic development.¹¹ According to Burnet, the immune system was made of numerous ‘immunologically competent’ clones of cells (lymphocytes), circulating around the body in a constant surveillance for harmful invaders. Altogether, the repertoire of circulating lymphocytes should cover all of the conceivable array of intruding antigens. At the same time, no lymphocytes with specificity to any of the body’s tissues should be allowed to develop or exist in a normal individual. It was only through a genetic fault or an induced mutation that such a self-clone could appear again in adult life and bring about damage. Burnet called it ‘the forbidden clone theory’ of autoimmunity.¹²

In 1955, the first systematic observations of pathological autoimmune phenomena were also reported. Of seminal importance in this context was the work of Ernst Witebsky on tissue specificity. While conducting various experiments with Noel Rose he realized that under experimental conditions, rabbits are able to produce circulating antibodies against their own thyroid.¹³ Shortly afterwards, and with a loose relation to Witebsky and Rose’s work, a group of British investigators was able to show that very similar pathological lesions, including the anti-thyroid antibodies, could be demonstrated in some humans suffering from thyroiditis. Thus, this kind of inflammatory thyroiditis (lymphadenoid goitre, or ‘Hashimoto’s disease’) could be shown to be of an autoimmune nature.¹⁴ Within a few years, a whole series of diseases were shown to have a similar auto-immunologic component, thus giving birth to this new nosological category.¹⁵

In the following paper, I want to develop a new approach to the history of autoimmune diseases. As an alternative to the current understanding, I will put forward a twofold argument. Firstly, I claim that the histories of allergy and autoimmunity have to be considered as overlapping and largely interrelated. Traditionally, both allergy and autoimmunity have been considered as distinct ‘chapters’ in the history of immunology, having only occasional relations.¹⁶ Surprisingly enough, hardly any attention has hitherto been given to the mutual history of these two bodies of medical knowledge. Secondly, embarking on such a broad historical perspective, reaching back to the beginning of the twentieth century, allows me to trace the origins of autoimmune disease to far earlier than the 1950s.

Allergy, it is commonly assumed, was born in the first years of the twentieth century, and has gradually established itself ever since. Autoimmunity, on the other hand, is thought to have had its real beginnings only after the Second World War. Moreover, allergy is widely considered as a half-serious condition, affecting large segments of the population but inflicting ‘real’, life-threatening danger only on relatively few individuals. Autoimmunity, by contrast, is about real, hardcore diseases—diabetes, multiple sclerosis and so on—which as a rule cause severe impairment and often death. In the case of allergy it is the environmental, non-specific character of the reaction that is usually given consideration. In autoimmunity, it is the ‘mistaken’ attack of self-tissues that stands in the focus of debate. Challenging this sharp distinction between allergy and autoimmunity, and placing them together within a wider historical context, shows how deeply rooted they both were in the pathological thought developing in the first half of the twentieth century. As I will argue, medical research in the first decades of the century was focused largely on self-destructive, reactive processes in disease.¹⁷ The establishment of allergy, around 1910, was but one aspect of this development, which itself was constitutive of the development of the concept of chronic, inflammatory degenerations, which, in turn, preceded and conditioned the idea of autoimmune disease.

I shall begin by setting the stage for my argument at the dawn of the bacteriological revolution in the 1870s. The third part then explores the establishment of the concept of disease as self-destruction during the last decades of the nineteenth century. I then examine developments in pathology at the turn of the century, which I characterise as focused on the individuality and idiosyncrasy of disease. In the fifith part I discuss the interrelations between allergy, reactivity, and inflammation in the first decades of the twentieth century, followed by a discussion of a disease that I consider paradigmatic for this issue: rheumatoid arthritis. In the seventh part I argue that by the 1940s, the concept of chronic disease in terms of self-destructive, hyperreactive processes was largely complete. Thus, autoimmunity, established in the 1950s would be not much more then a further elaboration of a well-established pathological concept.

Both allergy and autoimmunity, I shall conclude, constitute paradigmatic examples of this new pathological imagery, with wide reaching consequences even for our current understanding of pathological process: disease as ‘trouble from within’.¹⁸