Lost in Translation? Cortisone and the Treatment of Rheumatoid Arthritis in Britain, 1950-1960. [corrected].

Cortisone, initially known as 'compound E' was the medical sensation of the late 1940s and early 1950s. As early as April 1949, only a week after Philip Hench and colleagues first described the potential of 'compound E' at a Mayo Clinic seminar, the New York Times reported the drug's promise as a 'modern miracle' in the treatment of rheumatoid arthritis (RA). Given its high profile, it is unsurprising that historians of medicine have been attracted to study the innovation of cortisone. It arrived at the end of a decade of 'therapeutic revolutions', kicked off by penicillin transforming the treatment of bacterial infections and ending with hopes of a revolution in the treatment of non-infectious, chronic inflammatory diseases. Despite these studies of cortisone's introduction, few historians have taken the story forward and considered how cortisone was adopted and adapted into clinical practice. This article tells the longer of how the drug and its derivatives were taken from research laboratories and integrated into clinical practice; what has in recent decades become known as translational medicine (TM). In exploring cortisone's first decade in Britain, we focus specifically on its role in the treatment of RA. Our approach is always to consider cortisone's use in the context of other treatments available to clinicians, and at local and national institutional settings. We do not discuss the many other therapeutic uses of cortisone, which ranged for topical applications for skin diseases to the management of cancers, especially childhood leukaemia, nor do we discuss its close analogue ACTH-AdenoCorticoTropic Hormone. We think there are lessons in our study for TM policies today.

The 70th anniversary of glucocorticoids in rheumatic diseases: the second youth of an old friend.

Seventy years ago, the first administration of cortisone in a patient with RA marked a milestone in the treatment of inflammatory diseases. However, the initial enthusiasm rapidly vanished as the administration of high doses for lengthy periods revealed worrisome adverse effects. It has taken several decades to overcome the (sometimes excessive) mistrust and to achieve a more differentiated evaluation of the benefit-risk profile and the adequate usage of glucocorticoids (GCs). Today, GCs remain indispensable for the treatment of many inflammatory conditions and their usefulness in RA as a disease-modifying low-dose co-medication is widely acknowledged. Recent studies show promising results concerning both traditional GCs and new formulations. Still, decades of relatively little scientific attention have resulted in a continuing lack of detailed evidence. Hence there is an ongoing need for further research regarding mechanisms of GC actions, the further optimization of treatment parameters for traditional GCs and new formulations.

The History of Cortisone Discovery and Development.

Philip Hench, Edward Kendall, and Tadeus Reichstein received the Nobel Prize in medicine and physiology in 1950 for their "investigations of the hormones of the adrenal cortex." Hench and Kendall took compound E from the laboratory to the clinic to the Nobel Prize in a span of 2 years. This article examines the paths that led to the day when the first rheumatoid arthritis patient received cortisone, and from there to the 1950 Nobel Prize ceremony. The aftermath of this achievement is also discussed. Although there have been significant advances in corticosteroid preparations and use since 1950, the side effects remain daunting.

Some social aspects of discovery, synthesis and production of cortisone in the 1930s-1950s.

A discovery, synthesis and therapeutic application of cortisone present a paradigm for modern translational medicine (Hillier 2007, Saenger 2010), since they represented a joint achievement of discoveries by biochemists, Edward Calvin Kendall and Tadeus Reichstein; large scale synthesis by an industrial chemist, Lewis Hastings Sarett, and therapeutic application by a rheumatologist, Philip Showalter Hench. The goal of translational medicine is to speed up the process between basic research and clinical practice, and to integrate multiple disciplines in order to understand diverse outcomes (Zhang et al. 2014). In this paper conditions that made this basic/applied/clinical research interface possible will be presented: the rise of steroid chemistry, simultaneous individual accomplishments as well as continuous cooperation among scientists, military competitiveness, and cooperation among pharmaceutical companies.

Compound f: the history of hydrocortisone and hand surgery.

Hydrocortisone (cortisol) is used daily in the practice of medicine and hand surgery. It has an effective use in a number of orthopedic conditions, including tendinitis, tenovaginitis, bursitis, carpal tunnel syndrome, and joint inflammation. But are surgeons aware of how this important pharmaceutical agent was discovered and prepared for clinical trial and who was responsible for its first clinical application? How did medical doctors determine that, like penicillin, cortisone and its derivative hydrocortisone would have such a life-changing effect on certain medical conditions? The purpose of this review is to relate the story of the development of cortisone (Compound E) and hydrocortisone (Compound F) and how both influenced the practice of hand surgeons in the treatment of rheumatoid arthritis and related inflammatory conditions. This history of cortisone and hydrocortisone also relates to the importance of partnership between physician and research scientist and of the principle at Mayo Clinic that the only concern--or the first concern--is the concern for the patient.

[History of corticotherapy]. / Histoire de la corticothérapie.

Corticosteroids emerged in the late 1940s, at a time when steroid chemistry began to offer new therapeutic approaches. Extractive chemistry (T. Reichstein), chemical synthesis (E.C. Kendall) and clinical investigations (P. Hench) were combined to result in the discovery of cortisone in 1948, leading to a long series of related derivatives. Besides their first applications to treat Addison's disease and rheumatic or inflammatory diseases, corticosteroids could easily correct many metabolic and functional symptoms. Fluoridation of the steroid skeleton allowed the development of more active and better tolerated molecules. Corticosteroids have revolutionized the treatment of allergic diseases or immunity troubles, graft rejection, many dermatological, respiratory, digestive, eye diseases, etc. It is used today in all areas of therapeutic.

[Stress, cortisone and homeostasis. Adrenal cortex hormones and physiological equilibrium, 1936-1960]. / Stress, Cortison und Homöostase. Kunstliche Nebennierenrindenhormone und physiologisches Gleichgewicht, 1936-1960.

This article investigates the emergence of the concept of stress in the 1930s and outlines its changing disciplinary and conceptual frames up until 1960. Originally stress was a physiological concept applied to the hormonal regulation of the body under stressful conditions. Correlated closely with chemical research into corticosteroids for more than a decade, the stress concept finally became a topic in cognitive psychology. One reason for this shift of the concept to another discipline was the fact that the hormones previously linked to the stress concept were successfully transferred from laboratory to medical practice and adopted by disciplines such as rheumatology and dermatology. Thus the stress concept was dissociated from its hormonal context and became a handy formula that allowed postindustrial society to conceive of stress as a matter of individual concern. From a physiological phenomenon stress turned into an object of psychological discourse and individual coping strategies.

Tadeusz Reichstein: from description of coffee aroma to discoveries of cortisone and aldosterone.

Tadeusz Reichstein was born in Wloclawek (Poland) into a Polish-Jewish family. His family emigrated to Switzerland, and he was educated in the Technical University of Zurich, becoming an engineer of chemistry. Thus he started his scientific career, firstly in Zurich and later in Basel. In his very busy life, he developed a method of vitamin C synthesis enabling industrial production of this important compound. Later, Reichstein isolated and synthesized such important adrenocortical hormones as cortisone, desoxycorticosterone and aldosterone. He received several awards but the most important was a Nobel Prize in Physiology or Medicine (1950). Reichstein spent the last years of his life in his own botanical garden and laboratory working on fern cytogenetics and the relations between different species of this archaic plant. Despite extraordinary and still valuable scientific achievements, he was always a very modest man with a humanistic attitude.

[Sympathetic ophthalmia, enigmatic malady]. / Ophtalmie sympathique, maladie énigmatique.

Sympathetic ophthalmia was a well-known but greatly feared entity in the 19th and most of the 20th century. This article reviews the Canadian medical literature, tracing the prophylactic and therapeutic modalities offered to treat this blinding affliction.

[Wars in the history of rheumatology]. / Le guerre nella storia della reumatologia.

Some important discoveries in the history of rheumatology happened during war periods. It is well known that arthritis associated with conjunctivitis and urethritis, following dysenteric episodes, has been described during the First World War from the German Hans Reiter and, nearly contemporarily, from the French Nöel Fiessinger and Edgar Leroy. Less known is instead the fact that the first cases of sympathetic algoneurodystrophy have been reported by the American Silas Weir Mitchell in soldiers wounded by fire-arms, during the Civil War of Secession. Other war episodes have been crucial for the development of some drugs now abundantly applied to the care of rheumatic diseases. The discovery of therapeutic effects of immunosuppressive agents, in fact, happened as an indirect consequence of the use of poison gas, already during the First World War (mustard gas), but above all after an episode in the port of Bari in 1943, where an American cargo boat was sunk. It had been loaded with a quantity of cylinders containing a nitrogenous mustard, whose diffusion in the environment provoked more than 80 deaths owing to bone marrow aplasia.Moreover, the history of the cortisone shows a strict link to the Second World War, when Germany imported large quantities of bovine adrenal glands from Argentina, with the purpose of producing some gland extracts for the Luftwaffe aviators, in order to increase their performance ability.