Teams

Team 1 : Antibiotics

Manager: Flurin Condrau

Communicable diseases continue to play an immense role as leading causes of death in today's world, and antibiotics remain the therapeutic agents of choice against such diverse diseases as tuberculosis, stomach ulcers caused by Helicobacter pylori or Staphylococcal infections. A report by the business information service Report Buyer estimates that the global market for antibiotics will reach 25 billion US dollars by 2010. Six specific antibiotics have achieved annual sales valued at more than 1 billion US dollars each, and increased problems with drug resistant disease agents drive the research and development of new antibiotics as existing medications loose their efficacy. This cycle of innovation, rapid clinical application and the development of resistance is a characteristic of antibiotics that has started to attract the attention of historians. Members of our team have investigated changes in the hospital environment as well as international comparative perspectives on resistance and policy responses. With the emergence of MRSA and a wide spectrum of hospital based, so called nosocomial infections, the relationship between antibiotics, the hospital environment, and medical intervention has become somewhat problematic, and further research on this is required.
Part of the market success of antibiotics lies in their importance for out-patient primary care. Recent research published in the Lancet suggests that in France, 32.5 defined daily doses of antibiotics per 1000 population were prescribed in out-patient general practice, as opposed to 10.0 such doses prescribed in the Netherlands between 1997 and 2002. This points in part to cultural differences within Europe regarding acceptable levels of drug prescription, but it also reflects the commodification of antibiotics and their framing as 'Magic Bullets' within localised contexts. Antibiotics have certainly led the way when it came to popular as well as clinical reputation and can in many ways be seen as the proverbial Magic Bullets. This has strong implications for the history of disease management and general practice and will require careful further analysis.
The history of antibiotics and the development of randomised clinical control trials are strongly intertwined. The first such trial, to assess the effectiveness of Streptomycin against tuberculosis, achieved two separate aims: it irreversibly established a new standard regime for assessing drug safety and efficacy whilst at the same time proving that one of the major killers of the twentieth century could be successfully controlled with antibiotics. The repercussions have been immense, and the history of clinical trials regimes as well as the new found emphasis on evidence based medicine are yet to be fully investigated by historians.

Team 2: Chronic Illnesses

Manager: Carsten Timmermann

Cardiovascular disease today is a leading cause of death, and cardiovascular drugs are a big business. A report by the business information service Espicom values the global market for medicines used in the management of blood pressure and cholesterol levels at around 38.5 and 34 billion US dollars respectively. A significant proportion of this money is spent on a small number of blockbuster drugs. In most cases these medicines are taken by patients whose high blood pressure or cholesterol levels do not cause them any direct suffering. They are not 'magic bullets', but are taken over long periods of time to reduce the long-term risk of strokes or heart attacks. These drugs have become part of normal everyday life for many in the developed world. But medicines that treat risks must not in themselves pose a risk. Since pharmaceuticals never come without side effects, and because of their high sales, which make even the rarest side effects visible, the development of these drugs can be risky for pharmaceutical companies, as the example of Bayer's anti-cholesterol drug Lipobay has shown. Members of Team 2 have worked on the history of the transformation of cardiovascular drugs into blockbuster medicines, which took place in Western pharmaceutical research, development and marketing after World War Two. The team will pursue this work, examining how taking such powerful (and often expensive) drugs regularly and over long stretches of time it has become 'normal'.
Cardiovascular drugs have become some of the most therapeutically effective and commercially successful drugs of the twentieth century, and many of them have rich histories. Plant extracts, the best known of which is digitalis, have long been used to treat 'heart weakness'. They serve as examples for the classic story of drug invention, from the observation of the effects of a plant, via the purification of its active substances in the laboratory and the analysis of their structure and function, to the synthesis of this active principle. As for other biologicals, in order to use these plant substances as medicines, standardizing their effects is essential, and the principles and processes of 'Wertbestimmung', as proposed by Paul Ehrlich, are central to this enterprise. The team will also study the commercial exploitation of such plant extracts, active principles, and synthetic products. Other natural compounds such as the arrow poison curare were long used by physiologists as research tools. For decades they had no clinical uses, until the epidemiological transition of the mid twentieth century in Europe and North America made the development of drugs for cardiovascular disorders an increasingly high priority. Curare was thought to be useful in anaesthesia, but the identification of its active principle also led to the observation that synthetic analogues lowered the blood pressure of laboratory animals. The team will study the ways in which natural and synthetic drugs travelled from the physiological laboratory into the clinic. Standardization in this context involved not only laboratory techniques, but also the development of new clinical approaches, the education of doctors, nurses and patients, the gathering of large sample populations in order to collect statistical data and test compounds, the use of new monitoring technology, and in some cases the creation of new disease entities.

Team 3: Biological drugs

Manager: Alexander von Schwerin

Biotechnology today is often portrayed as a radically new era of innovation, playing a central role in the transformation of industrial and medical practices. Biological drugs have however a long history illustrative of the changing relations between biological laboratories, clinical services, industrial settings, and regulatory bodies. Recent discussions about the widespread use of oestrogen replacement therapy in post-menopausal women, the balance of their effects (reducing the risk of osteoporosis on the one hand, increasing the risk of breast cancer on the other hand) illustrate the potency as well as the dangers of these drugs, their massive consumption, as well as the various - and occasionally conflicting - interests involved in their production, circulation, and evaluation. There is a rich history of such configurations.
While many pharmaceuticals of the 19th century were preparations made out of plant and animal bodies, the industrialization of drug making in the 20th century has resulted in the appearance of new classes of biological drugs ranging from vaccine and sera to vitamins and hormones. These new active substances posed specific scientific, industrial, medical and legal problems that make them especially interesting for understanding the therapeutic revolution and its relations to standardization. The new biologicals were seen as the best examples of what bacteriological or biochemical research could contribute to medicine. Characterized as pure and natural substances, they were taken as extremely potent physiological modulators acting in a specific way and in very small quantities. The diversity of their effects and side effects however challenged the clear-cut definition of dosage and indications essential to the aims of pharmacological and clinical standardization. Biological drugs were also extracted, produced and commercialized long before one could characterize them at the molecular level. As a consequence of both the variability of the biological raw material and of the uncertainties regarding the composition of extracts, standardization was equated with the conduction of biological assays. Up to the present these assays have been major targets of industrial as well as administrative forms of regulation and standardization. One final issue for which the trajectory of hormones and biological drugs is highly revealing is the question of appropriation and market construction. It is often forgotten that in most European countries therapeutic agents were not patentable. As they were not included in the traditional pharmacopoeia, biological drugs were the pharmaceutical "terrain" upon which several forms of patenting and intellectual property protection that became dominant in the late 20th century were experimented.
Biological drugs will therefore serve as key examples in the history of standardization in production, in state administration and patent offices, as well as the bedside.

Team 4: Psychochemicals

Manager: Magaly Tornay

The ways of experimental development, production, search for indications, clinical trials, implementation, regulation of drugs and their various effects on clinical-scientific as well as socio-cultural contexts are currently the focus of intense historical research in countries such as Switzerland, Germany, the Netherlands, Belgium and Denmark. Under the roof of the ESF RNP network on DRUGS, researchers have been allied in a European-wide working group on psychochemicals. Over the last fifty years, health care systems in European countries have become increasingly dependent on industrially produced psychopharmaceuticals, whose implementation has led to a deep transformation in psychiatry and the mental health sector in general. The introduction of the first neuroleptics and tranquilizers had a deep impact on therapeutic practices as well as on daily life in mental health facilities. This did not only lead to the elimination of straitjackets and the old somatic treatments, but also gave way to a diversification of psychiatric institutions and to more ambulant and flexible treatment for mental health problems. In response to the effects of psychochemicals, diagnostic categories and the perception and conception of 'madness' changed and were scientifically standardized.
Among the many drugs that are present in modern medicine and in our daily life, psychochemicals have a special status. Similar to other substances, patients and psychiatric practitioners see in them the power to relieve suffering and to cure, or at least manage, disease. But psychochemicals are an even more potent category, since they seem to be aiming at the 'psyche' or 'mind' and have the ability to moderate our mood and our conduct. They are therefore strongly entangled with hopes, but also with fears: A widespread unease towards modern medicine and the strategies of pharmaceutical companies as well as exorbitant expectations for enhancement and self-modulation are often associated with psychoactive drugs.
Psychochemicals stand at the centre of complex networks that bind together various actors and social fields, such as the pharmaceutical companies who produce them, the psychiatrists or doctors who prescribe them, as well as the patients who consume them. Members of the Team 4 aim at studying different 'drug trajectories' through these networks and their historical contingencies. Therefore, an interdisciplinary and comparative approach that seeks for more thorough exchanges between the history of science and technology, (social) history of medicine, social-cultural history, and the history of economy is key to the psychochemical group.