The decision to initiate invasive, first-in-human trials involving Parkinson’s disease presents a vexing ethical challenge. Such studies present significant surgical risks, and high degrees of uncertainty about intervention risks and biological effects. We argue that maintaining a favorable risk-benefit balance in such circumstances requires a higher than usual degree of confidence that protocols will lead to significant direct and/or social benefits. One critical way of promoting such confidence is through the application of stringent evidentiary standards for preclinical studies. We close with a series of recommendations for strengthening the internal and external validity of preclinical studies, reducing their tendency toward optimism and publication biases, and improving the knowledge base used to design and evaluate preclinical studies.

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America experienced a genuinely vast development of biomedical science in the early decades of the twentieth century, which in turn impacted the community of academic psychiatry and changed the way in which clinical and basic research approaches in psychiatry were conceptualized. This development was largely based on the restructuring of research universities in both of the USA and Canada following the influential report of Johns Hopkins-trained science administrator and politician Abraham Flexner (1866–1959). Flexner's report written in commission for the Carnegie Foundation for the Advancement of Teaching in Washington, DC, also had a major influence on complementary and alternative medicine (CAM) in psychiatry throughout the 20th century. This paper explores the lasting impact of Flexner's research published on modern medicine and particularly on what he interpreted as the various forms of health care and psychiatric treatment that appeared to compete with the paradigm of biomedicine. We will particularly draw attention to the serious effects of the closing of so many CAM-oriented hospitals, colleges, and medical teaching programs following to the publication of the Flexner Report in 1910.

The concept of neuronal plasticity is widely used, but seldom defined in the neurosciences. It can signify many different occurrences, such as structural alterations of axons and dendrites (Cotman & Nadler, 1978), behavioural adaptations (Rosenzweig & Bennett, 1996), or physiological changes in synapse formation (Martin et al., 2000) at different stages of health and disease. Although there is such a wealth of research from many disciplines, the neuroanatomical aspects of plasticity are the focus of this paper. It seeks to illuminate the evolution of different concepts of plasticity concerning the structure and circuitry of the central nervous system (CNS). Early modern morphological research on de- and regeneration phenomena in the 19th- and early 20th-century is well documented. These studies, however, almost exclusively concentrated on the peripheral nervous system (PNS). It was one of the major contributions of Santiago Ramón y Cajal (1852-1934), that he applied the concept of regenerative capacities to the CNS. But the term plasticity seemed to have disappeared for about two decades after his death. The ensuing comeback of the expression may be attributed, at least in part, to new neuroanatomical staining and tracing methods. The pursuit of these techniques will serve as a guidepost through varying approaches in different times: It was the 1950s which seemed to spawn the time for new departures in structural investigations of neuronal plasticity.

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