Optimal Linear Estimation (OLE) Modeling Supports Early Holocene (9000–8000 RCYBP) Copper Tool Production in North America

The discovery and development of metal as a tool medium is a topic of global interest. A fundamental research goal involves establishing the timing of human experimentation with naturally occurring copper ore, which is commonly associated with sedentary, agrarian-based societies. However, in North America, there is well-documented millennia-scale exploitation of copper as tool media by small, seasonally mobile hunter-gatherer groups in the western Great Lakes. Archaeologists have suggested that Late Paleoindian groups may have begun using copper as a tool medium almost immediately after they entered the Lake Superior basin. However, only a few radiocarbon dates support such early use of copper. Here, we use optimal linear estimation modeling to infer the origin date for copper tool production in North America. Our results show that the invention of copper as a tool media likely occurred shortly after the first pioneering populations encountered copper ore during the Pleistocene-Holocene transition. The origin dates modeled here (ca. 8100 RCYBP) reveal several important features about the behavior of pioneering hunter-gatherer populations. Moreover, our results suggest that this phenomenon represents the earliest known use of metal for utilitarian copper tool production.

The attitude of patients with progressive ataxias towards clinical trials

Background The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status. Results Of 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration. Conclusions Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.

DISEASE BEARING INSECT RESEARCH IN MALAYA BY JAPANESE SCIENTISTS DURING WORLD WAR II AND ITS POSITION IN INTERNATIONAL LAW

Japanese scientists commissioned by the Imperial Japanese Navy (IJN) were tasked at the Nettai Igaku Kenkyusho or Institute of Medical Research (IMR) in Kuala Lumpur and other locations in Malaya during World War II (WWII) to identify cures for malaria, dengue, and scrub typhus rampant among Japanese troops in Southeast Asia. Such research on insects could contribute to biological warfare. This study identifies the background and destiny of these few Japanese scientists in Malaya conducting research on malaria, dengue and scrub typhus while evaluating if their research could have been an offense under international law at that point of time. A qualitative historical approach relying on documentation, soft law, treaties, and secondary resources obtained from archives and national libraries online from different countries and the Fold3-Historical Military Records website were referred. These documentations were classified according to names of Japanese scientists to form a short biography and to provide background information of the IMR during WWII. The results reveal some Japanese scientists responsible for malaria research at the IMR in Kuala Lumpur and Penang, and dengue research in Malaya, Singapore and Java. Human experimentation associated with dengue was suspected in Singapore. One IMR Japanese director had links with Unit 731. Kiyoshi Hayakawa, part of Unit 9420 in Singapore, Japan’s subunit for its covert biological weapons programme conducted research on scrub typhus in Java and Malaya. These scientists continued as professors in Japan or were promoted to this position much later with one of them opening a medical company. Indeed, a gap existed in international law at the end of the 19th and early 20th century which failed to make experimentation illegal as a preparation stage rather than actual usage in warfare because of the omission to address the development, production and stockpiling of biological weapons.

Neurorights in History: A Contemporary Review of José M. R. Delgado’s “Physical Control of the Mind” (1969) and Elliot S. Valenstein’s “Brain Control” (1973)

Scholars from various disciplines discuss the ethical, legal, and social implications of neurotechnology. Some have proposed four concrete “neurorights”. This review presents the research of two pioneers in brain stimulation from the 1950s to 1970s, José M. R. Delgado and Elliot S. Valenstein, who also reflected upon the ethical, legal, and social aspects of their and other scientists’ related research. Delgado even formulated the vision “toward a psychocivilized society” where brain stimulation is used to control, in particular, citizens’ aggressive and violent behavior. Valenstein, by contrast, believed that the brain is not organized in such a way to allow the control or even removal of only negative processes without at the same time diminishing desirable ones. The paper also describes how animal and human experimentation on brain stimulation was carried out in that time period. It concludes with a contemporary perspective on the relevance of neurotechnology for neuroethics, neurolaw, and neurorights, including two recent examples for brain-computer interfaces.

The Missing Committees: Research Ethics in the Making in Switzerland

This article analyzes the formation of research ethics and particularly of ethics committees in Switzerland by tracing their early history along distinct phases: (1) the first guidelines on human experimentation issued by the Swiss Academy of Medical Sciences in 1970; (2) conceptual struggles in establishing these norms; (3) the emergence of a central medical-ethical committee in 1979; and (4) the first local ethics committee established in the rural canton of Thurgau in 1987. It analyzes the interplay between local practices, industrial standards, and a neoliberal, low-key, soft regulation by negotiation among peers. Key actors are the Swiss Academy of Medical Sciences, the pharmaceutical industry, and the canton of Thurgau. In this context, ‘research’ and ‘experiments’ for a long time remained disputed, unclear and risky notions. rec s were encouraged mainly as a way of distributing responsibility, of managing a wide array of risks and, crucially, as part of a wider strategy to avoid juridical and political regulation. The article asks, on a more general level, how and why ‘ethics’ entered this field and what becomes visible or obscured when issues are transposed into an ethical language.

“Localising Tropical Medicine”: A History of the Medical Research Institute (MRI) in Colonial Lagos, 1907–1920s

This article explores an early episode in the history of tropical medicine in colonial Lagos, British West Africa. It probes into the activities and outputs of scientists who operated within the Medical Research Institute (MRI) as a way to further complicate the agendas of tropical medicine. Scientists of the MRI undertook biomedical experimentation with a profound understanding of metropolitan and local imperatives as both determined the extent to which they contributed to popular discourses. The present paper explores the extent to which metropole-colony relations triggered local scientists at the MRI to resort to all available means, including human experimentation, in the course of ambitious scientific projects. In certain other contexts, international and local motivations converged to sway the ambivalent postures of colonial scientists to biomedical experimentation.

An Open-Source Modular Framework for Automated Pipetting and Imaging Applications

The number of samples in biological experiments are continuously increasing, but complex protocols and human experimentation in many cases lead to suboptimal data quality and hence difficulties in reproducing scientific findings. Laboratory automation can alleviate many of these problems by precisely reproducing machine-readable protocols. These instruments generally require high up-front investments and due to lack of open APIs they are notoriously difficult for scientists to customize and control outside of the vendor-supplied software. Here, we demonstrate automated, high-throughput experiments for interdisciplinary research in life science that can be replicated on a modest budget, using open tools to ensure reproducibility by combining the tools Openflexure, Opentrons, ImJoy and UC2. Our automated sample preparation and imaging pipeline can easily be replicated and established in many laboratories as well as in educational contexts through easy-to-understand algorithms and easy-to-build microscopes. Additionally, the creation of feedback loops, with later pipetting or imaging steps depending on analysis of previously acquired images, enables the realization of smart microscopy experiments, featuring completely autonomously performed experiments. All documents and source-files are publicly available (https://beniroquai.github.io/Hi2) to prove the concept of smart lab automation using inexpensive, open tools. We believe this democratizes access to the power and repeatability of automated experiments.