Lampreys and spinal cord regeneration: "a very special claim on the interest of zoologists," 1830s-present.

Employing history of science methods, including analyses of the scientific literature, archival documents, and interviews with scientists, this paper presents a history of lampreys in neurobiology from the 1830s to the present. We emphasize the lamprey's roles in helping to elucidate spinal cord regeneration mechanisms. Two attributes have long perpetuated studies of lampreys in neurobiology. First, they possess large neurons, including multiple classes of stereotypically located, 'identified' giant neurons in the brain, which project their large axons into the spinal cord. These giant neurons and their axonal fibers have facilitated electrophysiological recordings and imaging across biological scales, ranging from molecular to circuit-level analyses of nervous system structures and functions and including their roles in behavioral output. Second, lampreys have long been considered amongst the most basal extant vertebrates on the planet, so they have facilitated comparative studies pointing to conserved and derived characteristics of vertebrate nervous systems. These features attracted neurologists and zoologists to studies of lampreys between the 1830s and 1930s. But, the same two attributes also facilitated the rise of the lamprey in neural regeneration research after 1959, when biologists first wrote about the spontaneous, robust regeneration of some identified CNS axons in larvae after spinal cord injuries, coupled with recovery of normal swimming. Not only did large neurons promote fresh insights in the field, enabling studies incorporating multiple scales with existing and new technologies. But investigators also were able to attach a broad scope of relevance to their studies, interpreting them as suggesting conserved features of successful, and sometimes even unsuccessful, CNS regeneration. Lamprey research demonstrated that functional recovery takes place without the reformation of the original neuronal connections, for instance, by way of imperfect axonal regrowth and compensatory plasticity. Moreover, research performed in the lamprey model revealed that factors intrinsic to neurons are integral in promoting or hindering regeneration. As this work has helped illuminate why basal vertebrates accomplish CNS regeneration so well, whereas mammals do it so poorly, this history presents a case study in how biological and medical value have been, and could continue to be, gleaned from a non-traditional model organism for which molecular tools have been developed only relatively recently.

"You've Got to Work on This Axon": J. Z. Young and Squid Giant Axon Preparations in 20th -Century Neurobiology.

Employing and extending Hans-Jörg Rheinberger's analytical concept of epistemic things, this essay proposes one reason why squid giant axons, unusually large invertebrate nerve fibers, had such great impacts on twentieth-century neurobiology. The 1930s characterizations of these axons by John Zachary Young reshaped prevailing assumptions about nerve cells as epistemic things, I argue. Specifically, Young's preparations of these axons, which consisted of fibers attached to laboratory technologies, highlighted similarities between giant axons and more familiar ones via lines of comparative study common to aquatic biology. Young's work convinced other biologists that the squid giant fibers were, in fact, axons, despite their unusual fused (syncytial) structures, thereby promoting further studies, such as intracellular measurements, made possible by the fiber's size. Tracing direct relations between preparations of squid axons and broader interpretations of neurons as epistemic things, this paper renders an actors' category, "preparations," into an analytical one. In turn, it offers glimpses into how aquatic organisms shaped twentieth-century neurobiology and how local experiments can drive broader, disciplinary changes.

The Bermuda Triangle: The Pragmatics, Policies, and Principles for Data Sharing in the History of the Human Genome Project.

The Bermuda Principles for DNA sequence data sharing are an enduring legacy of the Human Genome Project (HGP). They were adopted by the HGP at a strategy meeting in Bermuda in February of 1996 and implemented in formal policies by early 1998, mandating daily release of HGP-funded DNA sequences into the public domain. The idea of daily sharing, we argue, emanated directly from strategies for large, goal-directed molecular biology projects first tested within the "community" of C. elegans researchers, and were introduced and defended for the HGP by the nematode biologists John Sulston and Robert Waterston. In the C. elegans community, and subsequently in the HGP, daily sharing served the pragmatic goals of quality control and project coordination. Yet in the HGP human genome, we also argue, the Bermuda Principles addressed concerns about gene patents impeding scientific advancement, and were aspirational and flexible in implementation and justification. They endured as an archetype for how rapid data sharing could be realized and rationalized, and permitted adaptation to the needs of various scientific communities. Yet in addition to the support of Sulston and Waterston, their adoption also depended on the clout of administrators at the US National Institutes of Health (NIH) and the UK nonprofit charity the Wellcome Trust, which together funded 90% of the HGP human sequencing effort. The other nations wishing to remain in the HGP consortium had to accommodate to the Bermuda Principles, requiring exceptions from incompatible existing or pending data access policies for publicly funded research in Germany, Japan, and France. We begin this story in 1963, with the biologist Sydney Brenner's proposal for a nematode research program at the Laboratory of Molecular Biology (LMB) at the University of Cambridge. We continue through 2003, with the completion of the HGP human reference genome, and conclude with observations about policy and the historiography of molecular biology.

Sharing Data to Build a Medical Information Commons: From Bermuda to the Global Alliance.

The Human Genome Project modeled its open science ethos on nematode biology, most famously through daily release of DNA sequence data based on the 1996 Bermuda Principles. That open science philosophy persists, but daily, unfettered release of data has had to adapt to constraints occasioned by the use of data from individual people, broader use of data not only by scientists but also by clinicians and individuals, the global reach of genomic applications and diverse national privacy and research ethics laws, and the rising prominence of a diverse commercial genomics sector. The Global Alliance for Genomics and Health was established to enable the data sharing that is essential for making meaning of genomic variation. Data-sharing policies and practices will continue to evolve as researchers, health professionals, and individuals strive to construct a global medical and scientific information commons.