John Collins Warren and his act of conscience: a brief narrative of the trial and triumph of a great surgeon.
On examination of the correspondence among the principals involved, as well as the original patent application being prepared by Morton, it has become possible to reconstruct some of the remarkable details attending the first use of ether anesthesia at the Massachusetts General Hos pital in the autumn of 1846. At the time that Warren invited Morton to demonstrate the use of his "ethereal vapor" for anesthesia in a minor operation on Oct. 16, 1846, the exact chemical composition of the agent used was being held secret by Morton; Warren was clearly disturbed by this unethical use of a secret "nostrum." When the time arrived 3 weeks later for its possible use for a serious "capital" operation, Warren employed a simple stratagem of public confrontation to discover from Morton the true nature of the substance to be used. On being informed that it was pure unadulterated sulfuric ether, not some mysterious new discovery labeled "Letheon," Warren gave approval for its first use in a "capital" operation (low thigh amputation) on Nov. 7, 1846. Despite this revelation to the immediate participants, a veil of secrecy continued to surround the substance for many months, an anomalous situation evidently traceable to Morton's desire for personal reward from the discovery. It was this matter of secrecy, rather than priority for its discovery, that surrounded the early use of ether anesthesia with controversy and recrimination both in this country and abroad. (+info
The pneumococcus at the millennium: not down, not out.
In the 12 decades that will have elapsed between the first isolation of the pneumococcus and the coming millennium, much of fundamental biologic importance has been learned from the study of this bacterium and the diseases it causes. Streptococcus pneumoniae is associated with the development of Gram's stain, the Quellung reaction, and many of the fundamentals of immunology. It has also played a significant role in the history of antimicrobial therapy. After a transitory period of euphoria engendered by the improved prognosis of pneumococcal pneumonia resulting from therapeutic advances, recognition that the newer treatments could not bring about the recovery of those sustaining early irreversible physiologic injury led to renewed interest in immunoprophylaxis. Added impetus to this approach has been fostered by the recent rapid increase in the number of pneumococcal isolates resistant to antimicrobial agents and in the magnitude of their resistance. Pneumococcal vaccines are increasingly relevant. (+info
Early theory and research on hemispheric specialization.
This article provides an account of early theory and research on hemispheric specialization. It begins by tracing theory and research on localization of function that set the stage for the discovery of hemispheric specialization. After that, it describes the studies of Paul Broca, John Hughlings-Jackson, and others on hemisphere specialization and reviews some of the proposed explanations for the phenomenon. It then turns to the study of hemispheric specialization and mental illness, and it ends by identifying some of the linkages between theory and research from the past and the present. (+info
An appreciation of A.E. Malloch, MB, MD (1844-1919): a forgotten surgical pioneer.
Dr. Archibald Edward Malloch was a surgeon whose life and work were greatly influenced by Joseph Lister and his revolutionary system of antiseptic surgery. This paper describes how a young Canadian medical man came to introduce Lister's system to North America in 1869 and studies his career in the light of Lister's surgical epoch. (+info
Vitamin A as "anti-infective" therapy, 1920-1940.
In the last fifteen years, a large series of controlled clinical trials showed that vitamin A supplementation reduces morbidity and mortality of children in developing countries. It is less well known that vitamin A underwent two decades of intense clinical investigation prior to World War II. In the 1920s, a theory emerged that vitamin A could be used in "anti-infective" therapy. This idea, largely championed by Edward Mellanby, led to a series of at least 30 trials to determine whether vitamin A--usually supplied in the form of cod-liver oil--could reduce the morbidity and mortality of respiratory disease, measles, puerperal sepsis, and other infections. The early studies generally lacked such innovations known to the modern controlled clinical trial such as randomization, masking, sample size and power calculations, and placebo controls. Results of the early trials were mixed, but the pharmaceutical industry emphasized the positive results in their advertising to the public. With the advent of the sulfa antibiotics for treatment of infections, scientific interest in vitamin A as "anti-infective" therapy waned. Recent controlled clinical trials of vitamin A from the last 15 y follow a tradition of investigation that began largely in the 1920s. (+info
Rapid economic growth and 'the four Ds' of disruption, deprivation, disease and death: public health lessons from nineteenth-century Britain for twenty-first-century China?
Rapid economic growth has always entailed serious disruption: environmental, ideological, and political. As a result the relationship between economic growth and public health is complex since such disruption always threatens to spill over into deprivation, disease and death. The populations of most current high-income, high-life expectancy countries of 'the West' endured several decades of severely compromised health when they first experienced industrialization in the last century Although health technologies have moved on, the social, administrative and political disruption accompanying economic growth can still impede the delivery of health improvements. The case history of 19th-century laissez-faire Britain is explored in some detail to demonstrate the importance of these social and political forces, particularly the relative vigour and participatory nature of local government, linking to recent work on the importance of social capital in development. For a country like China today, paradoxically, there is nothing that needs such careful planning as a 'free market' economy. (+info
Chemical hormesis: its historical foundations as a biological hypothesis.
Despite the long history of hormesis-related experimental research, no systematic effort to describe its early history has been undertaken. The present paper attempts to reconstruct and assess the early history of such research and to evaluate how advances in related scientific fields affected the course of hormesis-related research. The purpose of this paper is not only to satisfy this gap in current knowledge but also to provide a foundation for the assessment of how the concept of hormetic dose-response relationships may have affected the nature of the bioassay, especially with respect to hazard assessment practices within a modern risk assessment framework. (+info
Milestones in the research on tobacco mosaic virus.
Beijerinck's (1898) recognition that the cause of tobacco mosaic disease was a novel kind of pathogen became the breakthrough which eventually led to the establishment of virology as a science. Research on this agent, tobacco mosaic virus (TMV), has continued to be at the forefront of virology for the past century. After an initial phase, in which numerous biological properties of TMV were discovered, its particles were the first shown to consist of RNA and protein, and X-ray diffraction analysis of their structure was the first of a helical nucleoprotein. In the molecular biological phase of research, TMV RNA was the first plant virus genome to be sequenced completely, its genes were found to be expressed by cotranslational particle disassembly and the use of subgenomic mRNA, and the mechanism of assembly of progeny particles from their separate parts was discovered. Molecular genetical and cell biological techniques were then used to clarify the roles and modes of action of the TMV non-structural proteins: the 126 kDa and 183 kDa replicase components and the 30 kDa cell-to-cell movement protein. Three different TMV genes were found to act as avirulence genes, eliciting hypersensitive responses controlled by specific, but different, plant genes. One of these (the N gene) was the first plant gene controlling virus resistance to be isolated and sequenced. In the biotechnological sphere, TMV has found several applications: as the first source of transgene sequences conferring virus resistance, in vaccines consisting of TMV particles genetically engineered to carry foreign epitopes, and in systems for expressing foreign genes. TMV owes much of its popularity as a research mode to the great stability and high yield of its particles. Although modern methods have much decreased the need for such properties, and TMV may have a less dominant role in the future, it continues to occupy a prominent position in both fundamental and applied research. (+info