Smallpox Prevention and Public Healthcare in China in the 1920s and 1930s: Focusing on the Cases of Shanghai and Beijing.

Beijing and Shanghai, representative modern cities in China, witnessed the development of various urban infrastructures and quarantine systems in the 1920s and 1930s. Both cities established Health Demonstration Stations in the 1930s, as part of their implementation of modern health administration. This foundation played a pivotal role for making health administration more practical. Huang Zi-fang (1899-1940) and Hu Hung-ji (1894-1932), the inaugural directors of the health bureau in the respective cities, were both graduates of the Johns Hopkins University School of Public Health in the United States. They shared a similar view of public health. Active exchanges occurred between the heads of the health administration in the two cities who were the leading forces in the health reform, encompassing various health experiments including the Health Demonstration Station. During the 1930s in China, state medicine gained prominence as the most ideal medical model for constructing a modern state. As such, the quarantine activities they promoted were also considered the most ideal model. The public health care centered on Health Demonstration Stations in the 1920s and 1930s that developed in large Chinese cities such as Beijing and Shanghai pursued similar goals by strengthening quarantine administration through free medical treatment and modern spatial control. Nonetheless, each city exhibited differences in terms of the subjects and targets of quarantine, as well as the primary bases of quarantine, which were either Health Demonstration Stations or hospitals. Both municipal governments and the civilian sector led the sanitary infrastructure development. While Shanghai showed stronger development in terms of the number of vaccinations, Shanghai's dualized quarantine system did not necessarily create a better health environment than Beijing in terms of spatial control. In the 1940s, the Japanese occupation government implemented measures to inherit and further develop existing health administrations in Beijing and Shanghai. Existing international settlements were incorporated into the Japanese occupation government, and the occupation government pursued homogenization of urban space and tried to maintain the existing urban policy as much as possible to preserve the status quo. However, the intensification of the Anti-Japanese War and the Chinese Civil War brought an end to the health experiment centered around the Health Demonstration Station in China in the first half of the twentieth century.

The Disease Ecology, Epidemiology, Clinical Manifestations, Management, Prevention, and Control of Increasing Human Infections with Animal Orthopoxviruses.

Zoonotic orthopoxvirus outbreaks have occurred repeatedly worldwide, including monkeypox in Africa and the United States, cowpox in Europe, camelpox in the Middle East and India, buffalopox in India, vaccinia in South America, and novel emerging orthopoxvirus infections in the United States, Europe, Asia, and South America. Waning smallpox immunity may increase the potential for animal-to-human transmission followed by further community transmission person-to-person (as demonstrated by monkeypox and buffalopox outbreaks) and by contact with fomites (as demonstrated by camelpox, cowpox, and, possibly, Alaskapox). The objectives of this review are to describe the disease ecology, epidemiology, clinical manifestations, prevention, and control of human infections with animal orthopoxviruses and to discuss the association with diminished population herd immunity formerly induced by vaccinia vaccination against smallpox. Internet search engines were queried with key words, and case reports, case series, seroprevalence studies, and epidemiologic investigations were found for review.

Historical Perspective: What Constitutes Discovery (of a New Virus)?

A historic review of the discovery of new viruses leads to reminders of traditions that have evolved over 118 years. One such tradition gives credit for the discovery of a virus to the investigator(s) who not only carried out the seminal experiments but also correctly interpreted the findings (within the technological context of the day). Early on, ultrafiltration played a unique role in "proving" that an infectious agent was a virus, as did a failure to find any microscopically visible agent, failure to show replication of the agent in the absence of viable cells, thermolability of the agent, and demonstration of a specific immune response to the agent so as to rule out duplicates and close variants. More difficult was "proving" that the new virus was the etiologic agent of the disease ("proof of causation")-for good reasons this matter has been revisited several times over the years as technologies and perspectives have changed. One tradition is that the discoverers get to name their discovery, their new virus (unless some grievous convention has been broken)-the stability of these virus names has been a way to honor the discoverer(s) over the long term. Several vignettes have been chosen to illustrate several difficulties in holding to the traditions (vignettes chosen include vaccinia and variola viruses, yellow fever virus, and influenza viruses. Crimean-Congo hemorrhagic fever virus, Murray Valley encephalitis virus, human immunodeficiency virus 1, Sin Nombre virus, and Ebola virus). Each suggests lessons for the future. One way to assure that discoveries are forever linked with discoverers would be a permanent archive in one of the universal virus databases that have been constructed for other purposes. However, no current database seems ideal-perhaps members of the global community of virologists will have an ideal solution.

Assembly-line manipulation of droplets in microfluidic platform for fluorescence encoding and simultaneous multiplexed DNA detection.

In this article, a new mode of droplets manipulation is presented and applied for simultaneous multiplexed DNA detection. We call this droplets manipulation, "assembly-line manipulation of droplets (ALMD)". Firstly, multiple droplets containing the same target mixtures are generated in the microchannel, and then fused with later generated different droplets containing corresponding probes, respectively. Finally, all the fused droplets were fluorescence imaged on-line and real-time. The successful implementation of droplets fluorescence encoding based on ALMD shows the reproducibility and accuracy of this manipulation mode. As a proof-of-concept application, the simultaneous multiplexed DNA detection was carried out through the model of human immunodeficiency virus (HIV) gene sequence and variola virus (small pox, VV) gene sequence based on ALMD in the microfluidic system. It is proved that this method achieves simultaneous multiplexed DNA measurements with a significantly time-saving way and without different dye-labelled probes or complex operation procedures. In addition, it reveals the possibility of high-throughput biosensing with simple chip design and detection equipment.

Should remaining stockpiles of smallpox virus (variola) be destroyed?

In 2011, the World Health Organization will recommend the fate of existing smallpox stockpiles, but circumstances have changed since the complete destruction of these cultures was first proposed. Recent studies suggest that variola and its experimental surrogate, vaccinia, have a remarkable ability to modify the human immune response through complex mechanisms that scientists are only just beginning to unravel. Further study that might require intact virus is essential. Moreover, modern science now has the capability to recreate smallpox or a smallpox-like organism in the laboratory in addition to the risk of nature re-creating it as it did once before. These factors strongly suggest that relegating smallpox to the autoclave of extinction would be ill advised.

Smallpox virus destruction and the implications of a new vaccine.

The World Health Assembly is scheduled to decide in May 2011 whether the 2 known remaining stockpiles of smallpox virus are to be destroyed or retained. In preparation for this, a WHO-appointed committee undertook a comprehensive review of the status of smallpox virus research from 1999 to 2010. It concluded that, considering the nature of the studies already completed with respect to vaccine, drugs, and diagnostics, there was no reason to retain live smallpox virus except to satisfy restrictive regulatory requirements. The committee advised that researchers and regulators define alternative models for testing the vaccines and drugs. Apart from other considerations, the costs of new products are significant and important. These include prospective expenditures required for the development, manufacture, testing, and storage of new products. This commentary provides approximations of these costs and the incremental contribution that a newly developed vaccine might make in terms of public health security.

On genies and bottles: scientists' moral responsibility and dangerous technology R&D.

The age-old maxim of scientists whose work has resulted in deadly or dangerous technologies is: scientists are not to blame, but rather technologists and politicians must be morally culpable for the uses of science. As new technologies threaten not just populations but species and biospheres, scientists should reassess their moral culpability when researching fields whose impact may be catastrophic. Looking at real-world examples such as smallpox research and the Australian "mousepox trick", and considering fictional or future technologies like Kurt Vonnegut's "ice-nine" from Cat's Cradle, and the "grey goo" scenario in nanotechnology, this paper suggests how ethical principles developed in biomedicine can be adjusted for science in general. An "extended moral horizon" may require looking not just to the effects of research on individual human subjects, but also to effects on humanity as a whole. Moreover, a crude utilitarian calculus can help scientists make moral decisions about which technologies to pursue and disseminate when catastrophes may result. Finally, institutions should be devised to teach these moral principles to scientists, and require moral education for future funding.

Sensitive and selective viral DNA detection assay via microbead-based rolling circle amplification.

We report a sensitive and efficient magnetic bead-based assay for viral DNA identification using isothermal amplification of a reporting probe.