Wednesday, October 22, 2014

Smallpox, now online!



Fig.1. Transmission electron micrograph depicts smallpox virus virions (Mag. 370,000x). Credit: Dr. F. Murphy and S. Whitfield, CDC-PHIL #1849.

In 1979, the World Health Assembly declared the world free from smallpox. This virulent disease killed about 300 million people in the 20th century alone and reached all corners of the Earth. Decisive multilateral and bilateral efforts to eradicate the disease officially began in 1966 and ended with the last naturally occurring case in Somalia in 1977. A recent New York Times opinion piece, however, argued that the smallpox could return with a vengeance.

In “Resurrecting Smallpox? Easier Than you Think,” Dr. Leonard Adleman, a University of Southern California professor of computer science and molecular biology, said that online and open-access pathogen genomes represented a very real danger. Just as medical advances in the 20th century revolutionized public health - vaccines, antibiotics, higher living standards, sanitation, etc. - so have molecular advances in the 21st century changed how we think of medicine. April 2003 marked the end of the Human Genome Project, a decade-long feat to map all the genes in the human genome. Scientists can map genomes, from animals to microbes, in order to examine similarities, differences, mutations, and evolution within a species.

 

Digital collections of the 21st century

The increasingly inexpensive ability to map the entire genetic code of a pathogen yields some obvious benefits. Scientists can pinpoint when a microbe becomes pathogenic. They can examine how pathogens interact with vectors and participate in complex human biology on the genetic level. Unfortunately, as Adleman mentioned, this technology comes with dangerous consequences.

Although object-based scientific collections consist of physical specimens, an assortment of digitally-represented genomes may also be considered a collection. The age of digitizing makes collections easier to access, especially as more institutions are cataloguing their specimens online. But it also creates a gray area with distinguishing collections from pure data. Additionally, many online genomes are “open-access,” meaning that they are free for public use.

GenBank®, the National Institutes of Health genetic sequence database, is one such collection of publicly available DNA sequences. This powerful tool allows researchers to study pathogens on the genetic level, but it also creates a bioterrorism threat, to which Adleman referred.











Fig.2. Part of GenBank L22579.1 Variola major virus genome, causative agent of smallpox (strain Bangladesh-1975). Complete genome was found on GenBank using simple search tools. (Massung et al. 1993).

 

Bioterrorism danger and precaution

We no longer vaccinate against smallpox and are therefore vulnerable to a bioterrorist attack using the deadly virus. Although government committees found it more harmful than good to curb open-access online tools, they recognized the danger of “online pathogens.” Terrorists, with the right funding and scientific knowledge, could potentially create a weapon, or weapons, that kills millions through disease.

Luckily, we are not so defenseless, as many sensationalist articles claim. Government agencies constantly monitor Dual Use Research of Concern, or life sciences research that could be misapplied to pose a broad threat to public health, agriculture, the environment, or national security. The CDC has extensive preparation and planning programs for known bioterrorism agents and diseases.

Although the blueprints for diseases are accessible online, resources and methods with which to distribute the agent are more difficult to find. The lab infrastructure, detailed scientific knowledge, and ability to disperse a disease are all challenges bioterrorists must overcome. Biosafety precautions created by the United States government are meant to prevent such attacks. As we saw with the NIH and the CDC, however, lapses can occur.

As long as biosafety standards are secured, genomic knowledge of pathogens give insight into how these microbes function. Open-access digital gene banks contribute to the modern method of studying organisms, in which we analyze them from the molecular level to the macro-level. To limit such knowledge is to limit untold discoveries of how pathogens interact with their environment and human systems. Many scientific revelations may have dangerous consequences or applications, but that all depends on how we apply our research. In this era of digitization, our understanding of research and research tools has dramatically shifted for more accessibility than ever before.

References:

Adleman, L. (2014, Oct 14). Resurrecting Smallpox? Easier Than You Think. New York Times. Retrieved from http://www.nytimes.com/2014/10/16/opinion/resurrecting-smallpox-easier-than-you-think.html?_r=1.

All About the Human Genome Project (HGP). (2014, March 18). In National Human Genome Research Institute, NIH online. Retrieved from http://www.genome.gov/10001772#top.

Biosecurity: Dual Use Research of Concern. (n.d.). In NIH Office of Science Policy online. Retrieved from http://osp.od.nih.gov/office-biotechnology-activities/biosecurity/dual-use-research-concern.

Emergency Preparedness and Response. (2013, Nov 15). In CDC online. Retrieved from: http://www.bt.cdc.gov/bioterrorism/prep.asp.

GenBank Overview. (n.d.). In NCBI online. Retrieved from http://www.ncbi.nlm.nih.gov/genbank.

Massung,R.F., Esposito,J.J., Liu,L.-I., Qi,J., Utterback,T.R., Knight,J.C., Aubin,L., Yuran,T.E., Parsons,J.M., Loparev,V.N., Selivanov,N.A., Cavallaro,K.F., Kerlavage,A.R., Mahy,B.W.J. & Venter,J.C. (1993). Potential virulence determinants in terminal regions of variola smallpox virus genome. Nature 366 (6457) 748-751. Retrieved from http://www.ncbi.nlm.nih.gov/nuccore/L22579.1.

Murphy, F., & Whitfield, S. (Content Providers). Smallpox virus virions TEM PHIL 1849 [transmission electron micrograph]. Media comes from CDC Public Health Image Library, ID #1849. Retrieved from http://en.wikipedia.org/wiki/Smallpox#mediaviewer/File:Smallpox_virus_virions_TEM_PHIL_1849.JPG.

World Health Organization. (1980). The Global Eradication of Smallpox: Final Report of the Global Commission for the Certification of Smallpox Eradication, Geneva, December 1979 (History of International Public Health No. 4). Geneva, Switzerland. Retrieved from: http://whqlibdoc.who.int/publications/a41438.pdf.




Glossary

genome
The complete genetic material of an organism. A genome includes all the necessary information to build and maintain that organism. The genome is written in DNA/RNA code by chemical base pairs symbolized by letters (A, T, G, C, and U).
Dual Use Research of Concern (DURC)
Life sciences research that could provide knowledge, information, products etc. which could be misapplied to pose a significant threat with broad consequences to public health, agriculture, the environment, or national security.

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