{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:17:28Z","timestamp":1784193448410,"version":"3.55.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"7-8","license":[{"start":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T00:00:00Z","timestamp":1588723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","award":["1137582"],"award-info":[{"award-number":["1137582"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Smallpox, caused by variola virus, was eradicated in 1980, but remains a category A bioterrorism agent. A decade ago, smallpox ranked second after anthrax in a multifactorial risk priority scoring analysis of category A bioterrorism agents. However, advances in genetic engineering and synthetic biology, including published methods for synthesizing an Orthopoxvirus, require the assumptions of this scoring for smallpox and other category A agents to be reviewed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>The risk priority framework was reviewed and revised to account for the capability for creation of synthetic or engineered smallpox and other category A agents.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The absolute score for all agents increased because of gene editing and synthetic biology capability, which was not present when the framework was developed more than a decade ago, although new treatments revised scores downward for smallpox, Ebola, and botulism. In the original framework, smallpox scored 0 for global availability, given the high security around known seed stocks of variola in two laboratories in the United States and Russia. Now, smallpox can be created using synthetic biology, raising the score for this criterion to 2. Other agents too, such as Ebola, score higher for availability, based on synthetic biology capability. When advances in synthetic biology and genetic engineering are considered, smallpox and anthrax are now equally ranked the highest category A bioterrorism agents for planning and preparedness.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Revision of a risk priority framework for category A bioterrorism agents shows that smallpox should be elevated in priority for preparedness planning, and that gene editing and synthetic biology raises the overall risk for all agents. The ranking of categories A, B, and C agents should also be revisited, as there is an endless possibility of engineered threats that may be more severe than any agent on the category A list.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/milmed\/usaa084","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T13:06:50Z","timestamp":1588770410000},"page":"e952-e957","source":"Crossref","is-referenced-by-count":22,"title":["Reevaluating the Risk of Smallpox Reemergence"],"prefix":"10.1093","volume":"185","author":[{"given":"C Raina","family":"MacIntyre","sequence":"first","affiliation":[{"name":"Biosecurity Program, The Kirby Institute, UNSW Medicine, University of New South Wales, Sydney 2052, Australia"},{"name":"College of Health Solutions and College of Public Service and Community Solutions, Arizona State University, Phoenix, AZ 85287"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"issue":"6","key":"2020081706164626700_ref1","doi-asserted-by":"crossref","first-page":"e0217704","DOI":"10.1371\/journal.pone.0217704","article-title":"Health system capacity in Sydney, Australia in the event of a biological attack with smallpox","volume":"14","author":"MacIntyre","year":"2019","journal-title":"PLoS One"},{"issue":"4","key":"2020081706164626700_ref2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.3201\/eid2404.171233","article-title":"Influence of population immunosuppression and past vaccination on smallpox reemergence","volume":"24","author":"MacIntyre","year":"2018","journal-title":"Emerg Infect Dis"},{"issue":"11","key":"2020081706164626700_ref3","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1093\/molbev\/msy153","article-title":"Bayesian phylogeography and pathogenic characterization of smallpox based on HA, ATI, and crMB genes","volume":"35","author":"Adam","year":"2018","journal-title":"Mol Biol Evol"},{"issue":"1","key":"2020081706164626700_ref4","first-page":"74","article-title":"Epidemic size, duration and vaccine stockpiling following a large-scale attack with smallpox","volume":"1","author":"MacIntyre","year":"2019","journal-title":"Global Biosecurity"},{"key":"2020081706164626700_ref5","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1136\/bmj.1.4348.628","article-title":"Aerial convection from smallpox hospitals","volume":"1944","author":"Millard","year":"1944","journal-title":"Br Med J"},{"key":"2020081706164626700_ref6","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1136\/bmj.1.4350.699-b","article-title":"Aerial convection from smallpox hospitals","volume":"1944","author":"Easton","year":"1944","journal-title":"Br Med J"},{"issue":"2","key":"2020081706164626700_ref7","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/713610418","article-title":"An epidemiological analysis of the 1971 smallpox outbreak in Aralsk, Kazakhstan","volume":"29","author":"Zelicoff","year":"2003","journal-title":"Crit Rev Microbiol"},{"issue":"1","key":"2020081706164626700_ref8","doi-asserted-by":"crossref","first-page":"e0188453","DOI":"10.1371\/journal.pone.0188453","article-title":"Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments","volume":"13","author":"Noyce","year":"2018","journal-title":"PLoS One"},{"issue":"1","key":"2020081706164626700_ref9","first-page":"28","article-title":"Efficacy of three key antiviral drugs used to treat orthopoxvirus infections: a systematic review","volume":"1","author":"Yu","year":"2019","journal-title":"Global Biosecurity"},{"issue":"3","key":"2020081706164626700_ref10","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1128\/JVI.75.3.1205-1210.2001","article-title":"Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox","volume":"75","author":"Jackson","year":"2001","journal-title":"J Virol"},{"key":"2020081706164626700_ref11","volume-title":"Bioterrorism Agents\/Diseases","author":"Center for Disease Control and Prevention (CDC)"},{"issue":"7","key":"2020081706164626700_ref12","doi-asserted-by":"crossref","first-page":"589","DOI":"10.7205\/MILMED.171.7.589","article-title":"Development of a risk-priority score for category A bioterrorism agents as an aid for public health policy","volume":"171","author":"MacIntyre","year":"2006","journal-title":"Mil Med"},{"issue":"10","key":"2020081706164626700_ref13","doi-asserted-by":"crossref","first-page":"e1007025","DOI":"10.1371\/journal.ppat.1007025","article-title":"Synthetic horsepox viruses and the continuing debate about dual use research","volume":"14","author":"Noyce","year":"2018","journal-title":"PLoS Pathog"},{"issue":"6213","key":"2020081706164626700_ref14","doi-asserted-by":"crossref","first-page":"1258096","DOI":"10.1126\/science.1258096","article-title":"Genome editing. 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