BillG ‘Bioterrorism more likely than a pandemic,’ Gates warns "A bioterrorist attack that could wipe out 30 million people in less than a year is becoming increasingly likely because it is easier than ever to create and spread deadly pathogens, Microsoft founder Bill Gates warned during an interview with the United Kingdom’s Telegraph newspaper. In fact, an act of bioterrorism is more likely than a pandemic, he warned, and a lethal respiratory pathogen such as a recreated smallpox virus could be more dangerous than a nuclear attack. Gates, whose charitable foundation funds research into quickly spotting outbreaks, said it was more important than ever to help foreign countries monitor diseases to prevent a global tragedy." cbc1 How recreating horsepox in a lab could lead to cancer cures You just call up a company and say I need some DNA? I mean first of all they want to know who you are and what you're doing with it. And of course it's not trivial to design the clones when we had to tell them exactly what sequences we want and we also had to order some very special bits as it were because the virus had some unusual genome features that needed to be copied. Is this something anyone could do? There are these people called bio-hackers, mostly in the U.S., who do contact these companies and they can order certain DNA sequences. But all the reputable companies will take the sequence that you're ordering and run it through computers to figure out what it is you're doing. So for example horsepox is considered a Level 2 agent and that would be usable. But if you were to try and order any of the really dangerous viruses, Ebola or things like that, they would ask questions and might well call CSIS. cbc2 Why there's finally a drug for smallpox even though the disease no longer exists Fortunately, it doesn't exist anymore. After a global vaccination campaign, smallpox was declared eradicated in 1980. So why has the U.S. Food and Drug Administration announced its approval of tecoviramat (brand name TPOXX) — the first medication for this terrible disease? The answer is defence against bioterrorism. In fact, the drug manufacturer's first customer is the U.S. government's Biomedical Advanced Research and Development Authority. df1 It’s Getting Too Easy to Create Dangerous Viruses It took David Evans’ team of scientists at the University of Alberta in Edmonton, Canada, about six months and $100,000 to recreate the horsepox virus, a close relative of the smallpox virus that killed perhaps 300 million people in the 20th century before it was eradicated in 1980. In a summary of the research, the World Health Advisory Committee on Variola Virus Research wrote that “recreation of such viral genomes did not require exceptional biochemical knowledge or skills, significant funds, or significant time.” EJ DIY horsepox created from mail-order DNA prompts search for new gene editing rules at U of A An extinct horsepox virus — cousin of the deadly smallpox virus — has now been stitched together by University of Alberta researchers and now law professors at the school are drafting a policy to regulate gene editing research. In January, David Evans and Ryan Noyce published a paper in the free journal PLOS One that detailed their steps to build horsepox from scratch. The paper explained how their team bought and assembled bits of mail-order DNA from the internet, and shared how the resulting virus was able to infect cells and reproduce. The entire project took about six months and cost about US$100,000. Internationalmedia, including the New York Times and severalscience journals, reported on the research. It drew fire from critics who worried the scientific blueprint was a how-to guide for recreating deadly viruses that could cause harm on a large scale. They also worried the research was happening in a wild west-style policy vacuum. Gammon 2010 VACCINIA VIRUS DNA POLYMERASE AND RIBONUCLEOTIDE REDUCTASE: THEIR ROLE IN REPLICATION, RECOMBINATION AND DRUG RESISTANCE Examining Committee Dr. David Evans, Department of Medical Microbiology and Immunology, University of Alberta gryphon ROADMAP FOR IMPEMENTING BIOSECURITY AND BIODEFENSE POLICY IN THE UNITED STATES The key findings and conclusions from this case study are: • The existing regulatory system for governing life sciences research in the United States is overlapping and if implemented well, could result in review and oversight of research involving synthesis of an extinct pathogen and an orthopoxvirus. • If followed exactly as written, biosecurity policies would not apply to synthesis of horsepox virus. However, biosafety and ethics policies likely would trigger review and oversight of such research even though security experts did not raise these concerns. Hughes 2009 The Evolutionary Biology of Poxviruses The poxviruses (family Poxviridae) are a family of double-stranded viruses including several species that infect humans and their domestic animals, most notably Variola virus (VARV), the causative agent of smallpox. The evolutionary biology of these viruses poses numerous questions, for which we have only partial answers at present. Here we review evidence regarding the origin of poxviruses, the frequency of host transfer in poxvirus history, horizontal transfer of host genes to poxviruses, and the population processes accounting for patterns of nucleotide sequence polymorphism. Conclusion This brief review has shown that the study of poxviruses raises a number of intriguing evolutionary questions, which are far from being revolved. These questions include the following: the origin of poxviruses and dsDNA viruses in general; the origin of specific poxviruses such as VARV; the role of horizontal gene transfer in poxvirus evolution; and the population processes that explain patterns of nucleotide sequence polymorphism. Modern evolutionary genetics, thanks to an increased understanding of the stochastic nature of the evolutionary process (Kimura 1983; Nei 1987), provides a powerful conceptual arsenal for understanding population processes. These concepts are particularly useful when applied with an appreciation for the realities of each species natural history, including (in the case of viruses infecting humans) time of origin as human pathogens, existence of non-human reservoirs, modes of transmission, and so forth. Unfortunately, progress in evolutionary biology has been stalled by the widespread use of invalid statistical methods and by a mentality inherited from the early days of Neo-Darwinism that sees natural selection as an all-powerful force fine-tuning every aspect of the phenotype (Hughes 2007b). This review is written in the hope that virologists will take a lead in combating such outworn attitudes and in advancing a genuine understanding of the process that shape viral evolution. Lederman Wikipedia "This article contains content that is written like an advertisement. Please help improve it by removing promotional content and inappropriate external links, and by adding encyclopedic content written from a neutral point of view." (July 2018) Lederman 2018 Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments Edward Jenner and his contemporaries believed that his variolae vaccinae originated in horses and molecular analyses show that modern vaccinia virus (VACV) strains share common ancestry with horsepox virus (HPXV). Given concerns relating to the toxicity of modern VACV vaccines, we asked whether an HPXV-based vaccine might provide a superior alternative. Since HPXV may be extinct and the only specimen of HPXV that has been identified is unavailable for investigation, we explored whether HPXV could be obtained by large-scale gene synthesis. Ten large (10–30 kb) fragments of DNA were synthesized based on the HPXV sequence along with two 157 nt VACV terminal sequences, and were recombined into a live synthetic chimeric HPXV (scHPXV) in cells infected with Shope fibroma virus (SFV). Sequencing of the 212 kbp scHPXV confirmed it encoded a faithful copy of the input DNA. We believe this is the first complete synthesis of a poxvirus using synthetic biology approaches. This scHPXV produced smaller plaques, produced less extracellular virus and exhibited less virulence in mice than VACV, but still provided vaccine protection against a lethal VACV challenge. Collectively, these findings support further development of scHPXV as a novel replication-proficient smallpox vaccine.

MedLine Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments US National Library of Medicine National Institutes of Health mims The puzzling origin of the smallpox vaccine "However, in synthesizing the horsepox virus, the group led by virologist David Evans of the University of Alberta in Edmonton, Canada has also recreated the eradicated smallpox virus – a scandalous reason for which Evans’ research has been denied and unpublished. The World Health Organization has forbidden for the full smallpox genome to be reconstructed or to breed live smallpox virus in the lab." natpost Canadian synthesizes a better smallpox vaccine — just in case terrorists bring the disease back Made from synthesized horsepox, it's believed to be a virtual clone of the original 1796 smallpox vaccine which developed hazardous side effects over time. npr Did Pox Virus Research Put Potential Profits Ahead of Public Safety? "using the natural virus might have prevented the pharmaceutical company he is working with from commercializing horsepox as a new vaccine" pr1 Tonix Pharmaceuticals Announces Demonstrated Vaccine Activity in First-Ever Synthesized Chimeric Horsepox Virus NEW YORK, March 02, 2017 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq:TNXP) (Tonix), a company that is developing innovative pharmaceutical products to address public health challenges, working with researchers from the University of Alberta, a leading Canadian research university, today announced the successful synthesis of a potential smallpox-preventing vaccine. This vaccine candidate, TNX-801, is a live form of horsepox virus (HPXV) that has been demonstrated to have protective vaccine activity in mice. pr2 Successful Development of TNX-801 May Lead to an Improved Smallpox-Preventing Vaccine NEW YORK, Jan. 19, 2018 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq:TNXP) (Tonix), a company developing innovative pharmaceutical and biological products to address major public health challenges, today announced the publication of research describing the successful synthesis and characterization of a potential smallpox-preventing vaccine based on horsepox virus. The research was conducted in conjunction with scientists from the University of Alberta, a leading Canadian research university. Sciencemag How Canadian researchers reconstituted an extinct poxvirus for $100,000 using mail-order DNA "A group led by virologist David Evans of the University of Alberta in Edmonton, Canada, says it has synthesized the horsepox virus, a relative of smallpox, from genetic pieces ordered in the mail. Horsepox is not known to harm humans—and like smallpox, researchers believe it no longer exists in nature; nor is it seen as a major agricultural threat. But the technique Evans used could be used to recreate smallpox, a horrific disease that was declared eradicated in 1980. "No question. If it’s possible with horsepox, it’s possible with smallpox,” says virologist Gerd Sutter of Ludwig Maximilians University in Munich, Germany." sec Tonix Pharmaceuticals Announces Publication Reporting Synthesis, Construction and Characterization of a Potential Smallpox-Preventing Vaccine Candidate TNX-801 (Live Horsepox Virus from Cell Culture) NEW YORK, Jan. 19, 2018 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix), a company developing innovative pharmaceutical and biological products to address major public health challenges, today announced the publication of research describing the successful synthesis and characterization of a potential smallpox-preventing vaccine based on horsepox virus. The research was conducted in conjunction with scientists from the University of Alberta, a leading Canadian research university. wiki Poxviridae Poxviridae is a family of viruses. Humans, vertebrates, and arthropods serve as natural hosts. There are currently 69 species in this family, divided among 28 genera, which are divided into two subfamilies. Diseases associated with this family include smallpox.[1][2] Four genera of poxviruses may infect humans: orthopoxvirus, parapoxvirus, yatapoxvirus, molluscipoxvirus. Orthopox: smallpox virus (variola), vaccinia virus, cowpox virus, monkeypox virus; Parapox: orf virus, pseudocowpox, bovine papular stomatitis virus; Yatapox: tanapox virus, yaba monkey tumor virus; Molluscipox: molluscum contagiosum virus (MCV).[3] The most common are vaccinia (seen on Indian subcontinent) and molluscum contagiosum, but monkeypox infections are rising (seen in west and central African rainforest countries). The similarly named disease chickenpox is not a true poxvirus and is actually caused by the herpesvirus varicella zoster. History "Diseases caused by pox viruses, especially smallpox, have been known about for centuries. One of the earliest suspected cases is that of Egyptian pharaoh Ramses V who is thought to have died from smallpox circa 1150 years BCE.[22][23] Smallpox was thought to have been transferred to Europe around the early 8th century and then to the Americas in the early 16th century. It is widely accepted that the main defeat of the Aztecs was due to a smallpox epidemic and within two years over 3.2 million Aztecs died. This death toll can be attributed to the American population's complete lack of exposure to the virus over millennia. A century after Edward Jenner showed that the less potent cow pox could be used to effectively vaccinate against the more deadly smallpox, a worldwide effort to vaccinate everyone against smallpox began with the ultimate goal to rid the world of the plague-like epidemic. The last case of endemic smallpox occurred in Somalia in 1977. Extensive searches over two years detected no further cases, and in 1979 the World Health Organization (WHO) declared the disease officially eradicated. In 1986, all virus samples were destroyed or transferred to two approved WHO reference labs: at the headquarters of the federal Centers for Disease Control and Prevention (the C.D.C.) in Atlanta, Georgia (the United States) and at the Institute of Virus Preparations in Moscow.[24] Post September 11, 2001 the American and UK governments have had increased concern over the use of smallpox, or a smallpox like disease, in bio-terrorism." Atlantic A Controversial Virus Study Reveals a Critical Flaw in How Science Is Done After researchers resurrected a long-dead pox, some critics argue that it's too easy for scientists to make decisions of global consequence. This controversy is the latest chapter in an ongoing debate around “dual-use research of concern”—research that could clearly be applied for both good and ill. More than that, it reflects a vulnerability at the heart of modern science, where small groups of researchers and reviewers can make virtually unilateral decisions about experiments that have potentially global consequences, and that everyone else only learns about after the fact. Cue an endlessly looping gif of Jurassic Park’s Ian Malcolm saying, “Your scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should.” Take the horsepox study. Evans was a member of a World Health Organization committee that oversees smallpox research, but he only told his colleagues about the experiment after it was completed. He sought approval from biosafety officers at his university, and had discussions with Canadian federal agencies, but it’s unclear if they had enough ethical expertise to fully appreciate the significance of the experiment. “It’s hard not to feel like he opted for agencies that would follow the letter of the law without necessarily understanding what they were approving,” says Kelly Hills, a bioethicist at Rogue Bioethics. She also sees a sense of impulsive recklessness in the interviews that Evans gave earlier this year. Science reported that he did the experiment “in part to end the debate about whether recreating a poxvirus was feasible.” And he told NPR that “someone had to bite the bullet and do this.” To Hills, that sounds like I did it because I could do it. “We don’t accept those arguments from anyone above age 6,” she says. The same debates played out in 2002, when other researchers synthesized poliovirus in a lab. And in 2005, when another group resurrected the flu virus behind the catastrophic 1918 pandemic. And in 2012, when two teams mutated H5N1 flu to be more transmissible in mammals, in a bid to understand how that might happen in the wild. Many of the people I spoke with expressed frustration over this ethical Möbius strip. “It’s hard not to think that we’re moving in circles,” Hills says. “Can we stop saying we need to have a conversation and actually get to the conversation?”