Biological Warfare: Smallpox and Monkeypox
Smallpox and, to a lesser extent, monkeypox are critical viral agents of interest to terrorist groups and rogue states. Smallpox, being a highly contagious infectious disease, has a high mortality rate, whereas monkeypox is poorly transmitted from person to person and has a reduced mortality rate, but is easily extracted from nature or animal reservoirs and then genetically modified, for example, to increase virulence. [1] [2] [3]
A trained bioterrorist only needs to spray the virus in a crowded place for the irreparable to happen. A silent and inconspicuous release will allow an invisible aerosol cloud of odorless and tasteless virus particles to spread instantly. At the same time, no one will know that he or she has been infected, until days or even weeks have passed before the first symptoms and signs of illness. Until they appear, the infected person will infect healthy people. The viral infection will gain the strength of an epidemic.
Smallpox viruses officially remain in only two laboratories, Atlanta (Georgia, USA) and Koltsovo (Novosibirsk Oblast, Russia). Nevertheless, the threat of bioterrorism is more than real. Attackers could recreate the virus based on its publicly available genome sequence and then use it as a biological weapon. [4] Illegal repositories of smallpox virus cannot be ruled out. [5] [6] [7] The virus could be preserved in smallpox dead human remains found during archaeological excavations in permafrost. [8] [9] [10]
With the vast majority of people currently unvaccinated against smallpox, nearly the entire world population remains defenseless against both smallpox, which has decimated entire cities for thousands of years, and other infections caused by orthopoxviruses.
In 2016, a team of Canadian researchers led by virologist David Evans carried out a terrifying experiment. Scientists synthesized Horsepox virus (HSPV) from mail-order genetic fragments. This virus, thought to no longer exist in nature, is completely harmless to humans, but the very fact of de novo viral synthesis directly demonstrates the clear threat of bioterrorism. It would take a small team of specialists, not particularly blessed with any exceptional biochemical knowledge or skills, six months and approximately $100,000 to bring back to life smallpox, now securely buried. [11]
Evans’ group purchased overlapping DNA fragments, each about 30,000 base pairs (bp) long, from a company engaged in commercial DNA synthesis from a given amino acid sequence. The fragments were stitched together into a 212,000 bp Horsepox virus genome. Introduction of the genome into cells infected with another type of poxvirus triggered the cellular production of infectious Horsepox virus particles. Finally, the virus was grown, sequenced, and characterized.
The production of smallpox virus by this method is forbidden by the World Health Organization (WHO) and many countries’ regulations: Laboratories are not allowed to synthesize more than 20% of the viral genome. However, controlling every nucleic acid company in the world is a decidedly hopeless task.
The Evans experiment is a dual-purpose study. In addition to publicly gin up the threat of bioterrorism, there is an important academic challenge. It turns out that the vaccine that Edward Jenner used to inoculate people against smallpox en masse, beginning in the 18th century, is not known to have originated. It is the most successful vaccine in human history, the basis of modern immunology and microbiology, and is a live virus called Vaccinia virus, but its origin has been a big mystery until now. It was believed that the roots of the Jenner vaccine came from the Horsepox virus.
As a result, this was established, and Tonix Pharmaceuticals set out to develop TNX-801, a new smallpox vaccine based on Horsepox virus synthesized by Evans’ group, believing it would prove less toxic. In addition, the proposed reverse genetic synthesis method could be adapted to assemble other poxviruses with great promise in immuno-oncology as oncolytic agents using constructs based on personalized tumor neoantigens. [12]
What Is Smallpox
Smallpox was completely defeated in 1980. It took an incredible effort by the World Health Organization (WHO), which launched a worldwide mass vaccination campaign against smallpox in 1959 and intensified it in 1967. A special role was played by the USSR, which eradicated smallpox from its territory as early as 1936. The USSR, first, proposed the idea of mandatory worldwide smallpox vaccination and, second, provided 1.5 billion doses of vaccines and medical personnel for WHO purposes. The U.S. and Sweden also made significant contributions to the campaign. The eradication of smallpox cost the world $298 million, which translates to approximately $1.9 billion in 2022 prices. It’s a tiny amount compared to all the terrible consequences of this infectious disease. [1] [2]
Smallpox is caused by Variola major and Variola minor, two strains of Variola virus belonging to the genus Orthopoxvirus of the family Poxviridae. The disease has been known to mankind since ancient times. The lethality of smallpox transmitted by airborne droplets or by contact with infected objects and items is so high (at least 30%) that for thousands of years it was a veritable curse. Thus, in the XVIII century annually 400,000 Europeans gave grim tribute to this “the greatest of all the ministers of death,” and a third of all cases of blindness accounted for smallpox. It was not until 1796 that the British physician and scientist Edward Jenner was the first to publish evidence of the effectiveness of the inoculation using the cowpox virus to prevent smallpox and gave recommendations for the manufacture of the vaccine. By the way, centuries earlier, variolation was successfully practiced by the Chinese, who blew smallpox scabs into the nostrils of healthy people. Nevertheless, even in the 20th century smallpox claimed 300–500 million lives and mutilated or disfigured many more people in the process.
The last natural case of smallpox was documented in the fall of 1977. Since the only natural host of the virus was humans and the virus could not survive more than two days in the environment, on May 8, 1980, WHO announced the complete eradication of smallpox from the planet. Scheduled vaccination against smallpox was discontinued worldwide by 1985.
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