Author: Billwilliam Reviewer: Irene
This is a summary of chapter 4 (part 1) of the PLA’s biowarfare textbook “The Unnatural Origin of SARS-1 and the Man-made Human Virus as a Genetic Bioweapon“. Chapter 4 is quite long, so I will explain it in two articles: this is part 1. I skipped chapter 3, which is purely about biological concepts such as evolution, mutation, and phylogenetic trees.
Chapter 4: Contemporary Genetic Bioweapon (Emerging Human Infectious Pathogens and Infectious Genes) and Its Release Methods
The defining features of contemporary genetic bioweapons
According to section 1 of chapter 4, a contemporary bioweapon should have the following features distinguished from traditional bioweapons. The author used the word “contemporary bioweapon”, but they meant next-generation bioweapon. Basically, these are bioweapons with CCP characteristics — the focus is on how to make a bioweapon appear “natural” in origin. A genetically edited bioweapon is further optimized by serial passage and adaptive trials in animal models so that the pathogen is more adapted to infect humans. Mutations will erase the marks of artificial gene editing. (pages 84-85)
- Traditional bioweapons are enhanced versions of existing pathogens. Contemporary bioweapons are created by genetic editing followed by serial passage and adaptive trials in animal models—this process can modify animal pathogen into a novel, artificial pathogen for humans.
- Traditional bioweapons are usually released as aerosols. Contemporary bioweapons, in contrast, are first applied to infect animals in the target area, and the animals will in turn infect humans.
- Contemporary bioweapons are sometimes released as pathogen-carrying animals.
- Contemporary bioweapons may be used for purposes beyond war. The authors wrote on page 85: “In contrast to traditional genetic bioweapons, the contemporary genetic bioweapon is not for military purposes, but for the critical needs of terrorist blackmail, politics, and regional or international strategy in the absence of a world war. Although war or military action is an important last-resort option for political missions, it’s too obvious and will draw condemnation from the world. If contemporary bioweapons are used, the process is clandestine, and evidence collection is difficult. Even if evidence from academia or hard evidence like viruses or animals are provided, the attacker can deny, thwart, or suppress the truth. This will render international organizations and righteous persons helpless.” The original Chinese text is shown below.
- The outcome from such a bioweapon attack is severe and unpredictable. The released pathogen may persist for decades in the target area.
Contemporary bioweapons are very stealthy
The authors cited the 2001 anthrax letter attack in the US to illustrate how difficult it is to investigate a bioweapon terrorist attack. Nine years after the attack, the FBI still couldn’t conclusively identify the culprit who launched the bioweapon attack. A traditional bioweapon attack like anthrax is already awfully hard to investigate, and new contemporary bioweapons are even stealthier and harder to detect. (section 2, pages 85-88)
The six types of contemporary bioweapons
The authors cited Michael Ainscough’s (Colonel, USAF) article “Next generation bioweapons” to describe six types of novel bioweapons. (section 3, pages 89-98)
* *Binary bioweapon* *
A binary bioweapon is made of two innocuous components that form a dangerous pathogen when mixed. For instance, a bacteria’s virulence can be greatly enhanced in the presence of virulent plasmids. The two components of a binary bioweapon are usually kept separately and only mixed right before deployment.
The authors also referred to the example of creating yellow fever-influenza A chimeric virus particle by fusion of viral envelopes.
* *Designer genes* *
Based on current knowledge of biochemistry and genomes of different species, a completely new organism can be designed and even artificially synthesized. An artificial influenza virus strain can be created to mimic the natural mutation of the influenza virus. An artificial pathogen can be assembled from different modules or parts. Modern technology may soon be able to synthesize mycoplasma, a genus of bacteria with the smallest genome. It is also possible to synthesize viruses.
* *Gene therapy as a bioweapon* *
Gene therapy is a process to integrate an artificial sequence permanently into the target genome. A vector-like retrovirus is often employed to insert a sequence into the human genome to replace a faulty gene. This process can be weaponized if done in reverse, such as replacing good genes with bad genes.
* *Stealth viruses* *
Stealth viruses remain dormant after infecting the genome of a population. They can be activated by an external stimulus to cause viral diseases. For example, herpes viruses usually stay dormant but will cause lesions if activated by external stimulus. Stealth virus bioweapon can be used for blackmail.
Stealth DNA is oncogenes or oncogene-like viruses that can be activated to cause cancer.
* *Host-swapping diseases* *
This is converting an animal virus into a human virus, meaning the virus has jumped the species barrier to infect humans. An animal virus may be genetically edited or deliberately modified to infect humans.
Under natural conditions, it takes an animal virus decades or hundreds of years to cross the species barrier. However, serial passage or adaptive trials can greatly expedite the process. A bioweapon made by such a process may appear to be the product of natural mutation, but the evolutionary time is too short. A virus is probably a bioweapon if it evolves at a rate that is several times of natural evolution.
The authors mentioned two gain-of-function experiments published in 2012. Both experiments illustrate that serial passage or adaptive trials in animal models could induce enough mutations to make the H5N1 avian flu virus airborne. In the first set of experiments, Sander Herfst and his group first modified H5N1 avian flu by site-directed mutagenesis and serial passage in ferrets. Airborne transmission experiments were later done to select for the virus strain that spread the most easily by the airborne route.
In the second experiment, Masaki Imai and his group first screened for an optimum H5N1/H1N1 recombinant strain for binding with receptors in the human respiratory system. They then conducted serial passage in ferrets to select the most infectious virus strain. Both experiments demonstrate that serial passage or adaptive trials can be conducted to make a virus airborne and to optimize it for infecting humans.
* *Designer Diseases* *
Because of advancements in cell and molecular biology, it might be possible to design an artificial pathogen for hypothetical symptoms. Designer diseases may have mechanisms such as shutting down the immune system, inducing cancer, or switching on programmed cell death.
Genetic bioweapons like designer diseases, designer genes, and stealth viruses are similar in concept. All six types of contemporary bioweapons involve some level of designing a novel pathogen or agent for infecting humans.
By the definitions above, COVID-19 is probably a host-swapping bioweapon. According to Dr. Li-meng Yan, the template of this bioweapon is the Zhoushan bat virus. The PLA genetically edited the spike of the template virus (such as swapping in a receptor binding motif that can bind with human ACE2) to make it capable of infecting humans. They then carried out their signature move — serial passage in animal models — to make COVID-19 appear to be from natural mutations. However, Dr. Yan could still pinpoint several marks of artificial gene editing.
“Next Generation Bioweapons“, Colonel Michael Ainscough.
“Airborne transmission of influenza A/H5N1 virus between ferrets“, Herfst, S., et al., Science 2012, 336 (6088): 1534-1541.
“Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets“, Imai, M., et al., Nature, 2012, 486 (7403): 420-428.