A new bioweapon system?
A contribution to the proceedings of Working Group 1
89th Executive Council Meeting of the WFSW
Paris, 29-30 April 2019
The use of biological agents as a means to weaken or destroy an enemy party in a conflict is probably as old as mankind itself. In the course of History there are several notable instances of this use.
In the crudest ways such as using the bodies of dead soldiers or animals to contaminate water wells or catapulting cadavers within the walls of a besieged city , a demonstration that Military leaders in the Middle Ages recognized that victims of infectious diseases could become weapons themselves. In more “sophisticated” ways, like, in North America, the distribution of blankets infected with smallpox to decimate the population of Indian tribes hostile to the British (1763).
In the period mediating between the end of the Great War and the beginning of WW II, several “developed” nations conducted research programmes on the development of bioweapons; the Japanese programme, deserves a special reference for the breadth of the means involved in the programme that included the setup of a research centre, known as the Unit 731, with a staff that exceeded 3000 scientists, mainly microbiologists. Experiments were conducted on prisoners of war, mainly Koreans, Chinese and Russian soldiers that were used to test a number of bioweapons. It has been reported that during this research, several thousand prisoners died as a result of the experiments conducted on them.
In 1942, the British army tested anthrax dirty bombs on the Island of Gruinard, off the Scotland coast. The island was contaminated and uninhabitable until 1990, when extensive land decontamination was carried out.
In the second half of the 20th century and especially in the last quarter of the century, both the USSR and the USA invested in ambitious research programmes with the purpose of developing and producing bioweapons.
Bioweapons have in some respects considerable “advantages” over other types of weapons, naturally from the point of view of the fighting parties. One is its very low cost compared with other conventional or non-conventional weapons: bioweapons are cheaper when the purpose is to eliminate human lives on a given area of application say, per square kilometer of a piece of land inhabited by civilians. In 1969 United States experts have disclosed the following estimates of the cost per square kilometer of an attack to civilian populations using different weapons: 1 US$ for bioweapons, 600 US$ for chemical, 800 US$ for nuclear and 2,000 US$ for conventional armaments. These figures have to be interpreted as concerning comparable loss of lives but not the destruction of material goods, buildings or infra-structures.
When considering bioweapons, anthrax, a disease caused by a spore-forming bacterial agent developed in the second half of the last century, deserves a special reference. Anthrax was developed as part of larger biological weapon programmes carried out in several countries including the United States and the Soviet Union. As pointed out by Md Radzi Johari  in the six years from 1989 to 1995, the number of nations believed to have biological weapon programmes have risen from 10 to 17.
Dr. Stefan Riedel remarks that “the number and identity of countries that have engaged in offensive biological weapons research is largely still classified information. However, it can be accurately stated that the number of state sponsored programmes of this type has increased significantly during the past 30 years”.
Anthrax can be easily produced by non-state actors as has happened with the Japanese Aum Shinrikyo religious sect, remembered for releasing sarin gas in an underground railway station in Tokio.
It is generally recognized by experts that biologic agents existing or under development can be misused in offensive programmes directed at civilian populations but also against staple crops or livestock on which their subsistence depends.
The Biological Weapons Convention
The Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction (usually referred to as the Biological Weapons Convention) was the first multilateral disarmament treaty banning the production of an entire category of weapons.
Fifty years earlier, biological weapons were internationally banned by the 1925 Geneva Convention. The Convention had a limited reach, and in fact state bio warfare programmes continued and even expanded during World War II and the Cold War. In 1972, the major powers agreed on a draft of a new Convention submitted by the UK. The new text was adopted and submitted for signature on the 10th April of that year. It became effective on March 26, 1975 after ratification by 22 states. As of September 2018, 182 states had become party to the Convention. Among the small number of developed non-signatories states, Israel is the most conspicuous.
Article 1 of the BWC reads as follows:
“Each State Party to this convention undertakes never in any circumstances to develop, produce, stockpile or otherwise acquire or retain:
- Microbiological or other biological agents, or toxins whatever their origin or method of production, of types or in quantities that have no justification for prophylactic, protective or other peaceful purposes”
Thus, the Convention prohibits any misuse of biotechnology in offensive biological programmes directed against human beings and their staple crops or livestock. It sets however no limitations on their use in “defensive biological programmes” which gives a wide margin for interpretation. In other words: the treaty bans the creation of biological arsenals and outlaws offensive biological research, though defensive research is permissible.
The ascent of gene editing techniques and its implications
It has recently become public that DARPA, the Defense Advanced Research Project Agency, an agency of the United States Department of Defense ,has launched a few years ago a research programme called “Insect Allies”. This on-going programme, funded by DARPA, is “pursuing scalable, readily deployable, and generalizable countermeasures against potential natural and engineered threats to the food supply with the goals of preserving the U.S. crop system”.
Engaged in this programme are several academic institutions working under contract with DARPA.
A key aspect of the programme is that at its heart lies an emerging technology known as “gene editing” and the seemingly very effective editing tool known as CRISPR-Cas9. CRISPR-Cas9 is a unique technology that enables geneticists and medical researchers to edit parts of the genome by removing, adding or altering sections of the DNA sequence present in a gene. It targets what we can call a sentence in the genetic book of life and rewrites it. It is a novel tool considered to be faster, cheaper and more accurate than previous techniques of editing DNA .
It is common knowledge among minimally scientifically literate people that every living organism contains molecules of DNA, which carries genetic information. Genes are the pieces of DNA that carry this information, and they influence the properties of an organism. Genes determine an individual’s general appearance and to some extent their behavior. If two organisms are closely related, their DNA will be very similar.
Altering genetic information of a living organism have consequences that are not necessarily beneficial to the organism. It is probably safe to say that every old or new technology developed by humans can be looked upon as a two edged sword. As science advances at an increasingly fast pace it lays the foundations for the development of new emerging technologies more powerful and more effective in interfering with the natural world that includes humankind.
Gene editing is one of such emerging technologies.
The CRISPR-Cas9 system is an atomic structure organized in two key molecules: one is an enzyme (Cas9) that acts as a pair of molecular scissors that can cut the two strands of the DNA helix at a specific location in the genome so that bits of DNA can then be added or removed; the other is a molecule called guide RNA. Contrary to DNA which is a two stranded polymer molecule, RNA is a single stranded molecule. The guide RNA in the CRISPR system contains within the longer RNA molecular scaffold a predesigned RNA sequence of bases that matches the specific sequence in the targeted DNA sequence in the genome. The guide RNA will only bind to the targeted sequence and no other regions of the genome.
The Cas9 enzyme follows the guide RNA to the same location in the DNA sequence and makes a cut across both strands of the DNA.
At this stage the cell recognises that the DNA is damaged and tries to repair it.
In fact, cells have evolved a number of mechanisms to detect and repair the various types of damage that can occur to DNA. The DNA repair machinery can lead to adding or deleting pieces of genetic material, or making changes to the DNA by replacing an existing segment with a customized DNA sequence.
The crux of the matter is how the repair process is controlled.
Once the target gene is cut an edited version must be supplied for the cell to use as a template when it fixes the damage.
The “Insect Allies” research programme is explicitly directed towards gene editing of food crops using a CRISPR system engineered to be part of a virus. Such an approach would target specific plant genes by modifying chromosomes. It appears that maize would be one of the main intended targets.
It is known that plants are capable of receiving genetic information from viruses by the so-called “horizontal gene transfer”. Horizontal gene transfer involves DNA acquired from unrelated organisms whereas in vertical gene transfer, DNA is inherited from a parental organism. The research programme funded by the U.S. Defense Advanced Research Projects Agency aims to disperse infectious genetically modified viruses that have been engineered to edit crop chromosomes directly in fields.
The dispersion agent that is being considered are insects — the allies. Blake Bextine, the DARPA programme manager for Insect Allies, points out that “Insects eat plants and insects transmit the majority of plant viruses. (…) DARPA plans to harness the power of this natural system by engineering genes inside plant viruses that can be transmitted by insects to confer protective traits to the target plants they feed upon.”
In DARPA’s announcement of the new programme, posted on her website in October 2016, one can read the following:
“One of the most effective existing methods for protecting plants—selective breeding of disease resistance—typically involves five to seven years of work to identify the relevant protective genes and another 10 years or more to propagate the desired traits throughout plant populations. Insect Allies aims to effect the expression of desired traits within a single season. Performers will be challenged to develop compatible systems of naturally occurring plant viruses, herbivorous insects, and target crops, then genetically tune these systems to maximize transmission and uptake of traits across the entire target plant population with zero transmission to non-target plants.”
A quote of the programme manager in the same announcement reads as follows: “Genetic modification of plants has historically been done only to plant embryos inside of laboratories using tissue cultures. (…)Transforming mature plants en masse would be an enormous achievement and pave the way for future breakthroughs in agriculture.” 
Several authors have expressed the opinion that the technology involved in the programme is a blatant instance of a “dual use” technology. As such it is imperative that it be the object of careful consideration by the global scientific community and by citizens in general as natural stakeholders in its development and future application.
DARPA’s presentation of the programme’s objectives emphasizes the benefits thereof for routine agricultural use. Concerns with national security are clearly expressed in the DARPA’s official press-release: “National security can be quickly jeopardized by naturally occurring threats to the crop system, including pathogens, drought, flooding, and frost, but especially by threats introduced by state or non-state actors.” The reference to “threats introduced by state or-non-state actors” indicates that an aggression by foreign agents is contemplated. The new technology would then be used for defensive purposes.
Such statements should not be taken at face value, though. Especially when one has in mind the very nature of DARPA. Quoting Annie Jacobsen: “Everything there is dual purpose (…) you have to remember DARPA’s job isn’t to help people. It’s to create vast weapon systems of the future.” 
It is a fact that the vast majority of frontline emergency measures to control insect pests for both agriculture and health continue to rely on spraying, even for pest species where control measures based on the release of live insects have been developed (e.g., sterile males) .
In the case of an attack “by state or-non-state actors” an effective response would depend on the viability of rapidly scaling-up the mass production of insects which is something that certainly belongs to the realm of fiction.
On the contrary mass production of insect vectors may well be prepared in advance in case an offensive action is decided. Anyhow, experts point out that “it is very much easier to kill or sterilize a plant using gene editing than it is to make it herbicide or insect-resistant”.
Also there is no clear answer on how to guarantee the limits of the area affected by the dispersion of the virus carrying insects thus preventing contamination of neighboring fields. This question is relevant when dealing with routine agricultural uses but ceases to be relevant when the insect dispersion has offensive purposes.
Under the circumstances, as pointed out by R. G. Reeves, “the programme may be widely perceived as an effort to develop biological agents for hostile purposes and their means of delivery, which—if true—would constitute a breach of the Biological Weapons Convention (BWC)”.
2019, Feb. 19
 “Bioweapons and Bioterrorism: A Review of History and Biological Agents”, Orlando Cenciarelli, Silvia Rea, Mariachiara Carestia, Fabrizio D’Amico, Andrea Malizia, Carlo Bellecci, Pasquale Gaudio, Antonio Gucciardino, Roberto Fiorito, Defence S&T Tech. Bull., 6(2): 111-129, 2013
 See “ Biological Weapons Convention”, Wikipedia (https://en.wikipedia.org/wiki/Biological_Weapons_Convention)
 The Defense Advanced Research Projects Agency (DARPA) is an agency of the United States Department of Defense responsible for the development of emerging technologies for use by the military. Originally known as the Advanced Research Projects Agency (ARPA), the agency was created in February 1958 by President Dwight D. Eisenhower in response to the Soviet launching of Sputnik 1 in 1957. By collaborating with academic, industry, and government partners, DARPA formulates and executes research and development projects to expand the frontiers of technology and science, often beyond immediate U.S. military requirements (https://en.wikipedia.org/wiki/DARPA)
 “Agricultural research, or a new bioweapon system?”, R. G. Reeves , S. Voeneky , D. Caetano-Anollés , F. Beck , C. Boëte, Science 05 Oct 2018, Vol. 362, Issue 6410, pp. 35-37
 Maize or corn, wheat and rice are the main staple foods in many parts of the world.
 Leafhopper, whiteflies or aphids are examples believed to be contemplated
 See reference 12
 Annie Jacobsen is an American investigative journalist, author and 2016 Pulitzer Prize finalist in history. She authored the book “The Pentagon’s Brain: An Uncensored History of DARPA, America’s Top-Secret Military Research Agency”, Published September 22nd 2015 by Little, Brown and Company
 See reference 12