Pearls and Irritations

Technology to create a synthetic virus like the China new coronavirus is well established. It is widely available to some governments, private firms, and individuals.

And the pace of research has been advancing exponentially. Is it just a matter of time before an act of bioterrorism occurs?

Much research on synthetic biology is shrouded in secrecy, but the creation of new, potentially-harmful life forms has been progressing for decades, accelerating in the last three years. The latest techniques involve “gene editing”, which can create organisms-to-order even as controls on their creation and use are weak.

Development of bioweaponry was meant to be regulated by the 1972 Biological Weapons Convention (BWC), to which the vast majority of obviously bioweapons-capable nations are signatories; a notable exception being Israel. But the BWC has loopholes and lacks teeth. It allows “peaceful”/”defensive” development of bioweapons technology. And there is no verification and compliance provision. (1)

An international attempt was made in 2001 to strengthen the BWC by adding verification and compliance provisions, but this was rejected by the US, whose negotiating team incidentally was led by John Bolton, well-known supporter of US unilateralism.

As far back as 2001, the Lancet warned that the New York Times had alleged that the US government had been doing biological weapons research that “tests the limits” of the BWC. The newspaper report said that under the terms of the 2001 draft protocol that the US rejected, signatories would have had to allow inspectors to monitor the ban. The need to keep such projects secret was a significant reason behind President Bush’s rejection of the draft agreement, the Lancet reported. (2)

Many countries probably engage in bioweapons development. The US has been engaged in bioweaponry research since well before the turn of the century, under a programme to create “defensive” bioweapons.

But as Milton Leitenberg wrote in 2003, it is impossible to distinguish between offensive and defensive research (3). “Defensive” weapons can be deployed offensively. The only difference is “the intent” of the programme, he wrote.

How much risk does this research pose to civilian populations, who would be the target of bioterrorists?

Scientists are generally agreed that gene editing would be beyond ordinary unskilled people. But there is a constant risk from individuals who have been trained in government or commercial programmes.

In 2002, Eileen Choffnes warned of trained “insiders” going rogue. She noted that the 2001 anthrax letter attack in the US was done by an insider with laboratory training. (4)

The risk picture is complicated by the many commercial firms engaged in synthetic biology and gene editing for profit, restricted in their activities only by “self-regulation”.

Way back in 2010, Markus Fischer and Stephen Maurer complained that commercial gene synthesis companies routinely sell long strands of made-to-order DNA to researchers around the world. Observers had long speculated that individuals, terrorist organisations and governments could potentially use this DNA to create pathogens and other biosecurity threats. (5)

In 2012, Bracha Rager-Zisman warned that synthetic biology had raised increasing concerns about the danger of “dual use,” in which results for improving human well-being and the environment may be misappropriated for bioterror.

Rager-Zisman noted that biowarfare goes back to the beginning of recorded history. Its forms range from poisoned arrows, to poisoned well water, to the modern phenomena of salmonella-poisoned salad bars in restaurants, the dissemination of plague by aircraft, and the diffusion of deadly bacteria by targeted bombing. (6)

Among governments involved in biowarfare development, the US is determined not to be left behind, according to Sara Reardon, who in 2015 provided a glimpse into DARPA, the US Defense Advanced Research Projects Agency under the Department of Defense (DoD). DARPA is the leading agency involved in pushing cutting-edge research in any scientific field that could have military applications. It does so at a “frenetic” pace involving outside researchers, she wrote.

“At DARPA, much of the authority is vested in the programme managers, who rotate in and out from academia, industry and the armed services. They alone design the initiatives, invite researchers to apply for contracts with specific goals and milestones and select the groups they think are most likely to achieve the goals. Then they work closely with the researchers to guide the project as it proceeds. DARPA calls its grant recipients ‘performers’ – and if they do not meet their milestones, the axe can fall quickly,” Reardon wrote. (7)

In 2016, Filippa Lentzos wrote that the most significant misuse risks from synthetic biology do not arise from bioterrorists, but from “professional and well-resourced institutions like national militaries”.

She noted that in 2014, figures on US synthetic biology research funding showed that two thirds of the US$200 million invested in this field came from DoD or DARPA. DoD declared just over US$655 million on national biodefence research in 2014. “Synthetic biology research would appear, then, to make up about a fifth of the biodefence budget,” she wrote. (8)

In 2017, Marko Ahteensuu wrote that bioterrorists could use synthetic organisms “to target civilians, specific populations or even an individual person.”

“What brought biosecurity into the spotlight in 2006 was The Guardian journalist who managed to make an online order of fragments of the smallpox genome which were then delivered to his residential address. Indeed, there currently are a number of commercial companies that use DNA synthesisers and fulfil orders for constructed genetic material ranging from oligonucleotides to full genomes…,” Ahteensuu wrote, adding that it is relatively easy to establish a basic home lab in one’s garage or kitchen since guidance for setting it up can be found on the internet and the standard lab equipment is available for purchase. (9)

Also in 2017, Anthony King in the Irish Times noted: “Some readers may be surprised to learn that scientists engineer deadly viruses such as anthrax, flu and smallpox to make them more lethal. And engineered viruses could cause a disease outbreak. There is concern that parties with sinister intentions will hijack the technology and essentially propagate it as a weapon of bioterrorism”. (10)

In 2018, Bobmanuel Echeonwu, et al. wrote that “the ease and low cost with which biological agents may be dispersed is also a cause for concern.” Conventional weapons use cost US$2000/sq km to inflict civilian casualties; the equivalent costs for nuclear weapons and biological weapons would be US$800/sq km and US$1/sq km respectively. Bioterrorists can engineer biological agents that target specific races, creating a stealth virus capable of incorporating itself into the DNA of such targeted populations, they wrote. (11)

Kathleen Vogel and Sonia Ouagrham-Gormley in 2018 pointed to a new revolutionary gene-editing technology: “CRISPR (clustered regularly interspaced short palindromic repeats) is heralded as an important new innovation because it seemingly produces mutations much faster, with greater precision, and at a lower cost than previous gene-editing techniques. Additionally, scientists have recently used CRISPR to create and “drive” edited genes through organisms. These so-called gene drives ensure that, through natural reproduction, edited genes are passed on to the offspring of genetically altered organisms, thus ensuring that the edited genes are spread from one generation to the next.” (12)

How prepared are healthcare systems for disasters in general and bioterrorism in particular? Among many issues identified, there is the need to strengthen the public health infrastructure (13), to provide adequate funding to deal with patient “surge” (14), and training for early detection and diagnosis of cases (15).

In 2019, Manfred Green, et al., in Lancet Infectious Diseases, provided a 12-point checklist to consider. The list includes factors like preparedness for intentional outbreaks, high level leadership, the need for health-care providers and emergency rooms to be aware of the manifestations of biological agents with bioterrorism potential, personal protective equipment to become more user-friendly, improved surge capacity, capacity of laboratories, new and improved vaccines (pre-exposure and post-exposure) and treatment regimens, clinical and environmental surveillance, stockpile of vaccines and medications, and international cooperation. (16)

Notes:

(1) Block, S. M. (2001). The growing threat of biological weapons. American Scientist, 89(1), 28-37.

(2) US biological defence research under the spotlight. (2001). The Lancet, 358(9285), 895.

(3) Leitenberg, M. (2003). Distinguishing offensive from defensive biological weapons research. Critical Reviews in Microbiology, 29(3), 223-57.

(4) Choffnes, E. (2002). Bioweapons: New labs, more terror? Bulletin of the Atomic Scientists, 58(5), 28-32.

(5) Fischer, M., & Maurer, S. M. (2010). Harmonizing biosecurity oversight for gene synthesis. Nature Biotechnology, 28(1), 20-2.

(6) Rager-Zisman, B. (2012). Ethical and regulatory challenges posed by synthetic biology. Perspectives in Biology and Medicine, 55(4), 590-607.

(7) Reardon, S. (2015). The Military-Bioscience Complex. Nature, 522(7555), 142-144.

(8) Lentzos, F. (2016). Biology’s misuse potential. Connections : The Quarterly Journal, 15(2), 48-64.

(9) Ahteensuu, M. (2017). Synthetic biology, genome editing, and the risk of bioterrorism. Science and Engineering Ethics, 23(6), 1541-1561.

(10) King, A. (2017, Sep 07). At the very limits of scientific endeavour: Intentionally mutating viruses to make them more deadly; genetically modifying germs . . . is science going too far? Irish Times

(11) Echeonwu, B., Nwankiti, O., Chollom, S., & Olawuyi, K. (2018). Bioterrorism threat: A review of microbial forensics source-tracing of some bioterrorism agents. Journal of Forensic Science and Medicine, 4(3), 161-166.

(12) Vogel, K. M., & Sonia Ben Ouagrham-Gormley. (2018). Anticipating emerging biotechnology threats: A case study of CRISPR. Politics and the Life Sciences, 37(2), 203-219.

(13) Idzikowski, L. (Ed.). (2019). Chemical and biological warfare. Greenhaven Publishing LLC, pp. 149-156.

(14) Healthcare systems still have work to do to be better prepared for next disaster. (2018). Briefings on Hospital Safety, 26(6), 4.

(15) Razak, S., Hignett, S., & Barnes, J. (2018). Emergency department response to chemical, biological, radiological, nuclear, and explosive events: A systematic review. Prehospital and Disaster Medicine, 33(5), 543-549.

(16) Green, M. S., LeDuc, J., Cohen, D., & Franz, D. R. (2019). Confronting the threat of bioterrorism: Realities, challenges, and defensive strategies. The Lancet Infectious Diseases, 19(1), e2-e13.

(John Tan was a deputy editor in the Straits Times newspaper in Singapore. He has been foreign editor and business editor.)

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