A Growing Threat: Deliberate, Simultaneous Release of Pandemic Viruses Across Travel Hubs

·  Viruses can spread faster than vaccines or antivirals can be distributed.

·  Pandemic agents are more lethal than nuclear devices and will be accessible to terrorists.


·  A pandemic test-ban treaty will delay proliferation without slowing beneficial advances.

·  Liability and insurance for catastrophic outcomes will compensate for negative externalities.

·  Secure and universal DNA synthesis screening can reduce unauthorised access by >100-fold.


·  Untargeted sequencing can reliably detect all exponentially spreading biological threats

Goal: eliminate the virus while providing food, water, power, law enforcement, and healthcare

·  Develop and distribute pandemic-proof protective equipment for all essential workers

·  Comfortable, stylish, durable powered respirators must be proven to work reliably

·  Foster resilient supply chains, local production, and behavioural outbreak control

·  Strengthen systems and offer individualised early warning to block transmission

·  Develop and install germicidal low-wavelength lights, which appear to be harmless to humans

·  Overhead fixtures can reduce airborne and surface pathogens by >90 per cent in seconds

Relative to nuclear weapons, pandemic-class agents are comparably lethal and will be far more accessible

The international community has gone to immense lengths to prevent non-state actors from acquiring nuclear weapons. However, COVID-19 has demonstrated that even relatively mild pandemic viruses can kill more people than any nuclear device. While pandemic-class agents would be strategically useless to nation-states due to their slow spread and indiscriminate lethality, they might be acquired and deliberately released by terrorists.

Numerous independent advances in virology and biotechnology, none of which is obviously threatening on its own, have recently combined to render many viruses accessible to skilled individuals at a low cost. Stepby-step assembly protocols capable of producing infectious viruses from a genome sequence and standard laboratory reagents are widely available,(1) with particularly detailed and reliable instructions for influenzaviruses and coronaviruses, the families responsible for the last five respiratory pandemics.(2) Such protocols, which are intended to obviate the requirement for “tacit knowledge” to successfully perform the experiment, have become increasingly common. The recent democratisation of biotechnology suggests that they have broadly succeeded: the typical advance made in a cuttingedge laboratory by individuals with doctorates has required just one year to be reproduced in other laboratories, three years to be adapted for use in other contexts, five years to be reproduced by undergraduates and individuals with moderate skills, and 12-13 years to become accessible to high school students and others with low skills and resources.(3)

Today, perhaps 30,000 individuals with doctorates currently possess the skills(4) to follow the most straightforward virus assembly protocols: the United States has awarded approximately 2500 doctorates in virology in the past 20 years,(5) at least three times as many scientists in more common disciplines such as synthetic biology, bioengineering, and biomedicine also work with viruses and can follow such protocols, and the United States trains approximately one-third of such scientists worldwide.(6) No clinical samples are required: due to exponentially falling sequencing costs, most virus genome sequences are shared publicly soon after discovery, allowing them to be assembled from commercially available synthetic DNA, which is now widely available at a low and exponentially falling cost (see graph).(7) While members of the International Gene Synthesis Consortium, an industry group concerned about the prospect of misuse, screen customers and DNA synthesis orders for hazards at considerable expense, it is easy to find nonmembers that presumably do not.(8)

While sequenced viruses are widely accessible, pandemic proliferation and misuse cannot yet occur because we lack key knowledge: there are still no credible examples of viruses likely to cause new pandemics. As soon as someone identifies a single capable virus and shares its complete genome sequence, many thousands of people will immediately be able to generate infectious samples that could start a new pandemic. A list of many such viruses would allow a suitably skilled and resourced individual to ignite more pandemics simultaneously than would naturally occur in a century.

This future appears bleak and frightening. There is a natural temptation to reject it, and search for reasons to believe that the life sciences, which have given us cures for so many diseases, could not possibly pose a threat comparable to nuclear weapons. As a biologist and biotechnologist, I find the temptation to disbelieve nearly overwhelming. If human actions could never yield globally catastrophic consequences, then faster, more open science would always be the right decision. Yet the highest tenet of science is our reverence for the truth. Nuclear weapons and climate change have already proven that we do not live in such an idyllic world, and it would be irresponsible of us to pretend otherwise.

The primary reason that no terrorist has ever gained access to a nuclear device – or even the fissile materials required to create one – is that people of many nations recognized the proliferation threat and worked together to forestall it.(9) The resulting nuclear security measures did not prevent us from reaping the benefits of nuclear power: the International Atomic Energy Agency estimates that between 1971 and 2018, nuclear power plants prevented the emission of 74 gigatonnes of carbon dioxide, and continue to prevent an additional two gigatons per year.(10) Today, it’s unlikely that a naive observer would single out nuclear physics as an unusually unhealthy or unproductive field even though it has operated under security restrictions for many decades, and although working in climate science may be less comfortable now that the field has been politicised, accurate projections are arguably more important than ever.

Biology is no different. We can rationally assess the potential for misuse and take appropriate countermeasures without impeding beneficial advances; in fact, we have already done so. The advent of recombinant DNA in the 1970’s – i.e. the ability to cut and splice genes – provoked widespread concern that “there was an atomic bomb hidden away in modern biology.”(11) “Scientists were concerned that unfettered pursuit of this research might engender unforeseen and damaging consequences for human health and Earth’s ecosystems,”(12) leading them to declare a moratorium on their own research. Only after intense discussions at the famous Asilomar conference of 1975 did they correctly conclude that recombinant DNA within carefully chosen laboratory-adapted constructs posed no risk of spreading on its own.(13)

As nuclear fears receded with the end of the Cold War and the conclusions of Asilomar were confirmed, fears of “Andromeda strains” faded,(14) while assertions that “Nature is the greatest bioterrorist” – that humanity cannot match nature’s ability to generate novel agents capable of spreading on their own in the wild – became a cliché.(15) This claim may have been accurate as recently as a decade ago, but is now tenuous at best. For example, in 2013 I discovered CRISPR-based gene drive, a technology widely viewed to be capable of spreading genomic alterations made in laboratory organisms to entire wild species.(16) Gene drive systems, which can cause populations to collapse if not go extinct,(17) hold tremendous promise for eradicating diseases such as malaria and schistosomiasis, but the technology is accessible to individual researchers, who in principle are now capable of single-handedly altering Earth’s ecosystems. The remarkable acceleration of new advances in biotechnology over the past decade strongly suggests that other methods of building agents capable of exponential spread are also possible. Add ongoing attempts to deliberately engineer lethal viruses to become highly transmissible,(18) and asserting that humanity will not develop novel methods of engineering new pandemic-class agents appears to be dangerously overconfident.(19)

Nor does catastrophic misuse require novelty. Animal viruses manifestly do not spill over to cause pandemics in multiple airports simultaneously, and certainly not in groups, but once enough of them are identified, thousands of people will be capable of causing both.(20) If current trends continue, many such viruses will be made public: well-intentioned researchers at one agency currently seek to identify animal viruses capable of causing new pandemics, share their genome sequences with the world, and publish them in a list rank-ordered by threat level.(21) The security implications, which apparently went unrecognised by the relevant agency, its scientists, and even national security experts for over a dozen years, are ghastly.

A credible list of pandemic-capable viruses would in principle allow anyone capable of assembling those agents to seed so many outbreaks that even the harshest and most comprehensive of lockdowns by today’s nations would struggle to contain them all. With some natural viruses exhibiting the transmissibility of early variants of SARS-CoV-2 and a lethality rate exceeding 30 per cent,(22) such an event could precipitate the greatest catastrophe in the history of humanity. Even the best-prepared nations lack sufficient protective equipment for most key personnel, and vaccines and other medical countermeasures could not plausibly be manufactured and distributed in any time frame shorter than months, if they could be developed at all.(23) If essential workers are unwilling or unable to maintain food, water, and power distribution networks, societies will collapse.

This outcome is not inevitable, however, or even especially likely. But the same is true of a large-scale nuclear exchange, and of four degrees of climate warming: we cannot tolerate a tiny chance of any of them actually occurring. On this basis alone, we should approach the mitigation of global catastrophic biological risk with the same degree of seriousness as we do nuclear nonproliferation and climate change mitigation.

Below, I propose a set of interventions that, taken together, could plausibly solve this immense problem while negligibly impacting the lifesaving work of my colleagues in the life sciences. Technologies capable of effectively immunising nations against even adversarial releases of pandemic-class agents are now within our reach, and the price tag is a tiny fraction of existing defence budgets, let alone the cost of mitigating climate change. By delaying proliferation while we construct reliable systems for threat detection and defence, we can safeguard the international community from biological catastrophe.

1. Maroun et al., “Designing and Building Oncolytic Viruses”; Thi Nhu Thao et al., “Rapid Reconstruction of SARS-CoV-2 Using a Synthetic Genomics Platform.”

2. Lee, “Reverse Genetics of Influenza Virus”; Xie et al., “Engineering SARS-CoV-2 Using a Reverse Genetic System.”

3. Jackson et al., “The Accelerating Pace of Biotech Democratization.”

4. Carlson, “On DNA and Transistors”.

5. National Center for Science and Engineering Statistics, “Doctorate Recipients from U.S. Universities, 2019.”

6. OECD, “OECD: Graduates by Field.”

7. Diggans and Leproust, “Next Steps for Access to Safe, Secure DNA Synthesis.”

8. Diggans and Leproust. “Next Steps for Access to Safe, Secure DNA Synthesis.”

9. Hoffman, The Dead Hand: The Untold Story of the Cold War Arms Race and Its Dangerous Legacy.

10. International Atomic Energy Agency, “Climate Change and Nuclear Power 2020.”

11. McMaster, From Controversy to Cure - Inside the Cambridge Biotech Boom.

12. Berg and Singer, “The Recombinant DNA Controversy: Twenty Years Later.”

13. Berg et al., “Summary Statement of the Asilomar Conference on Recombinant DNA Molecules”; Berg and Singer, “The Recombinant DNA Controversy: Twenty Years Later”; Institute of Medicine (US) Committee to Study Decision Making and Hanna, Asilomar and Recombinant DNA: The End of the Beginning; Falkow Stanley, “The Lessons of Asilomar and the H5N1 ‘Affair’”; Grace, “The Asilomar Conference: A Case Study in Risk Mitigation.”

14. Berg and Singer, “The Recombinant DNA Controversy: Twenty Years Later.”

15. Oxford, “Nature’s Biological Weapon”; Watts, “Harnessing Mother Nature against Your Fellow Humans”; Clark, “The Ultimate Bioterrorist: Mother Nature!”; Reardon, “US Government Lifts Ban on Risky Pathogen Research”; Osterholm PhD MPH and Olshaker, Deadliest Enemy: Our War Against Killer Germs; Panosian Dunavan, “Uncomfortable Truths about Modern Epidemics: A Review of The Pandemic Century and Interview with Author Mark Honigsbaum”; Bakerlee, “Mother Nature Is Not the Ultimate Bioterrorist.”

16. Esvelt et al., “Concerning RNA-guided Gene Drives for the Alteration of Wild Populations”; Burt and Crisanti, “Gene Drive: Evolved and Synthetic”; Oye et al., “Biotechnology. Regulating Gene Drives”; Oye and Esvelt, “Gene Drives Raise Dual-Use Concerns—-Response”; DiCarlo et al., “Safeguarding CRISPRCas9 Gene Drives in Yeast.”

17. Eckhoff et al., “Impact of Mosquito Gene Drive on Malaria Elimination in a Computational Model with Explicit Spatial and Temporal Dynamics”; Beaghton, Beaghton, and Burt, “Gene Drive through a Landscape: Reaction-Diffusion Models of Population Suppression and Elimination by a Sex Ratio Distorter”; Beaghton and Burt, “Gene Drives and Population Persistence vs Elimination: The Impact of Spatial Structure and Inbreeding at Low Density”; Burt, “Site-Specific Selfish Genes as Tools for the Control and Genetic Engineering of Natural Populations”; Kyrou et al., “A CRISPR—Cas9 Gene Drive Targeting Doublesex Causes Complete Population Suppression in Caged Anopheles Gambiae Mosquitoes.”

18. Willman and Muller, “A Science in the Shadows”; Imai et al., “Experimental Adaptation of an Influenza H5 HA Confers Respiratory Droplet Transmission to a Reassortant H5 HA/H1N1 Virus in Ferrets”; Herfst et al., “Airborne Transmission of Influenza A/H5N1 Virus between Ferrets.”

19. Esvelt, “Inoculating Science against Potential Pandemics and Information Hazards.”

20. Esvelt, “Manipulating Viruses and Risking Pandemics Is Too Dangerous. It’s Time to Stop.”

21. Grange et al., “Ranking the Risk of Animal-to-Human Spillover for Newly Discovered Viruses.”

22. Thèves, Biagini, and Crubézy, “The Rediscovery of Smallpox.”

23. “American Pandemic Preparedness: Transforming Our Capabilities.”