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Monday, October 02, 2023
Students take part in an in-person Microbiology 304: Biology of Microorganisms lab session taught by Jon Roll, faculty associate in the Department of Bacteriology, inside the Microbial Sciences Building at the University of Wisconsin-Madison on April 22, 2021. All people physically present were wearing a face mask and practicing physical-distance safety protocols as the coronavirus (COVID-19) global pandemic continues. (Photo by Bryce Richter / UW-Madison)

The next COVID-19 could be so much worse

The hospitals shut down within days. No one shows up to work anymore, and no one could blame them in light of the awful, unnamed virus spreading everywhere. The crucial supply chains – for protective gear, for food, for gas, for everything — were also crippled. Hardly anyone is leaving their house, and those that do encounter apocalyptic scenes. 

The culprit? A deadly pathogen. But not just any pathogen, a man-made, engineered pathogen. A pathogen designed to kill as many people as possible.

Unfortunately, this terrifying hypothetical is not hypothetical enough. Emerging biosynthetic technology holds the power to wipe out our species — a power previously reserved to only a select few world leaders with access to huge nuclear arsenals. The threat of man-made pandemics needs to be seriously addressed.

COVID-19 was and continues to be a trying hardship for everyone, no doubt, but it could have been worse. It had a mortality rate of around 2.3% and a transmissibility rate (R0) estimated at around 2.4%. In nature, these viral attributes play out in a game of genetic trade-offs. A virus with a higher death rate might kill its host before they pass it on, in which case it is hard for that virus to spread to other hosts. Other viruses may spread rapidly but affect their hosts less severely. A natural virus could undoubtedly have a constellation of attributes that make it worse than COVID-19, but its deadly impact is evolutionarily constrained. 

These constraints do not exist on engineered pathogens — pathogens fine-tuned to kill. For example, an existing pathogen with a mortality rate of over 50% could be modified to have a much higher transmission rate. 

Indeed, this already happened. In 2012, researchers in the Netherlands and here at the University of Wisconsin-Madison used animal models to genetically modify H5N1, an influenza strain with a mortality rate of around 60%, to spread far easier. It worked. A virus that could previously only spread by touching or handling infected poultry could now spread through droplets. 

The U.S. National Science Advisory Board for Biosecurity candidly stated that the release of this virus would be an “unimaginable catastrophe for which the world is currently inadequately prepared.”

This modification serves as a testament to the fact that the technology to engineer a viral killing machine already exists.  Worse yet, as bad as this constructed contagion is, it is not even an upper bound. A virus could, in principle, have an even higher death rate combined with an asymptomatic period of a month or longer, allowing it to diffuse globally before even the first detection. Our capacity to imagine just how bad an engineered pandemic could get is highly constrained. 

Synthetic viruses are no longer science fiction — they’re a reality. The increasing democratization of who could design such a virus — and how easily — requires us to dramatically rethink what we are going to do about it.

The field of synthetic biology has undergone exponential growth in recent decades. What would have been unimaginable years ago is commonplace now. For example, the Human Genome Project cost around $3 billion and took 13 years. Today, you can get your own full genome for $300 — free shipping included. 

Similar exponential advances have occurred in the technology that made the modification of H5N1 possible. The rate of progress in synthetic biology shows no signs of stopping, so it is logical that there will be new advances we can hardly imagine today (e.g. DNA printers). Knowledge and technology currently localized at the field’s frontier will become more and more democratized. 

We must not allow this democratization to happen. On the current course, the population of people capable of creating and releasing a deadly pathogen will eventually overlap with the population of people who would release a deadly pathogen given the opportunity. 

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And who would want to release such a deadly pathogen? History shows that there are several possible motives. Take suicidal mass murderers, doomsday cults, and radical environmentalists as examples. The death count stemming from people who want to kill others is typically constrained by how such people can kill others (e.g. pistol vs. automatic weapon vs. jumbo jet). The current rate of progress and democratization in synthetic biology would remove almost all constraints.

Pathogens built with malicious intent have been the primary focus so far, but those modified in the name of science — like the H5N1 modification discussed earlier — pose risks too. Modifying an existing pathogen to increase its functioning is known as “gain-of-function” research. A long history of pathogens escaping labs exposes the dangers of storing super-pathogens, like those made with gain-of-function research.

There are examples of both unintentional and intentional lab leaks. Back in 1978, a year after smallpox was effectively eradicated, lab-stored smallpox virus escaped in the UK, infecting two and killing one. The last person to die from the disease that killed more than 500 million people in its last 100 years died from a lab outbreak. It is a chilling tale of surprisingly common laboratory escapes, even from labs with Biosafety Level 4, the highest possible international safety standards.

Some evidence suggests COVID-19 may also have come from a lab leak, although there is debate about this evidence and whether the research in Wuhan counts as gain-of-function research

There are also examples of lab pathogens being intentionally weaponized. In 2001, Anthrax tracing back to the Department of Defense's lead laboratory was used in a bioterrorist attack that killed 5 and sickened 17. Essentially, storing lots of pathogenic death is bound to kill.

So what should be done about the risks posed by engineered pathogens?

With respect to gain-of-function research, the answer is straightforward: this dangerous research should be banned. While there is some theoretical value in understanding how these viruses behave, it is (1) unlikely that a virus in nature would ever be as bad as what can be created in these labs, and (2) any potential value is outweighed by the proven possibility of a leak, intentional or not. 

With respect to reducing the risk of a malicious actor engineering a pandemic, the answer is more complex. We need to build a “global immune system,” in the words and ideas of Rob Reid, a leading thinker on the danger of engineered pandemics. 

This global immune system needs to be multi-faceted. It needs to make the synthetic biology infrastructure harder to hijack, survey for possible outbreaks and ready society to deal with an outbreak at any stage. 

There are promising policies and technologies at each of these stages. To make synthetic biology infrastructure harder to hijack, we can mandate the current work of the International Gene Synthesis Consortium (IGSC), creating global regulations on monitoring all DNA prints and comparing them against a list of known pathogens. 

To survey for possible outbreaks, we can get creative with online symptom search scanning, wastewater testing and promising new detection systems. To prepare society for an outbreak, we can work on universal flu vaccines, distribute personal PPE stockpiles and improve our vaccination pipeline.

These are only a fraction of the countermeasures already being discussed. The ideas and technologies are there, but two really important things are missing: money and attention. As a prerequisite, the need for the global immune system must be recognized and funded.

Funding all these countermeasures won’t be cheap, but it is an investment that will pay itself off. This is especially true since many investments, like improved outbreak detection, are applicable to engineered and natural viruses. And we know natural viruses are inevitable, especially as humans relentlessly encroach on wildlife

Consider the cost of COVID-19. COVID-19 killed more than 4,790,000 people, and counting, and estimates predict it will cost $80 trillion globally. Funding countermeasures may pose high upfront expenditures, but these costs will be more than covered in mitigating deadly (and costly) viruses. 

As highlighted in the United States budget — allocating $634 billion on nuclear deterrence from 2021 to 2030 — there is a strong precedent to fund countermeasures to prevent the possibility of something really bad happening. Engineered pandemics epitomize a global security threat, similar to nuclear weapons, and should be funded accordingly.

Nevertheless, inaction towards collective, intergenerational problems like climate change demonstrates society’s dangerous disposition to not fund some problems according to the threat they pose. For the betterment of our society, this must change, especially in regards to engineered pandemics. 

As a society, we must wake up to this danger. We must turn the tragedy of COVID-19 into a lesson for the future. The reality is that COVID-19 may have been a dress rehearsal for a worse natural pandemic. Yet an engineered pandemic would make a worse natural pandemic look like a puppet show. We have difficulty grasping these orders of magnitude, but let us not let that translate to difficulty acting upon them.

Michel Justen is a senior studying Neurobiology and Psychology and President of Effective Altruism UW–Madison. Lenni Justen, his twin, is a senior studying Physics and Political Science and an intern at the Office of the Director of National Intelligence researching biosecurity. Do you agree with the need to better prepare for a future with engineered pandemics? Send all comments to

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