Part I: Why Biosecurity Matters – What are We Protecting Against?

Part I: Why Biosecurity Matters – What are We Protecting Against?

Pandemics have killed an estimated 230-400M people in modern human history, with COVID killing an estimated 27M in four years. The Bubonic plague wiped out 17-22% of humanity off the face of the earth while the Columbian Exchange wiped out 90% of exposed native populations. Indeed, the death toll from pandemics isn’t far off from that of all wars. Adding in deaths from infectious diseases broadly and the inter-human disease transmission dwarfs that of violence. In fact, it’s among the leading causes of death of all time. 

The threat of pandemics will only rise. Global economic integration and travel make the world-wide dissemination of pandemics inevitable and near-immediate. Even more importantly, the dual-use nature of biology makes pandemics themselves more likely as our power to understand and control biology continues to grow nonlinearly and access to that power becomes more democratized. 

The reason for concern ranges widely from preventing intentional bioterror to simply making our workplaces less prone to transmitting the common cold. 

Assessing the likelihood of a major bioterror event falls prey to the difficulty of predicting any black swan or fat-tailed event; however, it’s clearly non-negligible and unacceptably high. While 183 states are committed to the Biological Weapons Convention, multiple states are alleged to have violated it and at least three state actors are known to have used them before its signing in 1971, including the Soviet Union engineering and accidentally releasing an enhanced smallpox from its biological weapons division. 

Meanwhile, non-state actors from Al-Qaeda, to an esteemed scientist at a US military lab with security clearance, to a cult leader trained at a Kyoto graduate school in virology and genetic engineering have tried to acquire and use biological weapons, with the latter two being reasonably effective. In total, as of 2000, there had been 27 cases where a terrorist attempted to acquire or use such an agent and 8 cases where they successfully acquired one. 

Understanding The Implications of Biosecurity

More worrying than historical base rates is the scale of devastation possible, the ongoing vulnerability to such an attack given the publicly available information, and the relative technical ease of putting it to use. 

Whereas nuclear weapons are protected by military units, information to construct pathogens capable of killing similar numbers of people are published freely online. The world’s epidemiologists and virologists spend their lives studying pathogens’ inner workings and publish the work in scientific journals. The genomes of all viruses and the step-by-step procedures to boot them up are freely available. The intent is of course purely noble – to arm their colleagues with the knowledge to defeat ongoing viral threats and be better prepared for future ones. However, this body of work also makes it easy for anyone with graduate-level training to use it malevolently. Roughly 30,000 virology PhDs around the world have such capabilities. 

Multiple researchers have exhibited the ease of reconstructing a dangerous virus. Canadian virologists ordered DNA fragments of the extinct horsepox virus from the internet for $100K, diligently assembled them, and then demonstrated the resulting virus’s ability to infect cells and reproduce. 

As another example, the complete coding sequences of all eight viral RNA segments of the 1918 Spanish influenza that killed 20-40 million people was determined, and researchers later reconstructed it using reverse genetics and observed that it “exhibited exceptional virulence in the model systems examined and that the 1918 hemagglutinin and polymerase genes were essential for optimal virulence.” Other groups have synthesized Ebola, polio, smallpox, etc.

Luckily, none of them pose a threat, because they’re all well understood and therefore readily treatable. For many, we have vaccines stockpiled. The concern is that a new virus emerges and humanity follows its normal protocol of posting the sequence online, adding it to the publicly available rank-ordered list of the most deadly emerging pathogens, and publishing studies on how exactly it works. Then, a malevolent actor orders the DNA, synthesizes it, and releases it at many major airport hubs around the globe, simultaneously. 

The Omicron variant arose in Southern Africa and within a hundred days of its sequencing had infected a quarter of Americans and nearly half of Europe. How much faster would it have been if it happened to originate in NYC or, in the case of bioterrorism, if it was purposely released at multiple airport hubs from the start? 

While everything mentioned above is purely about naturally occurring viruses, we’re increasingly able to improve upon Mother Nature’s work, for both good and bad. Gain of function research aims to enhance microorganism functionalities, rapidly improving AI models can be used to make pathogens more dangerous and / or harder to detect, people are making DIY desktop DNA printers with instructions for how to assemble one yourself. Whether such engineered viruses leak from a top lab or the tools become so powerful and easily accessible that someone like the Unabomber – a Berkeley math professor – can figure out how to harness them, the threat from engineered viruses will only rise as we progress through the Century of Biology.

The worst case scenario is a virus with high lethality, highly contagious, and a long vesting period. 

Imagine a more lethal, airborne version of HIV: it spreads fast with 50%+ lethality but you don’t feel sick for over a year. That way, the whole world could become infected without realizing it. Without an overhaul of our physical infrastructure and stockpiles of preventative care with safety far beyond that of N95 masks for essential workers, that could be a truly existential threat to humanity – one far more deadly than an all out nuclear war.

Finally, whereas all of the above covers low probability, extreme outcome scenarios, the need for an overhaul of our physical infrastructure extends all the way to the high probability, low impact scenarios of daily life. We tolerate airborne illnesses like the common cold and the flu enabled by our lack of indoor air cleaning infrastructure, yet these cause hundreds of millions of sick days a year and double-digit billions of dollars in direct healthcare costs and lost wages. Moreover, some studies show material improvements in productivity from just getting rid of stuffy (i.e. CO2-rich) air. 

Note that we focus on indoor air cleanliness because that’s where transmission generally occurs – particularly for respiratory diseases. An estimated 90%+ of Covid infections occurred indoors.

We used to tolerate unclean water as well – until a critical mass of death and discomfort with the smell forced change. London’s main source of drinking water – the Thames – used to be near-opaque with waste of all kinds. The sewage marinating in the city’s drinking water caused recurrent waterborne disease outbreaks. In the mid-1800s, a series of cholera outbreaks killed hundreds of thousands. That, combined with a stench so palpable that “the feculence rolled up in clouds so dense that they were visible at the surface,” led to physicians and statisticians teaming up to figure out that the incidence of cholera clustered around a single water pump. 

Building a modern sewage system added decades to Londoner’s life expectancy. As the world integrated that wisdom, the beginning of the end to waterborne disease was marked. It has saved at least 130 million lives in just the last 50 years alone. 

It’s time to do the same for airborne diseases. 

Relegating the threat of pandemics and the common cold to the history books requires a range of initiatives from prevention to post-infection. It’s an exciting problem set for startups and for new science. 

Biosecurity’s Venture Scalability

In discussing biosecurity, many push back on the venture-scalability of a for-profit entity as opposed to government or non-profit-run common goods. First, the government has moved at a glacial pace in this space, not using the most up-to-date technologies or sophisticated methods and not expanding even remotely as rapidly as is required. For instance, while the government scans for pathogens, it only does so for a few dozen well-known ones and hasn’t updated the list in decades. Proper threat monitoring would update sequence and pathogen lists by the second. 

As for the market opportunity, the awareness of the threat that biology can pose following Covid-19 gives a perfect chance to build our defenses to prevent and mitigate the next one. In addition to the 27M lives lost, it wrecked economic destruction to the tunes of tens of trillions of dollars. 

And yet, despite the dramatic uptick in scientific and entrepreneurial efforts to prepare, we believe there remains a severe fundamental underpricing of risk. The odds of pandemics are only rising given the increase in power and democratization of biotech, global geopolitical hostility, and global interconnection.

Biosecurity as a % of Spend

One way to think about the biosecurity market is as a percentage of the spend in the areas biology touches: biotech and agriculture. Companies will spend a small percentage of revenue on biosecurity to protect against the liability of causing an outbreak and to invest in their customers’ trust – people will not want to eat a lettuce brand associated with a pandemic while a biosecurity event related to a cell therapy company would be its bitter end. 

Companies spend 0.2-2% of revenue on cybersecurity depending on the threat it poses to the business. We expect a similar range for biotech / pharma, healthcare providers, and agriculture as the biosecurity market matures, with some subsectors like agriculture supply chain, factory farms, hospitals, biomanufacturing, and synthetic biology being on the higher end. These are multi-trillion dollar markets, which yields a large opportunity for cutting edge biosecurity providers.

As there begins to be more of a framework for how liability is quantified and passed down to industries from governments, these build vs. buy decisions may only become more valuable.

Put simply, unknown markets being unquantifiable doesn’t mean they’re small. 

Biosecurity: The Market for Trust In and Safety from Our Biotechnology Innovations

Our ability to understand, control, and engineer biology is becoming stronger and more democratized at a nonlinear rate. Specifically, the convergence of increased biological legibility through LLMs (even if GPT-4 isn't deemed good enough yet), high throughput engineering through better molecular tools (CRISPR, MoClo kits, cheaper sequencing), and better predictability of biological processes creates exponentially more risk than in prior decades that bad actors could synthesize a pathogen, enhance it, or make an entirely new one.

Moreover, the increasing ubiquity of bioengineering and biomanufacturing to produce ever-more of our food, commodities, and goods further expands the threat surface for natural outbreaks and bad actors. 

Considering all this, where would you expect the market for trust in and safety from our bio-based innovations to go from its current, minuscule base? 

We will expand on this sentiment in Part II of this post to be published soon where we break down our views on the highest priority problems to be solved, the current and possible future suites of solutions, and where we’re most excited about helping build a company. 

Crucially, early movers in biosecurity will set the stage given the government’s slowness and the lack of current alternatives.