Covid-19 shook the entire world to its core. What if it was deadlier?
On Earthquakes, Pandemics, and the Window of Opportunity
Why the current pandemic is a critical moment in infectious disease drug development reform
Despite the number of lives lost and the jaw-dropping economic cost the COVID-19 pandemic has inflicted upon our world, it is not unfair to say that the SARS-CoV-2 sized meteor ended up missing our planet by a few hundred thousand miles when compared to the impact of previous pandemics like the 1918 Flu. However, many of the conditions that facilitated this pandemic, such as the generational population shift to high-density urban areas, globalization, and many others, will remain going forward. Today’s preparation against future pandemics will be absolutely critical, but I worry that the steps needed to be taken to codify pandemic biodefense into a permanent part of the U.S. and global infrastructure will require a nuanced and far-reaching vision far beyond what will actually be instituted.
The biggest challenge to driving a truly meaningful and transformative effort will be the natural enemy of urgency: time. Human nature dictates that the public consciousness (and, therefore political will) lets black swan events fade from memory, and let other urgent matters take attention and funding away from non-urgent, but no less critical efforts — at least until the non-urgent becomes urgent again.
An excellent analogy is the history of California earthquake legislation, where legislative lulls are interrupted by frenzies of public policy initiatives following devastating earthquakes. This was punctuated by the famous 1989 Loma Prieta earthquake, where the relatively light consequences (62 lives and $10 billion in damage and business interruption) for a 6.9 magnitude earthquake during the 5 PM rush hour led to the most productive period for seismic-safety legislation in Californian history. A particular passage on page 35 is worth noting here:
“Current and former executive directors of the [California Seismic Safety] commission have mentioned a phenomenon they call the ‘window of opportunity.’ It is a period of time when the state’s policy-makers — the Legislature and the governor — are extremely receptive to moving forward on seismic-safety policy issues. The commission spends a great deal of its time amassing information and ideas on how to advance seismic-safety public policy. Having these ideas adopted is a painstaking process. When a ‘window of opportunity’ opens up, the process becomes much easier.”
While previous “windows of opportunity” like HIV, SARS, MERS, 2009 H1N1 Swine Flu, Zika, and Ebola failed to make a significant effort towards developing true pandemic response capabilities in the United States and the world beyond (a thought exercise would be to consider what would’ve happened if COVID-19’s lethality was significantly higher across all age groups), COVID-19 is less a window and more like the classic Buster Keaton stunt. It will be absolutely imperative that the COVID-19 window is where a major fundamental commitment to pandemic biodefense is made — anything less is admitting that we will simply never commit to any sort of prevention until we are hit by something much larger and devastating than COVID-19. An imperfect metaphor: If COVID-19 is the Loma Prieta earthquake, we really don’t want to wait for the Big One before making critical safety changes to our infrastructure¹.
After the crisis is over, national and international efforts will invariably establish post-mortem committees that will come to the conclusion that we simply need to re-arm our pandemic detection and prevention programs, replenish stockpiles of pandemic-related equipment, and an infusion of resources into the CDC and NIH for the next few years. There will be increased academic interest and there will be an uptick in virology and infectious diseases Ph.D.s for the next three to five application cycles, which will bolster interest in the infectious disease field and lead to the important groundwork that in theory will translate into new discoveries (which isn’t necessarily true — the antibiotic resistance field has seen a catastrophic collapse in innovation due to the lack of industry incentives that it only has begun to recover from, despite significant academic interest). Some may argue that that will be enough and that we’ve learned our lesson — that we will never forget about the risk of a pandemic again, and that the current government made it far worse than it needed to be. Admittedly, while this particular administration and current political climate may have facilitated the rise and continued spread of this pandemic, it is naive to consider that the current state of affairs will simply get better on their own or that the conditions that made this pandemic particularly devastating will never ever reoccur in the future. The time scales between black swan events can be long, and incremental progress requiring long-term sustained investment is often amongst the first to lose funding once the nationwide attention span shifts towards the next crisis. For example, the California medical stockpile established in 2006 was abandoned during the budget concerns in 2011. The most telling quote:
“ ‘When you’re stretched, prevention and readiness, future needs — unfortunately, that’s what gets cut,’ said state Sen. Richard Pan of Sacramento, chairman of the Senate Health Committee, who fought the cuts as a first-term assemblyman.”
While it will be critically important to continue these smaller long-term efforts like the maintenance of pandemic equipment stockpiles, they will always be at risk for as long as humans are unable to value the preparation for black swan events. The COVID-19 window will only be open for a finite amount of time.
The question, therefore, is what is the best way to take advantage of the significant political will generated by COVID-19 in the near term that will result in far-reaching effects in preventing pandemic-causing diseases?
Unfortunately, there is no simple answer to that question.
It is likely a huge number of initiatives, funding, and changes across the entire biomedical sector, many of which proposed in the book that inspired this essay, Biotechnology in the Time of COVID-19². These include a massive re-characterization program of approved therapeutics to better understand how they can be applied quickly and effectively towards a host of different potential outbreaks, the reimagining of FDA clinical trial process for times of emergency, cutting loopholes that allow insurance companies to make it harder to get tested and see a doctor, developing and furthering our diagnostic and telemedicine toolkits, and many more. However, one of the most interesting was touched on by Brook Byers in his entry, founding member of legendary venture capital firm Kleiner Perkins, in which he brings up the role of BARDA in the biotechnology industry going forward.
One of the most meaningful changes we as a country can make towards anti-infectious disease efforts is the significant and permanent broadening of BARDA and other related foreign government agencies’ role in aligning industry incentives to generate anti-infectious disease platforms, treatments, and therapeutics.
BARDA, or the Biomedical Advanced Research and Development Authority, is responsible for promoting the development of medical countermeasures against bioterrorism as well as pandemic-causing diseases. If properly funded beyond the paltry $1.6 billion per year provided before the pandemic (compared to other large government expenditures that have been touched on endlessly and will not be recapped here), BARDA and its peers have the potential to play a role in driving innovation in spaces where the unpredictability of significant outbreaks in their home countries may not provide enough financial incentive for private investors to fund innovation in the space.
An analogy of this is the antibiotic resistance field². Antibiotic resistance, where bacteria become resistant to conventional antibiotics over time thanks to evolution, was identified as a major looming problem for hospitals and other healthcare facilities. In response, the biotechnology industry developed new and better antibiotics, yet it turned out the warnings were too early.
Hospitals avoided buying these new and expensive drugs by using batteries of conventional, cheaper antibiotics, and the government, in hindsight shortsightedly, did not mandate that hospitals buy the upgraded ones in reserve or buy them up themselves. The massive financial losses the development of those drugs incurred, in turn, discouraged major pharmaceutical companies and investors from the space. This meant that small biotechnology companies, who could now neither expect acquisitions by Big Pharma nor profitability on their own terms, became innovation deserts, and money and talent quickly moved into more profitable areas.
Bacteria, however, didn’t magically stop evolving, and we eventually came to realize that the next generation was going to be desperately needed, leading to the expansion of programs like BARDA that helped fund new antibiotic resistance research. However, as anyone in the life science industry will tell you, innovation is like getting on a bike with your hands tied behind your back and pedaling: it’s much easier if you’re already on it and have some momentum as opposed to starting from the bike lying on the ground.
Infectious, potentially pandemic-causing diseases are a significantly more extreme example
As opposed to antibiotic resistance, which was a slowly growing but predictable problem, infectious diseases in developed countries are unpredictable and highly differentiated in scope, transmission, mechanisms, and effect. Their unpredictability, heterogeneity, and prevalence in poorer countries make the financial incentives to create meaningful innovation through anti-infectious disease platforms, treatments, and therapeutics difficult to justify and therefore not a massive concern — until they are.
Even incredibly hyped companies like the Bill and Melinda Gates Foundation and ARCH Venture-backed VIR Biotechnology struggled to draw public investment pre-COVID, though these platform-based approaches will now be excellent test cases in their ability to develop new therapeutics quickly and effectively.
In the meantime, it is up to the governments of wealthy countries to provide financial incentives for small biotechnology companies to develop innovative approaches against infectious diseases by providing themselves as their initial customers. This would have the additional benefit of furthering the research that could change millions of lives in countries that struggle with infectious disease, along with shoring up our own biosecurity and providing other political advantages, such as the greatest medical diplomacy program in the world.
Some may argue to expand the roles of the NIH and CDC, along with BARDA’s DRIVe program, to do these functions themselves. These organizations, however, are not known for their ability to bring new therapies to market and a task such as this is significantly beyond the scope of their capabilities and their current infrastructure. Therefore, if we agree that the expansion of BARDA route is the most feasible and logical, a lot of interesting questions can be asked, such as:
What level of government commitment would be needed to drive innovation in the space and truly become an interesting opportunity for investors?
What particular set/style of companies and size/timing of grants would best fit for this sort of structure, and what level of alignment needs to exist between the government/company/investors for an undertaking like this one to be successful?
These questions will have to be approached carefully, thoughtfully, and with significant input from all related parties to ensure we make the best possible decisions for our future while our window of opportunity is still open. The COVID-19 pandemic is a wake-up call that opened a (hopefully) once-in-a-lifetime window of opportunity. Let’s make sure to take full advantage before the next one tears the foundation down completely.
Merouane is a Masters of Arts in Biotechnology student at Columbia University. He intends on pursuing a career in life science investing and hopes to contribute to the field through rigorous and fundamentals-focused analysis of biotechnology companies and landscapes. You can find him on Twitter @merobiotech.
- I say imperfect because COVID-19 is more like the Loma Prieta and Northridge earthquakes combined. The Loma Prieta Earthquake led to record amounts of earthquake legislation and Northridge demonstrated the necessity of protecting affected Californians from the economic devastation of major earthquakes.
- This is a truly excellent book consisting of various entries from a wide breadth of different points of view, and anyone interested in the biotechnology industry’s perspective on COVID-19 should give it a read. Some of my favorites are from Mark Lampert, Geoffrey Porges, and Peter Kolchinsky, but all are definitely worth your time.
- See Peter Kolchinsky’s “The Special Case of Antibiotics” in his book, The Great American Drug Deal.
