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Human Health, Innovation

Mutually Assured Protection

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How to prepare for the next inevitable pandemic and limit the impact of infectious diseases.

No health crisis was more predictable than the COVID-19 pandemic. Indeed, it was comprehensively predicted: by Bill Gates in 2015, by President Obama’s Homeland Security and Counterterrorism Adviser in 2017, and by many others, over several decades. Some nations were ready. Governments in Singapore, Taiwan, Hong Kong, South Korea, New Zealand, Germany, and Canada implemented the standard public health response to pandemics: mass testing and contact tracing of the infectious, followed by quarantine of those thought to be shedding the virus and of vulnerable groups.

That some nations did control the spread of the virus—at least in its early stages—is proof that catastrophe was avoidable. But even those countries where public health measures limited the spread of the coronavirus, citizens remain vulnerable to contagion. Nor, in coming years, will every nation enjoy the leadership, resources, or luck to beat back every new threat. We lack a global mechanism to guard against future pandemics: a health security system emphasizing prevention, early detection, and characterization of emerging pathogen threats; rapid deployment of highly targeted protective interventions; and the development of effective treatments. But health security should do more than protect humans against pandemics. Infectious diseases of every kind continue to be a burden in rich and poor countries in their impact on health, happiness, and economic productivity. Humanity needs a global response to pathogens, analogous to the alliances that protect us against other threats such as nuclear war and famines.

The imperative to develop a shield against pathogens should be uncontroversial. New, potentially epidemic or pandemic pathogens arise at consistent rates. The 20 years preceding the SARS-CoV2 crisis saw a steady march of outbreaks: Nipah in 2001, SARS in 2002, H1N1 swine flu in 2009, MERS in 2012, Ebola in 2014, Zika in 2015, and many other less well known viruses. Major influenza pandemics have circled the world four times since 1918. Even in an ordinary year, seasonal flu kills 250,000 to 650,000 people. Malaria and tuberculosis are together responsible for nearly two million deaths per year. Sepsis, a dangerous but treatable body-wide response to viral, bacterial, fungal, or parasitic infection, is involved in up to 20 percent of annual deaths worldwide. Mosquito-borne malaria is thought to have killed 4 to 5 percent of all humans who have ever lived. More, there is growing awareness that infections can incite other chronic and life-threatening problems, from cancer to depression to neurodegeneration.

COVID-19, which blanketed the planet in a mere 100 days, demonstrated how far and how fast new viruses can spread in the era of global commerce and consumer jet travel. But the pandemic should have come as a challenge for which we were prepared, not a surprise that it took more than a million lives within just a few months and crashed the global economy. Biologists and public health experts know that as viruses mutate and evolve in animals such as bats, swine, and birds, they will spill over into humans: The only unknowns are the contagiousness and deadliness of zoonotic strains. It is sobering to reflect that the virus responsible for COVID-19 is comparatively benign. If the current pandemic had instead been caused by a virus with the case fatality rate of MERS and the contagiousness of measles, we would by now almost certainly have seen a global death toll in the hundreds of millions, and the collapse of many national economies. One of the primary purposes of such a health security effort would be to anticipate such threats before they emerge and spread unchecked—and then deploy immediate interventions to the right people in time to limit sickness and suffering.

In theory, these functions should be the responsibility of the World Health Organization. But international public health programs have never been adequately resourced or empowered. Preventing COVID-19 “was very possible—but we didn’t do it,” observes Peter Daszak, chairman of the Forum on Microbial Threats at the National Academies of Sciences, Engineering, and Medicine. “Governments thought it was too expensive.… And the W.H.O. … had neither the funding nor the power to enforce the large-scale global collaboration necessary to combat it.”

An effective response to pathogens will prepare for the next pandemic and limit the impact of other infectious diseases, helping turn sick-care into healthcare. But such a project will require businesses and ordinary citizens around the world demand and contribute to significant investments by governments and healthcare systems. More, decision-makers and stakeholders will need to align around this global effort in an unprecedented spirit of cooperation, guided by a clear set of scientific and technical strategies and governing principles.

Strategies for responding to pathogens

(1) The first priority is enhanced pathogen discovery and surveillance. The identification of the viral pneumonia later designated COVID-19 was announced on December 31, 2019, by the Municipal Health Commission of Wuhan, the Chinese city where the virus jumped from animals to humans. But Wuhan did not enter lockdown until January 23—far too late to prevent travel by infected individuals to other cities. Indeed, recent evidence suggests that the virus had already spread well beyond China and the last quarter of 2019.

The next pandemic virus likely already exists in an animal reservoir or human host. Scientists know HIV was present in humans as early as the 1950s, and the same may be true of many pathogens considered newer threats. We should develop capabilities to sample these viruses, sequence their genomes, and build new computational models to explore evolutionary trajectories, characterize mechanisms of pathogenesis, and identify high-risk scenarios. We could then complement these discovery tools with information technologies that spot and monitor actual and potential pathogen outbreaks as they emerge. Nations already collect some of the surveillance data that might mitigate pathogen threats, including information on everything from livestock market trends to cell phone movement patterns. But that data needs to be put to better use and combined with insights from new, purpose-designed technologies. Ultimately, we will want much of this data to be transparently shared and integrated into public health decision-making.

(2) Armed with better data and models, the world should also engage in pathogen control, in the tradition of wildlife or forest management, in order to minimize the opportunity for people to be widely infected. Such pre-prevention approaches could include tracking and control of pathogen reservoir species; novel sterilization techniques similar to the trial release of genetically modified mosquitoes to limit the spread yellow fever, dengue, and Zika; or the widespread installation of building-scale protective equipment such as next-generation air filtration systems.

(3) Because some pathogens will overcome even the best precautions, humanity must preemptively prepare to treat infected populations. The third strategy, therefore, should be to create what Noubar Afeyan, the CEO and founder of Flagship Pioneering, has described elsewhere as a capability “primed to develop new treatments and vaccines against novel diseases and deploy them at scale.” Rapid response will not be enough: We need to go beyond being rapid to being pre-armed with the necessary knowledge, and beyond response to readiness. The term instant protection best describes the goal for which we should strive: the construction of a standing research and production pipeline so that new vaccines, antibodies, antivirals, antibiotics, and other agents can be deployed as soon as possible after an outbreak or new pathogen strain emerges. Instant protection would also include the development and stockpiling of interventions that might act as firewalls to slow the spread of pathogens through vulnerable and high-risk populations. AI and machine learning can aid in rapid intervention discovery and development, and agile manufacturing and delivery networks can help with the distribution of vaccines as well as personal protective equipment, sterile glass vials, syringes, and other medical supplies.

(4) Because many pathogens can have highly damaging effects on their hosts for weeks, months or even years after the acute infection has subsided, one final strategy should be long-term mitigation to monitor individuals for disease risk and prior infection and provide suitable protective or therapeutic solutions. As an example, COVID-19 has proven to be a complex multisystem disease with devastating long-term health consequences—many of which we are only beginning to realize. Integral to a worldwide effort to respond to pathogens, therefore, will be technologies to establish and address the vulnerability of individuals and specific groups to these impacts.

Implementing all of these strategies may call for entirely new models of healthcare delivery and international cooperation. As one possible example, it may be necessary to create an international force of healthkeepers, trained in primary care and epidemiology and prepared for rapid international deployment, analogous to armed United Nations peacekeeping forces. These front-line fighters would help local healthcare professionals when required, and they would also gather data and coordinate with public health agencies to look for patterns and tactics to stem a pathogen’s spread. Imagine the impact of an international body of healthkeepers collecting and sharing real-time data from Chinese, Italian, and U.S. clinics in January 2020.

Principles for action against pathogens

Before any strategies for a pathogen response can be implemented, societies will have to agree on a few basic principles for addressing infectious diseases.

The first and most obvious principle is that a global effort must be truly global. During the COVID-19 pandemic, government responses have ranged from swift containment to denial and delay. But whether effective or disastrous, the responses were mostly national. A patchwork of responses allows novel viruses to spread rapidly. Because we live in a global society, we must learn to work collectively; advocates from industry, NGOs, foundations, academia, and patients’ groups must lean on national leaders to cooperate with other governments. Such an effort should be global in another sense: It must address most pathogen threats—not only those with pandemic potential—and encompass every aspect of pathogen defense, from the discovery of new pathogens to the mitigation of chronic health effects associated with infection.

Next, one way to fund an international effort of this importance will be through public investment. Traditional markets lack the incentives to invest in the development, testing, and deployment of systems for pandemic prevention and response. Early in the coronavirus pandemic, world leaders committed around $8 billion for development and deployment of diagnostics, vaccines, and other treatments, but this spending was restricted to COVID-19, and the U.S. did not participate. In place of this reactive and limited approach, health security will require predictable, long-term public funding, with nations investing on their citizens’ behalf in the same way that employers invest to protect the health and productivity of their employees. This is not to say that new private sector reimbursement will not emerge. Part of any global response to pathogens will involve the design and implementation of new business models and associated incentives.

Finally, as we design and build new institutions and processes to fight pathogens, we should adopt a systems view of risk and mimic the defense-in-depth strategy used by high-reliability organizations such as nuclear power plant operators and aircraft carrier crews. Like most large-scale disasters, the catastrophic U.S. response to COVID-19 cannot be traced to a single failure but to a cascade of them. Psychologist James Reason at the University of Manchester, in the U.K., suggests viewing health security as a series of “slices of Swiss cheese” where failures are anticipated but are contained by additional layers of risk mitigation. The first cases of a virus might be detected too late, contact tracing might miss superspreaders, or vaccines might take longer to develop than hoped, but other layers in the system would check and contain these failures. So long as the “holes in the cheese” are not aligned, catastrophe is avoided. “The basic premise in the system approach is that humans are fallible, and errors are to be expected, even in the best organizations,” James Reason writes. In 2020, public health officials have relearned this lesson the hard way.

Flagship Pioneering is actively working to create breakthroughs and build first-in-category companies across every major area described above—starting with Global Pathogen Shield discovery, early warning, and instant protection tools and approaches. According to Noubar Afeyan, “The threat posed by pathogens is to all humanity, not just to a country here and a country there.” It’s time to implement global strategies that will provide broader, more robust defenses than ever before against the scourge of infectious disease.

Story By

Lovisa Afzelius

Lovisa Afzelius is an origination partner at Flagship Pioneering and leads one of Flagship’s Business Units. A computational scientist by training, she brings to Flagship two decades of leadership experience and a passion for data-driven drug…

Alex Goldsmith

Alex Goldsmith joined Flagship Pioneering in 2017 as Principal to Noubar Afeyan, the firm’s CEO. Since 2020 he has focused exclusively on company creation, and currently forms part of the Origination team led by Lovisa Afzelius. His particular…

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