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As the new coronavirus began seeping through national borders three years ago, government responses varied wildly. Some issued travel bans. Others ordered complete lockdowns. Some suggested residents keep to themselves and wear masks when they couldn’t. Other nations urged the young and healthy to go about business as usual, in the hopes that enough infections would quickly lead to herd immunity.
Individual responses were just as varied in as much as they were allowed. Some people isolated at home, adopting virtual technologies for socializing, conducting business, receiving medical care, and learning. Others made masking a new norm whenever they ventured out. Some who could moved to the country, changed jobs, or created social pods. Still others defiantly carried on as usual, determined to not change their behavior in the face of the new threat. Most everyone put down their stakes, while death counts mounted around the globe, convinced that their reaction was the correct reaction.
Defense is simply hard.
Despite these varied responses, hundreds of millions of people have been infected, many millions have died, and many more are living with long-term health consequences. Why was finding an effective response so hard?
There are many reasons why we—collectively and individually—found it so difficult to respond effectively to the arrival of a novel coronavirus. It took time to learn how the virus spread, leaders had to balance public health with economic health. And individuals were bombarded with shifting—and sometimes conflicting—messages.
But there is another fundamental challenge. Defense is simply hard, whether it is devising public health responses to a pandemic, protecting a business against ransomware cyberattacks, or securing a border against hostile incursions.
We aren’t, of course, the first ones to face harmful—even existential—threats. The mounting of attacks and defenses is a dance as old as life on our planet. And the choreography is logged deep within life’s immune systems. The immune system of something like the flatworm has had nearly 840 million years to evolve. Those time spans allowed for nearly incalculable attempts at experimenting, rejecting, tweaking, and innovating to combat diverse and wily foes.
Fortunately human engineers needn’t wait for evolution by natural selection to change strategies—they can experiment and innovate in real time. By shaping defense strategies to follow immune dynamics, we can find useful models that could help save us from future assaults.
From deception to collateral damage, immune systems are constantly monitoring, adapting, and executing energetically economic strategies. Here are seven central challenges of defense—and ways the immune system can show us a path forward to keeping us safer in the future, regardless of the foe.
Deception: Stealthy attackers may be nearly indistinguishable from parts of their target, evading detection through mimicry, disguise, camouflage, or outright deception. Infectious pathogens may evolve to closely resemble their hosts (or at least cells within their hosts), spies blend in with the communities they are targeting, and phishing attacks pose as innocuous emails. Designing a detection system to discriminate accurately between “self” and “other” requires that system to be extremely precise in order to avoid making mistakes and either missing some attacks—or overcorrecting and harming the self.
Autoimmunity: Defending a system of any significant complexity almost always runs the risk of mistaken identity, where the response is directed against a part of the system itself. We are learning that an ever-increasing array of human diseases—celiac disease, Type 1 diabetes, rheumatoid arthritis—are at root autoimmune issues. Similarly, accidental friendly fire is a known problem in war; spam folders can delete legitimate emails; and professional home service people can be mistaken for intruders.
The immune system of something like the flatworm has had nearly 840 million years to evolve.
Ambiguity: In many cases perfect detection is impossible due to inherent ambiguities. Reliable citizens may be turned by foreign operatives, information that is harmless in one context may be misleading in another, and the so-called “fog of war” can increase the odds of friendly fire.
Threshold: Many threats are tolerable at low levels but dangerous when they rise above a threshold. A couple of mistyped password attempts might be understood as an unintentional error while 100 such attempts might be interpreted as a password cracking attempt. Deciding where to set such thresholds not only impacts defensive effectiveness, but also its cost—if we deploy resources every time there is even a minor threat, defensive expenditures (be they measured in time, money, or energy) can become prohibitive.
Collateral damage: Defensive systems need to avoid making the cure worse than the disease. During the early months of the COVID-19 pandemic, many of us learned for the first time about “cytokine storms”—life-threatening systemic inflammation driven by an overzealous immune response to the virus. A successful defense system must, as much as possible, deploy a proportional response—one that does not cause more damage than the original threat.
Completeness: A detection system that is precise enough to avoid autoimmunity while still detecting nearly all attacks is resource-expensive. For example, it’s not economically feasible to search every square inch of every import arriving on a country’s shores for potential invasive species. But it is also not economically wise to forego all invasive species searches. The challenge lies in figuring out what level of completeness works best for the situation.
Enemy evolution: Adaptation, evolution, and innovation allow attackers to discover weaknesses and vulnerabilities in a defense system, enabling them to stay one step ahead of a defense system. Attackers also often adapt their strategies through time. Some viruses, for example, become less virulent as they spread through a population, in order to avoid killing their hosts before they can infect more individuals.
Given the many challenges of defense—against the global spread of pathogens, invasive species, computer scammers, invading armies—it’s unlikely that any single defense tactic can be perfect. But that doesn’t mean we should give up trying to improve. Which is where we can borrow more tactics from the accumulated wisdom of evolved immune systems.
First, we can be adaptive. One feature of the COVID-19 pandemic was the frustration associated with changing advice. But advice always changes as knowledge or technology improves. The best ways to defend a house in the 1960s are not the best ways to defend it today. New technologies render the old less useful. Advice on personal protection against the coronavirus changed as scientists obtained better understanding of the modes of transmission and developed vaccines.
Lessons from immunity teach us that the best defensive strategy may change over time. Likewise, we need to adapt—to changing personal circumstances, to changing attackers and attacks, to a changing political or economic climate to an evolving virus—to deploy effective and appropriately tailored defensive strategies.
Sometimes we best help ourselves by helping others.
Second, we need to recognize that defense is costly and continuous. With hundreds of millions of immune cells constantly circulating through our bodies and residing in every organ, it is clear that the evolutionary response to constant threat is constant vigilance.
We seem to recognize in national defense that we cannot afford to let our guard down, even when no enemy is currently attacking. We have been less effective at vigilance in defending against disease. As the time since the last frightening or catastrophic disease increases, investments in public health infrastructure, monitoring, and science decline. Viruses are ever present (and far more abundant) than enemy combatants.
Third, when the systems we are trying to protect are all identical, the attacker only needs to devise an attack against one system, and it immediately has a method for attacking all, as in the case of agricultural monocultures where an entire crop can be wiped out by a single species of pest. The immune system uses many tricks that vary from one individual to the next across a population, providing population-level robustness through heterogeneity.
Fourth, we have to recognize that much defense is a “weakest link” problem. One’s front security door with the keyed-entry lock, shatterproof glass, and alarm is no good if the back window is wide open. This may mean that protecting the things or people we care about most means investing in others. If we are trying to protect the nation against invasive species, a dollar spent in a foreign port enhancing their phytosanitary measures may be more cost effective than one spent on home soil. When it comes to viruses that don’t respect national boundaries, sending vaccines to poorer countries may make far more sense—even if we are being wholly selfish and concerned only with national welfare—than administering a fourth booster at home. Sometimes we best help ourselves by helping others.
There is still much more we’re learning about the fine-tuned machinery of the ancient immune system. The more we learn about the diverse and layered defenses that have emerged in immune systems after millions of years of innovating, the more we can identify promising paths that can be used to protect other things we hold dear. 
Stephanie Forrest directs Arizona State University’s Biodesign Center for Biocomputation, Security and Society, is a professor of computer science, and is an external professor at the Santa Fe Institute. Her interdisciplinary research focuses on the intersection of biology and computation, including cybersecurity, software engineering, and biological modeling.
Ann Kinzig is an Arizona State University professor in the School of Life Sciences, Biosocial Complexity Initiative, School for the Future of Innovation in Society, and program director of ecology, economics, and ethics of the environment at the university’s Center for Biology and Society.
Stuart Feldman is a computer scientist and chief scientist of Schmidt Futures who leads the Scientific Knowledge programs.
Andrea L. Graham is a professor of ecology and evolutionary biology at Princeton University and an external faculty member at the Santa Fe Institute. Her research focuses on the causes and consequences of immunological heterogeneity among animals, especially mammals infected by parasitic worms or plagued by autoimmune diseases.
Simon Levin is the James S. McDonnell Distinguished University Professor in Ecology and Evolutionary Biology at Princeton University and the director of the Center for BioComplexity in the Princeton Environmental Institute.
Jennifer Rexford is a computer scientist and the Gordon Y.S. Wu Professor and Department Chair in Engineering at Princeton University. Her research includes networking and network visualization.
Edward Schrom is a mathematical immunologist and postdoctoral researcher at the National Institutes of Health’s Laboratory of Immune System Biology.
Lead image: SkyPics Studio / Shutterstock
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