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Bioethics Forum Essay

Pathogens and Humans

In a 1988 essay on pandemics, Nobel laureate Joshua Lederberg wrote, “We have no guarantee that the natural evolutionary competition of viruses with the human species will always find ourselves the winner.” When Lederberg made these comments, HIV had already taken more than 100,000 lives. The advent of antiretroviral drugs in the 1990s and their ability to control the rate of replication inside the body have allowed us to stay one step ahead of the virus causing this disease. But one day one or more pathogens may emerge that no vaccine can control. Although it may not be likely, the competition between viruses or other pathogens and humans could lead to our demise.

From the 5 million deaths it has caused thus far, the SARS-CoV-2 pandemic is a palpable example of the pathogenic threat to our existence. This threat is associated with an increase in viruses that can jump from nonhuman to human animals. The incidence of zoonotic diseases has been accelerated by humans encroaching on natural habitats, deforestation, and an increase in interspecies interaction. Vaccines may weaken the virulence and limit the spread of some viruses. But the emergence of new variants, such as Omicron, the new coronavirus variant, may give them an evolutionary advantage.

We may be able to predict the evolution of viruses and prepare vaccines against them with techniques such as deep mutational scanning, which uses DNA sequencing to measure a large number of protein variants in viruses. These pre-emptive interventions could program people’s immune systems to prevent viruses from causing disease and death. But success is not assured. Epigenetic factors shaped by a natural environment significantly different from our own could affect the evolution of these variants and the efficacy of vaccines against them.      

The idea that we can “enhance” the immune system to protect us from pathogenic threats fails to appreciate the complexity of immunity. A “supercharged” immune response to an infection could release an uncontrolled cascade of inflammatory cytokines, causing multiple organ failure. It could also disrupt the immune system’s ability to distinguish self from nonself and result in autoimmune disease.  

While mortality from SARS-CoV-2 has been highest among the elderly, mortality from the 1918 influenza was highest among people with an average age of 28. One hypothesis for why younger people were so adversely affected by this pandemic is that they were likely exposed to the H3N8 influenza strain when they were born, around 1890. This exposure may have primed their immune systems to respond to the antigen from this virus rather than to the antigen from the H1N1 virus of 1918. There was no vaccine for the 1918 H1N1 influenza.  But the mortality from it suggests that cellular responses to viral variants depend on the history of immune interaction with viruses and on which antigenic memory is most salient in the adaptive arm. The precise mechanism behind the different immune responses in 1918 is not entirely understood. But it suggests that some immune mechanisms designed to protect the organism from some pathogens can make it susceptible to others at different times.                      

We cannot assume that viruses will always evolve in ways that can be controlled. It would be hubristic to make this assumption. Vaccines may not always generate the necessary acquired immunity because they may not always keep up with random genetic mutations in antigens. Mutations can cause viruses to weaken. But they might also allow them to evade all immune defenses. While this obviously would be bad for humans, causing them to suffer and shortening their lives, in natural biological terms it would be neither good nor bad but one possible amoral outcome of interaction between pathogens and human organisms. Claims to the contrary would reflect an anthropocentric view of nature.

Humans can change behaviors to decrease the risk of life-threatening zoonotic diseases, for example, by protecting natural habitats through limits on deforestation. The combination of these behaviors and vaccines may allow us to keep these diseases endemic and prevent them from becoming epidemic or pandemic. But while these measures can reduce this risk, they cannot eliminate it. The thought that humans could lose in a competition with one of more pathogens is distressing. It could exacerbate the harm from the death, long-term disability, and restrictions of individual freedom that already have resulted from SARS-CoV-2.  Yet, as Lederberg noted, it is one possible outcome of sharing the planet with microbes and one that we cannot ignore.  

Walter Glannon, PhD, is a professor emeritus of philosophy at the University of Calgary and a Hastings Center fellow.

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