Cross posted from my blog
I have spent some time reviewing the literature on an approach to dealing with human pathogens known as “virulence management”. Here, I hope to provide a jumping-off point to the field for others. I have included a list of relevant papers at the end.
Our journey starts with the first of three papers by Stephen M. Hedrick on what he calls “Disease Ecology”. Of all of the papers I link here, his paper The Acquired Immune System : A Vantage from Beneath is the one I recommend the most.
The final line of the abstract is perhaps the most striking:
By selecting for ever-more-devious parasites, the acquired immune system is the cause of it’s own necessity.
What does he mean by this? Hedrick reminds us that acquired immunity is a relatively recent invention. While all animals are beset by parasites, invertebrates lack an adaptive immune system. How can they survive without an immune system that can adapt to new pathogens? Hedrick’s main point is: they don’t have to.
Because pathogens rely on their host to survive, they face a strong evolutionary pressure to avoid killing their host. In animals without an adaptive immune system, the host and pathogen find a stable equilibrium. As Hedrick points out, invertebrates are doing fine despite having parasites.
In animals with an acquired immune system (read: humans), the immune system is constantly adapting to new pathogens, forcing these pathogens to adapt as well. Pathogens mutate quickly and have short generation times in order to adapt to changes in the host immune environment. Hosts recombine genes using sexual reproduction along with an amazingly sophisticated immune system in order to combat this.
Hedrick argues that the massive number and diversity of pathogens combined with their short generation times makes the task of the adaptive immune system futile, we don’t have a way to permanently out-adapt such a versatile threat.
But if the invertebrates are doing fine without acquired immunity, how did we get locked into this endless struggle with pathogens?
Evolution doesn’t care about whether a trait is useful to a population, it only cares about you out-competing your neighbor. In this sense, adaptive immunity can be highly beneficial. Unfortunately, this fitness advantage meant that adaptive immunity spread to the entire population, locking us in a wasteful struggle against an enemy we cannot defeat.
So pathogens are a fact of life, but what determines how sick we get?
Pathogens and hosts coevolve. Hosts evolve to mitigate the damage done by the pathogen, while pathogens evolve to avoid the hosts defenses and steal resources. But pathogens must avoid taking too many resources from the host; if they do, the host could die, and bring the pathogen down with them. The degree to which a pathogen damages it’s host is called “virulence”, and the tradeoff between virulence and host health is the focus of optimal virulence theory.
The exact nature of the tradeoff between stealing resources and host health depends strongly on how the pathogen is transmitted. If the pathogen is transmitted by direct contact between hosts, it can’t make the host too sick, otherwise the host will never come into close contact with others. For example, HIV has relatively little effect on its host for years before culminating in AIDS. Surface and air-transmitted pathogens face similar tradeoffs, as their hosts must come in proximity to other hosts in order to transmit. However, some pathogens bear few of the costs of host virulence. Diseases such as malaria do not rely on hosts contacting other hosts, but rather, rely on mosquitos to transfer the disease. In fact, incapacitating hosts may make it easier to transmit malaria, as it is easier for mosquitos to bite an immobile host. This helps explain why malaria is such a devastating disease.
Hedrick closes by suggesting that technology and the acquired immune system may not be up to the task of stopping pathogens. Instead, our best chance to reduce the impact of infectious disease may come from sanitation, vector control, and education.
Despite technological advances, it seems that pathogens will remain a part of our lives for the near future. However, the evolutionary lens offers new opportunities for managing infections.
Paul W. Ewald has suggested that we might be able to make pathogens evolve lower levels of virulence. This is the guiding principle behind “virulence management”. If we can change the evolutionary context pathogens live in, we can modify them to be less harmful.
There are several ways to do this. Sanitation and eradication of insect vectors can force a pathogen to use transmission modes which require close contact between hosts and thus less severe disease. Stronger behavioral responses to illness can also help. For example, if individuals who felt ill avoided contact with other people, pathogens would face strong incentives to leave their hosts unharmed.
It important to consider the impacts of vaccination in this context. Vaccines are extremely valuable for their ability to make infections less deadly. However, it seems that vaccines also encourage short infections and rapid mutation, which matches our understanding of the cold, flu, and coronavirus.
Virulence management remains a relatively unexplored field and presents a promising route to the management of human disease. By changing our goal from eradication to domestication, we may discover a way to live peacefully with a problem almost as old as life itself.
To assist research in this area, I close with a list of relevant publications:
Stephen M. Hedrick’s series on disease ecology:
Understanding Immunity through the Lens of Disease Ecology
The Acquired Immune System: A Vantage from Beneath
Paul W Ewald has a short talk about domesticating diseases and a textbook on the evolution of disease.
Some papers studying the evolution of human pathogens:
The evolution of transmission mode
Within-Host Population Dynamics and the Evolution and Maintenance of Microparasite Virulence
The evolution and expression of virulence
Worms and malaria: noisy nuisances and silent benefits
Some examination of the implications of vaccination for pathogen evolution:
The evolutionary consequences of vaccination
Imperfect vaccines and the evolution of pathogens causing acute infections in vertebrates
General reviews of virulence management:
Beyond killing: Can we find new ways to manage infection?
Darwinian interventions: taming pathogens through evolutionary ecology
Challenging the trade-off model for the evolution of virulence: is virulence management feasible?