While reading a review yesterday, I recalled a conversation I had with a student nearly forty years ago. He did not appear interested in the subject of my lectures – bacterial genetics and physiology – so I was curious to know the reasons why. To my query he replied with deadpan humor: "Roberto, E. coli is nice, but it is not the T-cell receptor." His reply was an eye opener. In my fascination with bacterial molecular biology, I had failed to give broad context to my lectures. But his reply also revealed that, in general, the fascination with molecular detail that characterized the biological sciences of a half a century ago (and to some degree continues to this day) tended to shut us out from integrative views of the living world. Yet all it takes is a few minutes in quiet contemplation of the world around us – perhaps during a walk in a forest – to realize that life is all about interactions. How organisms adapt in the presence of others is fundamental to the evolutionary history of life on Earth. In that view, terms such as "pathogen" tend to lose their strict meaning. It is best to think in terms of when and where is an interaction pathogenic.
The authors of the review I mentioned take on the subject matter by presenting what is known about how some microbes that can cause severe disease in humans often fail to produce disease in their natural host, what they refer to as pathogen tolerance. One of their key points is that there's a pernicious problem in the way we perceive pathogens: "Unfortunately, our understanding of infection and disease has been overtly biased by how we perceive pathogens that infect us. Since pathogens by definition reduce host fitness (e.g., through increased mortality or reduced fecundity), host-pathogen interactions have been traditionally viewed as purely antagonistic. Consequently, studies on pathogen defense have primarily focused on mechanisms that hosts typically use to resist infections by activating immune responses. This bias has led us to ignore mechanisms that facilitate the host's ability to coexist with pathogens and withstand their negative fitness effects by reducing pathogen- or immune-mediated damage." A second key point is that host-microbe co-evolution yields tolerance, and this increases the pathogen's numbers and carriage period, creating a genetically diverse pathogen pool where variants able to infect new hosts may arise. The current experience with SARS-CoV-2 makes this all too apparent.
This review proved extremely thought provoking. Mind you, it is not an easy read so be prepared to take in a huge amount of information. For me, however, the main take-home message is that we should stop thinking as specialists in separate "disciplines" such as immunology or ecology. Rather, we need to think as generalists, able to integrate all of the life sciences.