In the late 1850s, the revolutionary work of Louis Pasteur further contributed to the body of evidence for germ theory as he determined the role of bacteria in causing diseases. Robert Koch identified the bacterium that causes tuberculosis, Mycobacterium tuberculosis (Koch, 1882). He also introduced four criteria used to demonstrate that the relationship between a microorganism and a disease is causal; these are known as Koch’s Postulates (Koch, 1884). The first virus isolated was the Tobacco Mosaic virus in 1892 by the Russian botanist Dmitri Ivanoski, but was not recognized as a “virus” until several years later after further investigations by Martinus Beijerinck in 1898 (Scolthof et al., 1999). Critically, Beijerinck’s studies proved that microorganisms include the non-cellular forms we now recognize as viruses.
The word pathogen was first used in the 19th century, following the wide acceptance of the germ theory of disease (Casadevall and Pirofski, 2014). The definition of a pathogen, and an understanding of its true nature, remained unresolved for some time.  The modern definition of a pathogen most often used is a microorganism that causes, or can cause disease (Pirofski and Casadevall, 2012). This definition, however, is situated within a medical framework, rather than an evolutionary one. This evokes a fundamental question of the nature of pathogens: are there inherent differences between pathogenic and non-pathogenic species? Many of the first described pathogenic microbes were encapsulated or toxigenic bacteria, bolstering the idea that pathogens were distinct lineages of microorganisms.
In the mid-20th century, the argument that pathogens were unique lineages of organisms began to disintegrate, and pathogenic and non-pathogenic microorganisms presented overlapping characteristics. Research showed that microbes could exist in pathogenic and non-pathogenic states by, for example, attenuation in the laboratory. Medical developments such as widely used broad-spectrum antimicrobial agents, immunosuppressive therapies, and newer types of surgery altered host–microbe interactions. These altered dynamics led to an important insight: microbe species that were first considered non-pathogenic could become, in fact, pathogenic. One example is Candida albicans, a yeast living in the gastrointestinal tract and the genitourinary tract (Singh et al., 2014). In healthy hosts, C. albicans is the commensal yeast that is harmless to the host and benefits from a stable habitat of the host body. Under specific circumstances, such as when the host develops immune disorders (such as AIDS) or following a course of antibiotic treatment, the yeast population can proliferate, becoming overabundant and causing candidiasis. Pathogenicity is therefore not only a microbial trait but the outcome of host–microbe interaction and how the immune system reacts to this interaction.  As a result of this, some researchers have argued that the term “pathogen” should be ditched altogether in the medical field (Casadevall and Pirofski, 2014).  

Reshaping our understanding

Parasites and pathogens are frequently understood or approached from a non-neutral or partial perspective. This taints our understanding of them as inherently negative which can erode scientific efficacy. Because of our natural inclination to think of ourselves as healthy because we are parasite-free, we project that same idea onto other organisms. A parasite going extinct will often elicit the response “Good riddance!”, even among biologists (Windsor, 1995). This instinct has real and material effects: as parasites are thought of as always harmful, many animals in conservation programs are rid of parasites, which can make them go extinct. For example, the critically endangered Californian condor (Gymnogyps californianus) was kept in zoos as part of a breeding program, where the birds were treated with a pesticide to get rid of their lice. This treatment killed the last remaining host-specific Californian condor lice (Colpocephalum californici), a form of the paradoxically named conservation-induced extinction (Rózsa and Vas, 2015). While the decision to eliminate the lice for the benefit of the condor has broad appeal, it is important to admit that this is an aesthetic and hierarchical valuation rather than a scientific one. In conservation, parasites tend to be valued less and receive less funding than their host, even though parasites are the most threatened mode of life (Lafferty, 2012). Only recently have parasite conservation programs been put into practice, and it is still considered to be a major oversight in conservation biology (Carlson et al., 2020).
This leads to a different issue faced by parasites: co-extinction. A single species going extinct will usually have cascading effects. The species’ parasites (and commensals and mutualists) risk going extinct with their host, as they are dependent on it to survive. This is especially true of obligate parasites and parasites, which are very host-specific (Dunn et al., 2009). Documentation on co-extinction has historically been lacking, due to incomplete taxonomy and a lack of experiments (Colwell et al., 2012). Models suggest as many as 30% of parasitic worms may go extinct by 2070 (Carlson et al., 2017). Parasites are often not even considered in biodiversity surveys, both due to the lack of knowledge and because of the fear of introducing host species to new parasites. More recently there have been calls to include parasites in conservation strategies (Jørgensen, 2015). Parasites are in themselves a native part of biodiversity and can constitute up to 75% of an ecosystem’s resource-consumer webs (Dougherty et al., 2015). Having rich parasite biodiversity could be considered a good measure of ecological health (Colwell et al., 2012).
Adding to the challenge of understanding parasitology, parasites can be difficult to classify and are frequently confused with mutualists or commensals. This is made even more complicated by the multi-modal nature of some species interactions. For example, Caribbean cleaning gobies (Elacatinus evelynae) cleaning longfin damselfish (Stegastes diencaeus) switch their interactions between mutualistic, neutral, or parasitic depending on the number of ectoparasites present for cleaning on the damselfish (Cheney and Côté, 2005). Similarly, a recent study on arbuscular mycorrhizal fungal communities of Joshua trees (Yucca brevifolia) showed a spectrum of fungal interaction modes—from mutualism to parasitism—correlated with both elevational gradient and host plant developmental age (Harrower and Gilbert, 2021). We also take note of the example of brachiobdellid annelids that graze on the exoskeletons of freshwater crayfish (Cambaroides similis). This grazing has been reported as anywhere from minority parasitic to mutualistic with experiments demonstrating that the nature of this interaction is impacted by environmental conditions (Lee et al., 2009; Skeleton et al., 2013).
Scientists are routinely confronted with the pliable, shifting, and sometimes contradictory webs of ecology. Likewise, the field of microbiology has substantially altered perceptions of individualism in nature by revealing the staggering diversity of microbes living within and amongst multicellular organisms. Although it is quite practical to recognize individual organisms or distinct taxa in science, it is also useful to understand organisms as embedded in biological interdependencies. This phenomenon is captured by the holobiont concept (Margulis, 1991) or hologenome concept (Jefferson, 1994) which emphasizes that the biological characteristics of an organism are most legible when understood as a collection of multispecies interactions over evolutionary time. Microbiologists continue to illuminate the blurred limits of an individual species (e.g., how would the human body function without our microbiota?); this framework also is useful for recasting our understanding of parasitism and pathology.
Similarly, it is most scientifically accurate to emphasize that the impact a pathogen has on its host is the outcome of the evolutionary interaction between both. For example, if the host has a good chance of transmitting the pathogen to other hosts, then a phenotype that includes high reproduction and high infectivity (and usually also high virulence) could be beneficial for the pathogen. If, however, the host does not come into contact with many other hosts, then a more benign character of the pathogen could be an evolutionarily beneficial phenotype for the pathogen. In other words, a pathogen is as much a reflection of its own DNA and phenotype as it is the DNA and phenotype of its host. Hegner et al. (1938) argue that “the principles that govern the structure, life cycles, habitats and activities of free-living and parasitic animals are really the same.” Indeed, it is increasingly apparent that these definitions are contextual, and depend greatly on the perceived value of the organisms in question.

Parasitic and pathogenic fungi

Sometimes species are assumed to be parasites without evidence, and sometimes language originating from parasitological or pathogenic biology is incorrectly applied to other forms of symbiosis. For example, throughout foundational literature on endophytic and mycorrhizal fungi, terminology such as “infect” is widely used to describe the interaction (Newman, 1988Arnold et al., 2003). This term is used even when the fungi in question are demonstrably beneficial to the host plant, which belies a fundamental perception of fungi as being pathogenic or at least dubious (Kaishian and Djoulakian, 2020). Because fungi are also typically excluded from conservation efforts and biodiversity monitoring programs (Fiesler and Drake, 2016; Haelewaters et al., 2024), fungal parasites are doubly at risk of being overlooked. Laboulbeniales, for example, are obligatorily associated with various arthropods (Weir and Hammond, 1997Haelewaters et al., 2021), but the nature of their characterization has been debated. Are they parasites or rather commensals? The answer may be that Laboulbeniales occupy an overlapping range of both on the spectrum of symbiosis. Based on micro-computed tomography imaging, Reboleira et al. (2021) concluded that some species of Laboulbeniales are “ectobionts,” whereas others are “ectoparasites.” However, Konrad et al. (2015) also found some evidence for these fungi to provide benefits to their host—in their protection against infection by entomopathogenic fungi. While the limits of the continuum that Laboulbeniales occupy on the symbiosis spectrum are unclear, we know that they are not pathogens, despite having been labeled as such (e.g., Espadaler et al., 2011).