Pathogens Don't Exist
It takes a partnership to have a disease, say two microbiologists who argue for ditching the word “pathogen.”
Pathogens – disease germs – seem so real, it looks really cranky to claim they don’t exist. Isn’t the Ebola virus a terrible pathogen that doctors are fighting in Africa? But listen to Casadevall and Pirofsky in Nature today:
The term pathogen started to be used in the late 1880s to mean a microbe that can cause disease. Ever since, scientists have been searching for properties in bacteria, fungi, viruses and parasites that account for their ability to make us ill. Some seminal discoveries have resulted — such as the roles of various bacterial and fungal toxins in disease. Indeed, our oldest and most reliable vaccines, such as those for diphtheria and tetanus, work by prompting the body to produce antibodies that neutralize bacterial toxins.
Yet a microbe cannot cause disease without a host. What actually kills people with diphtheria, for example, is the strong inflammatory response that the diphtheria toxin triggers, including a thick grey coating on the throat that can obstruct breathing. Likewise, it is the massive activation of white blood cells triggered by certain strains of Staphylococcus and Streptococcus bacteria that can lead to toxic-shock syndrome.
Disease is one of several possible outcomes of an interaction between a host and a microbe. It sounds obvious spelled out in this way. But the issue here is more than just semantics: the use of the term pathogen sustains an unhelpful focus among researchers and clinicians on microbes that could be hindering the discovery of treatments.
Imagine a staph germ just sitting there in the environment. It’s not hurting anyone. It might even have a beneficial function. It’s your fault. It’s your darn body that gets carried away in an overreaction, they seem to be saying. That is certainly a novel way to think about disease germs!
Could we find treatments easier by changing our focus from the evil germ to the uncooperative interactions of innocent cells with our bodies? “Context is everything,” Casadevall and Pirofsky argue, providing several examples of how the same microbe can cause different effects in different people. There are clear-cut cases of knocking out the “virulence factors” in tetanus and diphtheria, but success against pneumonia-causing agents has been difficult.
Work on vaccines has provided further indications of there being flaws in the idea that discrete factors, akin to toxins, enable all microbes to cause disease. What is more, many of the ongoing attempts to develop new vaccines by identifying and targeting virulence factors have so far proved fruitless. Despite decades of searching, no classical virulence factor suitable for vaccine development has been identified for the tuberculosis bacillus or malaria parasite.
What do they suggest? They acknowledge that getting “pathogen” out of the dictionary is not going to happen, but we should recognize the metaphor’s limitations. It’s a “reductionist” approach, they say, to treat the host as a constant and the microbe as a variable. Instead, researchers need to focus more on the host-microbe interaction:
New tools are needed to measure the spectrum of inflammatory, biochemical and other forms of damage resulting from the interaction between hosts and microbes. The discovery and development of these tools must be driven by new sessions at conferences, special issues of journals and dedicated funding streams. We think that such a shift in approach would uncover all sorts of possibilities for preventing infectious diseases.
Related Health Issues
Toxin sharing: A related article in Science Daily talks about “virulence agents” like “microbe toxin genes,” in Lyme disease bacteria, but then shares the surprising news that “Microbe toxin genes have jumped to ticks, mites and other animals.” There seems to be some kind of arms-trade agreement going on. We’re all familiar with the picture of the evil germ injecting its poison into the host, but—
Now, in a surprising twist, Mougous and colleagues [U of Washington] have found that many animals have taken a page from the bacterial playbook. They steal these toxins to fight unwanted microbes growing in or on them. The researchers describe their findings in a report to be published online Nov. 24 in the journal Nature.
This finding opens the possibility that the enemy of my enemy is my friend, in the internal battle for homeostasis. By horizontal gene transfer, animals can hack the software bacteria use to fight their own enemies. But then, is warfare a proper metaphor at all?
How the toxins function in organisms other than ticks remains to be explored. The researchers now are looking at the possibility that other bacterial toxins have been repurposed by animals for antibacterial defense.
Toxic fruit: PhysOrg has a story about fruit flies that have adapted to the toxic fruit of a certain tree. All other species of fruit flies are killed by it, but this one species is not repulsed by the odor. “The flies are strongly attracted by the fruits of the morinda tree: they feed on its fruits, and females prefer to lay their eggs on these.” What’s poison to one is food to another.
Snake venom: Snakebite: now there’s a really scary situation for humans. Once inside the body, those toxins can wreak havoc on nerves, muscles and tissues, and even cause death. But take a look at the “new model of snake venom evolution proposed” in Science Daily. Maybe the snake wasn’t nefariously plotting to cause us pain.
Researchers [at U of Texas] have found genetic evidence that highly toxic venom proteins were evolutionarily ‘born’ from non-toxic genes, which have other ordinary jobs around the body, such as regulation of cellular functions or digestion of food.
The researchers are identifying the functions of these toxins “before they evolved into toxins.” Obviously they are not toxic to the snake, who manufactures and stores them. Are snakes just repurposing their original household tools for later needs, like hunting and defense?
Castoe said that with an uptick in genetic analysis capabilities, scientists are finding more evidence for a long-held theory. That theory says highly toxic venom proteins were evolutionarily “born” from non-toxic genes, which have other ordinary jobs around the body, such as regulation of cellular functions or digestion of food.
“These results demonstrate that genes or transcripts which were previously interpreted as ‘toxin genes’ are instead most likely housekeeping genes, involved in the more mundane maintenance of normal metabolism of many tissues,” said Stephen Mackessy, a co-author on the study and biology professor at the University of Northern Colorado. “Our results also suggest that instead of a single ancient origin, venom and venom-delivery systems most likely evolved independently in several distinct lineages of reptiles.”
This thinking meshes a little with the ideas from Casadevall and Pirofsky: it’s misleading to consider snake venom a “pathogen” of sorts. We must focus on the interaction of the substance within the host body. Those genes would tend to become more expressed at higher levels—up to a point:
Based on their data, the new paper presents a model with three steps for venom evolution. First, these potentially venomous genes end up in the oral gland by default, because they are expressed in low but consistent ways throughout the body. Then, because of natural selection on this expression in the oral gland being beneficial, tissues in the mouth begin expressing those genes in higher levels than in other parts of the body. Finally, as the venom evolves to become more toxic, the expression of those genes in other organs is decreased to limit potentially harmful effects of secreting such toxins in other body tissues.
This is not Darwinian natural selection; it’s just adjustment of existing genetic information (how much it is expressed, and in what tissues). The snakes don’t want to shoot themselves in the foot! (Note: snakes do not have feet.) Snakes are not evil sinners, but some evolutionary models are:
The team calls its new model the Stepwise Intermediate Nearly Neutral Evolutionary Recruitment, or SINNER, model. They say differing venom levels in snakes and other animals could be traced to the variability of where different species, or different genes within a species, are along the continuum between the beginning and end of the SINNER model….
“What is a venom and what species are venomous will take a lot more evidence to convince people now,” Castoe said. “It provides a brand new perspective on what we should think of when we look at those oral glands.”
What all these stories have in common is the repurposing of existing genetic information as interactions between organisms are explored in various environments.
We offer these news items to creation ecologists who would like to consider possible avenues for the origin of “natural evil.” The Curse as described in Genesis 3 may not have involved creation of harmful agents de novo. Instead, it may have involved minor adjustments to existing structures, or relaxation of controls on the maintenance of structures, or relaxation of controls on interactions between organisms. Instead of a controlled, harmonious ecosystem, it became a more chaotic ecology, with organisms getting by as best they could, within certain constraints (God’s continuing care for His creation). Anyway, these are new and interesting ways to think about the issues.