The human lineage entered a more carnivorous niche 2.6 mya. A range of evidence indicates this increased zoonotic pathogen pressure. This evidence includes increased zoonotic infections modern hunter-gatherers and bushmeat hunters relative to others living in the same environments, exceptionally low stomach pH compared to other primates, human-specific down-regulation in ANTXR2 that would have protected against increased exposure to zoonotic anthrax, exceptional human immune responses to LPS compared to other primates, and other divergent immune genes. These all point to change, and likely intensification, in the disease environment of Homo compared to earlier hominins and other apes. At the same time, the brain, an organ in which inflammatory immune responses are highly constrained, begins to increase, eventually tripling in size.

We propose that the combination of increased zoonotic pathogen pressure and the challenges of defending a large brain and body from pathogens across what would eventually become the longest lifespan of any mammal, selected for intensification of the self-medication strategies already in place in apes and other primates, resulting in a variety of plant-based pathogen defenses. In support, there is evidence of medicinal plant use by hominins in the middle Paleolithic, and all cultures today have sophisticated, plant-based medical systems, incorporate plant components high in secondary compounds (spices) into food, and regularly consume psychoactive substances that are harmful to helminths and other pathogens in the CNS and other tissues. The computational challenges of discovering effective plant-based treatments, and the economic challenges of benefiting from costly-to-acquire medical knowledge that would be more often useful to others than oneself, were selection pressures for increased cognitive abilities and unique exchange relationships in Homo. In the story of human evolution, which has long featured hunters, shamans and healers had an equal role to play.