The origin of intracellular and intercellular pathogens

I propose that the very earliest cells could not have contained intracellular parasites in the sense of independent, self-benefiting agents that were detrimental to their hosts. Before there were effective ways to extract energy by methanogenesis and photosynthesis, the world ecosystem, I have argued, was very sparse and essentially monophyletic (Koch, 1994). During much or all of this time, nontransmissible agents, comparable to plasmids, would have been selected against as long as they could not synchronize their growth with that of their single-celled host. Even when such an adaptation was initiated, it must have been one that was likely crude and imperfect, and frequently failed. The transmission of genetic material via subcellular vectors would have depended on the later development of special mechanisms for the introduction of nucleic acids into living cells. Only after living forms became abundant could an efficient and effective transmissible intracellular pathogen prosper, because by then a transmissible agent could be destructive to its host and move successfully to a new host. The implication is that much of the earliest evolution of either the host's cellular functions or the parasite's techniques and strategies proceeded without gene transfer. Support for these ideas is presented, starting from hypotheses concerning the nature of the first life forms and leading to a scenario for the development of transmissible intracellular pathogens.