One recurring theme for this book is that people in the past have not been stupid, they were just working with a shallower understanding of how the world works.  Folks noticed that certain diseases seemed to move from a sick person to well people in their vicinity.  With no microscopes or knowledge of a world of microscopic organisms, no one could figure out how diseases could move, or where they came from in the first place.  Some folks did believe that the spread was through invisible animacules that could fly from person to person.

As microscopes revealed that diseases were associated with tiny organisms, the first assumptions about disease was based upon the idea of spontaneous generation - it was known that decomposing material "produced" similar cells, and wasn't sickness a sort of decomposition?  So for some time, it was thought that a sick person somehow generated the microroganisms that naturalists were finding associated with particular diseases.  This made more sense than you would expect, since one early discovery was the association of strep bacteria to complications of childbirth.  We know that healthy people harbor strep, and can carry it from sick person to susceptible person without the carrier being sick, and spores introduced internally to a new mother or to a newborn baby can produce life-threatening conditions, but it made more sense based on what was then known that the patients had made those cells themselves.

Louis Pasteur did much of his early work understanding the chemistry of fermentation processes.  He realized that many organic materials, like the alcohols made in wine and beer formation, were produced only when certain microscopic organisms were present, and the wrong mixture of microorganisms were associated with chemistry of spoilage, including spoilage of milk.  In working to study these organisms, he and others developed ways to kill them - testing required organism-free control groups - and adapted these as sterilization techniques that turned out to have very widespread health applications.  One of these is pasteurization.  Pasteur also realized how conditions affect what types of organisms were present, even that some microbes would only appear under low or no-oxygen (hypoxic or anaerobic) conditions.

Joseph Lister had developed surgery techniques to minimize transfer of infectious organisms through application of carbolic acid, both introduced into wounds and sprayed in the air over surgeries (it worked, but was also fairly toxic to the humans there as well).  He also developed methods to produce pure cultures of microbes by dilutions so extreme that only one cell of the most common organism was left to start a pure population.

Robert Koch applied rules to the identification of disease-causing microorganisms, then all called viruses but now called pathogens, as the Koch Postulates:
     - The pathogens must be present in all diseased individuals.
     - You must be able to culture the pathogens from sick individuals, especially from associated lesions.
     - Cultured pathogens can cause disease themselves (it helps to have a susceptible animal model - Koch produced tuberculosis in guinea pigs).
     - Individuals made sick from cultured pathogens produce theose pathogens when sick.
Koch also developed culturing methods, including growing bacterial colonies on types of gelatin.

Ferdinand Cohn discovered that sterilization techniques might not work on organisms in their spore forms - the spores often have resistance to temperatures or chemicals that would kill active cells.

Antibiotics, chemicals that could be safely administered to humans to kill microorganisms (sometimes specifically bacteria), were developed in the 1930's and 1940's, with new types added mostly through the 1970's.  These generally interfere with some chemistry that microbes use but human cells do not.  Antibiotic resistance will be covered below.

The best way to grasp how diseases work is to realize that hosts are basically ecosystems in which many microorganisms live - right now, there might be more prokaryote cells on and in you than you have cells yourself.  Most of those cells cause no problems - they take nothing of significance, and they change nothing for the worse - and many of those cells, our symbionts, give you important gifts.

Living in a large individual presents many challenges to the residents:
     -  They must be able to access and gain necessary resources for their survival.
     -  They require certain conditions for their own optimal performance.  This connects to what sort of host they are "jumping" from - there needs to be significant similarity for the conditions to be suitable.
     -  They must be able to survive defensive reactions from the host, at least until...
     -  They must be able to move offspring to other hosts.

Disease is generally tied to these issues.  Very often, serious diseases have recently moved from one host type to a new one.  The organisms may have been, likely were, much more benign in the old host, and it is incompatibilities between pathogen and host that can seriously compromise the host's chemistry.  The metabolic products of the pathogen may be toxic, or the pathogen accesses resources in a way that deprives the host.  In some cases, pathogens may be able to change local conditions to suit themselves - pathogens in some body cavities may produce discharges tied to how they change the local mucus.

Defensive reactions may put pathogens under a deadline - in many animals, the generalized early defenses may be evaded, but specific defenses (like antibodies) cannot.  Populations must build up and offspring must be sent off before defenses eliminate the pathogens.  In some cases, pathogens use defenses to spread offspring:  coughing and sneezing is totally useless against many respiratory diseases, but the organisms purposely trigger such responses to move their offspring on.

Generally, diseases become less deadly and debilitating the longer they are associated with a particular host.  Here, coevolution is a major factor - hosts with major compatibility issues are more likely to die, those more compatible will show resistance to the disease and likely pass those resistances on to offspring.  Pathogen variants that are more compatible with hosts keep their hosts healthier, vastly increasing the chances for their offspring to pass to new hosts.  It is rare for a disease organism to benefit from quickly killing its host.  So the organisms are both evolving in their relationship, with changes on one side affecting changes on the other.  Typically, because of much shorter generations, pathogens tend to evolve faster than hosts.    Many resident microbes (microbiome) are probably descended from pathogens that could evade host defenses and eventually could live there with no negative effects on the host.

Prokaryotes can generally be called bacteria, although taxonomically they are not technically bacteria.  It is designation of prokaryotes that is used for the Domain level on the taxonomic list, what was used as Kingdoms in the introductory Six-Kingdom system.  The main distinctions are based upon significantly different chemistry and gene expression processes, beyond the scope of this chapter;  an oversimplification would label the Archaea as generally extremophiles, capable of living in some pretty inhospitable environments.  There are Archaea in very hot ecosystems, such as hot springs and hydrothermal vents;  some in environments with excessive amounts of typically toxic materials;  some whose processes produce lots of methane.  The Monera or Eubacteria (see how it can be confusing?) are found in less extreme environments and are therefore more common where humans are.

Prokaryotes also need to be contrasted to eukaryotes, found in the other Domain / Kingdoms.  Eukaryote cells have internal chambers, including a nucleus, where processes can be isolated from the rest of the cell;  prokaryotes very rarely have chambers of internal membranes.  Multicelled systems are always made of eukaryote cells.  There are single-celled eukaryotes, but prokaryotes are only single-celled.  It is rare that prokaryotes even associate in colonies.

Reproduction in prokaryotes is asexual, using a single loop-shaped chromosome;  eukaryotes have pairs of 2-ended chromosomes that allow sexual reproduction, although not all eukaryotes reproduce that way.  Prokaryotes, like eukaryotes, use the genes they need when they need them, so members of "pure" cultures may not all behave identically, and epigenetic modifications can make "genetically identical" subpopulations different for generations. Prokaryotes generally make and share plasmids, like small limited chromosomes, carrying just a few genes, typically genes that are used a lot.  Alleles that are particularly useful may be put in plasmids and passed to other cells somewhat indiscriminately;  since prokaryotes often depend on neighbours of different species, they might pass alleles to help keep them alive.  This can be dangerous:  alleles for antibiotic resistance can be passed from benign residents to incoming pathogens.  This is why use of antibiotics should be done very carefully.

Prokaryote cells tend to be much smaller that eukaryote cells, and come in a fairly limited number of shapes:  round coccus, bar-shaped bacillus, curved vibrio, wavy spirillum, curly spirochetes, and a few that combine shapes.