Bacteriology is the study of bacteria. This subdivision of microbiology involves the identification, classification, and characterization of bacterial species. Bacteria are single-celled microorganisms that lack a nuclear membrane, are metabolically active and divide by binary fission. Medically they are a major cause of disease. Superficially, bacteria appear to be relatively simple forms of life; in fact, they are sophisticated and highly adaptable. Major advances in bacteriology over the last century resulted in the development of many effective vaccines (e.g., pneumococcal polysaccharide vaccine, diphtheria toxoid, and tetanus toxoid) as well as of other vaccines (e.g., cholera, typhoid, and plague vaccines) that are less effective or have side effects. The modern methods of bacteriological technique had their beginnings in 1870–85 with the introduction of the use of stains and by the discovery of the method of separating mixtures of organisms on plates of nutrient media solidified with gelatin or agar. Bacteriological study subsequently developed a number of specializations, among which are agricultural, or soil, bacteriology; clinical diagnostic bacteriology; industrial bacteriology; marine bacteriology; public-health bacteriology; sanitary, or hygienic, bacteriology; and systematic bacteriology, which deals with taxonomy. Bacteria, along with blue-green algae, are prokaryotic cells. That is, in contrast to eukaryotic cells, they have no nucleus; rather the genetic material is restricted to an area of the cytoplasm called the nucleoid. Prokaryotic cells also do not have cytoplasmic compartment such as mitochondria and lysosomes that are found in eukaryotes. However, a structure that is found in prokaryotes but not in eukaryotic animal cells is the cell wall which allows bacteria to resist osmotic stress. These cell walls differ in complexity and bacteria are usually divided into two major groups, the gram-positive and gram-negative organisms, which reflect their cell wall structure.