The three-domain system is a biological classification introduced by Carl Woese, Otto Kandler, and Mark Wheelis in 1990 that divides cellular life forms into three domains, namely Archaea, Bacteria, and Eukaryota. The key difference from earlier classifications such as the two-empire system and the five-kingdom classification is the splitting of Archaea from bacteria as completely different organisms. It has been challenged by the two-domain system that divides organisms into Bacteria and Archaea only, as Eukaryotes are considered as one group of Archaea. Woese argued, on the basis of differences in 16S rRNA genes, that bacteria, archaea, and eukaryotes each arose separately from an ancestor with poorly developed genetic machinery, often called a progenote. To reflect these primary lines of descent, he treated each as a domain, divided into several different kingdoms. Originally his split of the prokaryotes was into Eubacteria (now Bacteria) and Archaebacteria (now Archaea). Woese initially used the term "kingdom" to refer to the three primary phylogenic groupings, and this nomenclature was widely used until the term "domain" was adopted in 1990. Acceptance of the validity of Woese's phylogenetically valid classification was a slow process. Prominent biologists including Salvador Luria and Ernst Mayr objected to his division of the prokaryotes. Not all criticism of him was restricted to the scientific level. A decade of labor-intensive oligonucleotide cataloging left him with a reputation as "a crank", and Woese would go on to be dubbed "Microbiology's Scarred Revolutionary" by a news article printed in the journal Science in 1997. The growing amount of supporting data led the scientific community to accept the Archaea by the mid-1980s. Today, very few scientists still accept the concept of a unified Prokarya. The three-domain system adds a level of classification (the domains) "above" the kingdoms present in the previously used five- or six-kingdom systems.

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