The primary candidates for non-cellular life are viruses. A minority of biologists consider viruses to be living organisms, but most do not. Their primary objection is that no known viruses are capable of autonomous reproduction: they must rely on cells to copy them. However, the recent discovery of giant viruses that possess genes for part of the required translation machinery has raised the prospect that they may have had extinct ancestors that could evolve and replicate independently. Most biologists agree that such an ancestor would be a bona fide non-cellular lifeform, but its existence and characteristics are still uncertain. Engineers sometimes use the term 'artificial life' to refer to software and robots inspired by biological processes, but these do not satisfy any biological definition of life. The nature of viruses was unclear for many years following their discovery as pathogens. They were described as poisons or toxins at first, then as 'infectious proteins', but with advances in microbiology it became clear that they also possessed genetic material, a defined structure, and the ability to spontaneously assemble from their constituent parts. This spurred extensive debate as to whether they should be regarded as fundamentally organic or inorganic — as very small biological organisms or very large biochemical molecules — and since the 1950s many scientists have thought of viruses as existing at the border between chemistry and life; a gray area between living and nonliving. The recent discovery of giant viruses (aka giruses, nucleocytoplasmic large DNA viruses, NCLDVs) has reignited this debate, since they are not only physically larger than previously known viruses, but also possess much more extensive genomes, including genes coding for aminoacyl tRNA synthetases, key proteins involved in translation, which were previously thought to be exclusive to cellular organisms. This raises the prospect that the giant viruses may have had extinct ancestors (or even undiscovered ones) capable of engaging in life processes (such as evolution and replication) independent of cells, and that modern viruses lost those abilities secondarily. The viral lineage including this ancestor would be ancient and may have originated alongside the earliest archaea or before the LUCA. If such a virus is discovered, or its past existence supported by further genetic evidence, most biologists agree that it would constitute a bona fide lifeform, and its descendants (at least the giant viruses, and possibly including all known viruses) could be phylogenetically classified in a fourth domain of life. Discovery of the pandoraviruses, with genomes are even larger than the other giant viruses and exhibiting particularly low homology with the three existing domains, further discredited the traditional view that viruses simply 'pick-pocketed' all of their genes from cellular organisms, and further supported the 'complex ancestors' hypothesis. Ongoing research is being conducted in this area, using techniques such as phylogenetic bracketing on the giant viruses to infer characteristics of their proposed progenitor. Furthermore, Viral replication and self-assembly has implications for the study of the origin of life, as it lends further credence to the hypothesis that life could have started as self-assembling organic molecules. Viroids are the smallest infectious pathogens known to biologists, consisting solely of short strands of circular, single-stranded RNA without protein coats. They are mostly plant pathogens and some are animal pathogens, from which some are of commercial importance. Viroid genomes are extremely small in size, ranging from 246 to 467 nucleobases. In comparison, the genome of the smallest known viruses capable of causing an infection by themselves are around 2,000 nucleobases in size. Viroids are the first known representatives of a new biological realm of sub-viral pathogens. Viroid RNA does not code for any protein. Its replication mechanism hijacks RNA polymerase II, a host cell enzyme normally associated with synthesis of messenger RNA from DNA, which instead catalyzes 'rolling circle' synthesis of new RNA using the viroid's RNA as a template. Some viroids are ribozymes, having catalytic properties which allow self-cleavage and ligation of unit-size genomes from larger replication intermediates.