Spiegelman Monster is the name given to an RNA chain of only 218 nucleotides that is able to be reproduced by an RNA replication enzyme. It is named after its creator, Sol Spiegelman, of the University of Illinois at Urbana-Champaign.
Spiegelman introduced RNA from a simple bacteriophage Qβ (Qβ) into a solution which contained Qβ's RNA replication enzyme, some free nucleotides, and some salts. In this environment, the RNA started to replicate.  After a while, Spiegelman took some RNA and moved it to another tube with fresh solution. This process was repeated.
Shorter RNA chains were able to replicate faster, so the RNA became shorter and shorter as selection favored speed. After 74 generations, the original strand with 4,500 nucleotide bases ended up as a dwarf genome with only 218 bases. Such a short RNA had been able to replicate very quickly in these unnatural circumstances.
In 1997, Eigen and Oehlenschlager showed that the Spiegelman monster eventually becomes even shorter, containing only 48 or 54 nucleotides, which are simply the binding sites for the reproducing enzyme RNA replicase.
M. Sumper and R. Luce of Eigen's laboratory demonstrated that a mixture containing no RNA at all but only RNA bases and Qβ replicase can, under the right conditions, spontaneously generate self-replicating RNA which evolves into a form similar to Spiegelman's Monster.
- Spiegelman, S., Haruna, I., Holland, I.B., Beaudreau, G. & Mills, D. (1965). "The Synthesis of a Self-propagating and Infectious Nucleic Acid with a Purified Enzyme". Proc. Nat. Acad. Sci. USA 54 (3): 919–927. doi:10.1073/pnas.54.3.919. PMC 219765. PMID 5217468.
- Mills, D. R., R. L. Peterson, Sol Spiegelman (1967). "An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule". Proceedings of the National Academy of Sciences 58 (1): 217. doi:10.1073/pnas.69.10.3038.
- Kacian,D.L., D.R. Mills, F.R. Kramer, S. Spiegelman (1972). "A Replicating RNA Molecule Suitable for a Detailed Analysis of Extracellular Evolution and Replication". Proceedings of the National Academy of Sciences 69 (10): 3038–3042. doi:10.1073/pnas.69.10.3038. PMC 389702. PMID 4507621.
- Oehlenschläger, Frank; Manfred Eigen (1997). "30 Years Later – a New Approach to Sol Spiegelman's and Leslie Orgel's in vitro EVOLUTIONARY STUDIES Dedicated to Leslie Orgel on the occasion of his 70th birthday". Origins of Life and Evolution of Biospheres 27 (5/6): 437. doi:10.1023/A:1006501326129.
- Sumper, M; R. Luce (1975). "Evidence for de novo production of self-replicating and environmentally adapted RNA structures by bacteriophage Qbeta replicase". Proceedings of the National Academy of Sciences 72 (1): 162–166. doi:10.1073/pnas.72.1.162. PMC 432262. PMID 1054493.