The first example of an experimental autocatalytic set was created in 1994 in the lab of Günter von Kiedrowski [1]. This system consisted of two short nucleotide sequences that mutually catalyze each other’s formation from even shorter fragments. The catalysis was due to complementary base-pair formation.


A schematic overview of Von Kiedrowski’s experimental autocatalytic set. The two molecule types AA and BB mutually catalyze each other’s production through temporary base-pair formation. From [2].

In 2004, a 9-member autocatalytic set of peptides was created experimentally by Gonen Ashkenasy [4]. In 2012, autocatalytic sets of long nucleotide sequences, with up to 16 members, formed from shorter fragments in the lab of Niles Lehman [5]. A very different, but also autocatalytically self-replicating molecular system that forms from a combinatorial library is actively being studied in the lab of Sijbren Otto[6].


An example of a 3-member autocatalytic set as produced in the Lehman lab. Each of the three covalent RNA molecules (E1, E2, and E3) catalyzes the production of the next one (black arrows). From [5].

These results represent exciting progress on the experimental side. However, most of these systems were carefully designed, starting from already existing polymer fragments. One particularly big challenge currently still remaining is to have autocatalytic sets emerge spontaneously in a laboratory setting from more basic building blocks. Further experimental studies of the currently existing systems, and steps towards a more spontaneous emergence and evolution of autocatalytic sets are part of the current collaboration.

[1] D. Sievers and G. von Kiedrowski. Self-replication of complementary nucleotide-based oligomers. Nature 369: 221–224, 1994.
[2] V. Patzke and G. von Kiedrowski. Self replicating systems. ARKIVOC 2007(5): 293–310, 2007.
[3] T. A. Lincoln and G. F. Joyce. Self-sustained replication of an RNA enzyme. Science 323: 1229–1232, 2009.
[4] G. Ashkenasy, R. Jegasia, M. Yadav and M. R. Ghadiri. Design of a directed molecular network. Proceedings of the National Academy of Sciences 101: 10872–10877, 2004.
[5] N. Vaidya, M. L. Manapat, I. A. Chen, R. Xulvi-Brunet, E. J. Hayden and N. Lehman. Spontaneous network formation among cooperative RNA replicators. Nature 491: 72–77, 2012.
[6] H. Duim and S. Otto. Towards open-ended evolution in self-replicating molecular systems. Beilstein Journal of Organic Chemistry 13: 1189–1203, 2017.