Spiegelman‘s Monster

In 1965 Sol Spiegelman managed to make short strands of RNA in a test tube and let them replicate autonomously. He mixed RNA from a simple bacteriophage Q? with Q?’s RNA replication enzyme, some free nucleotides, and some salts.

The RNA worked just like it would in a living organism, and it even went through something like an artificial evolution: taking a little of the resulting RNA and adding it to a second replicating system – repeating this step again and again – led to a shortening of the RNA while it became more efficient at replicating itself. After 74 generations, what started out as an RNA strand with 4500 nu-cleotide bases ended up as a dwarf genome with only 220 bases. This raw replicator with no gene expression abilities could replicate very fast. It was soon to be called Spiegelman’s Monster – even the researchers used the term in their publications.

It was the first time that a piece of nucleic acid made in the test tube worked as well as the stuff made in nature. Spiegelman had achieved the first synthesis of a biologically competent, infective viral nucleic acid. The press was excited and wrote about “the dream experiment of modern biology”, but came up with “Frankenstein” analogies at the same time. Spiegelman didn’t like the  comparison, he didn’t think he had tinkered around with artificial life: “When you create a living object the presumption is that the object didn’t exist before. This I did not do. Working with simple chemical compounds, I take a primer of a living object and I generate many living objects from it.”

Spiegelman, S., Haruna, I., Holland, I.B., Beaudreau, G. & Mills, D. (1965). “The Synthesis of a Self-prop- agating and Infectious Nucleic Acid with a Purified Enzyme”. PDF of the original paper here.

By Roland Fischer