Stanley Miller, the late UC San Diego chemist, is one of the architects of the famous “primordial soup” experiments of the 1950s that simulated the conditions on early Earth that may have led to the origin of life on the planet.
But Miller’s accomplishments have continued even after his death in 2007. His carefully preserved lab samples and meticulous notes have left a trail of bread crumbs for new generations of researchers still seeking to explain how life originated on Earth. Now, a new analysis of samples that Miller created in 1958, but for unknown reasons never analyzed himself reveals that a certain chemical he added as a potential ingredient of life aided the formation of peptides, key components of living matter.
“It was clear that the results from this old experiment weren’t some sort of artifact. They were real,” said Jeffrey Bada, distinguished professor of marine chemistry at Scripps Institution of Oceanography at UC San Diego. Bada was a former student and colleague of Miller’s.
Miller, a chemist whose landmark experiment with Harold Urey published in 1953 showed how some of the molecules of life could have formed on a young Earth, left behind boxes of experimental samples that he never analyzed. In this study, Bada and colleagues at Georgia Institute of Technology discovered a path from simple to complex compounds amid Earth’s prebiotic soup after analyzing the samples and then replicating the analysis with newly created samples.
In both cases, the Scripps-Georgia Tech research team used the compound cyanamide, a chemical Miller had added to the samples. Only in the 1960s, some years after Miller had created these samples, did other scientists begin to suggest that the compound was widely available on early Earth.
The reaction created by Bada and the other researchers successfully formed simple peptides, the new study found. The new study also successfully replicated the experiment and explained why the reaction works.
The study was supported by the Center for Chemical Evolution at Georgia Tech, which is jointly supported by the National Science Foundation and the NASA Astrobiology Program. The study was published online June 25 in the journal Angewandte Chemie International Edition. The study was led by Eric Parker, a graduate student at Georgia Tech who was an undergraduate student in Bada’s laboratory.
Jeffrey Bada was Stanley Miller’s second graduate student. The two were close and collaborated throughout Miller’s career. After Miller suffered a severe stroke in 1999, Bada inherited boxes of experimental samples from Miller’s lab. While sorting through the boxes, Bada saw “electric discharge sample” in Miller’s handwriting on the outside of one box.
“I opened it up and inside were all these other little boxes,” Bada said. “I started looking at them, and realized they were from all his original experiments; the ones he did in 1953 that he wrote the famous paper in Science on, plus a whole assortment of others related to that. It’s something that should rightfully end up in the Smithsonian.”
The boxes of unanalyzed samples had been preserved and carefully marked, down to the page number where the experiment was described in Miller’s laboratory notebooks. The researchers verified that the contents of the box of samples were from a set of electric discharge experiments conducted in 1958 when Miller was at the Department of Biochemistry at the College of Physicians and Surgeons, Columbia University.
Miller’s original electric discharge experiments and their modern counterparts simulate early Earth conditions using relatively simple starting materials. A reaction in the lab is ignited by a spark, simulating lightning, which was likely very common on the early Earth.
The 1958 reaction samples were analyzed by Parker and his current mentor, Facundo M. Fernández, a professor in the School of Chemistry and Biochemistry at Georgia Tech. They conducted liquid chromatography- and mass spectrometry-based analyses and found that the reaction samples from 1958 contained peptides. Scientists from NASA’s Johnson Space Center and Goddard Space Flight Center were also involved in the analysis.
The research team then set out to replicate the experiment. Parker designed a way to do the experiment using modern equipment and confirmed that the reaction created peptides.
“What we found were some of the same products of polymerization that we found in the original samples,” Parker said. “This corroborated the data that we collected from analyzing the original samples.”
Prior to 1958, scientists had previously found that a reaction involving cyanamide would occur only in mildly acidic conditions, which likely were not widespread on early Earth. The new study showed that reactive compounds (termed intermediates) formed during the series of reactions that eventually resulted in the synthesis of amino acids enhanced peptide formation under the basic conditions associated with the spark discharge experiment.
“What we’ve shown is that you don’t need acid conditions; you just need to have the intermediates involved in amino acid synthesis there, which is very reasonable,” Bada said.
Why Miller added cyanamide to the reaction will probably never be known. Bada can only speculate. Researchers at both Columbia, where Miller worked, and the close-by Rockefeller Institute were at the center of studies on how to analyze and make peptides and proteins in the lab, which had been demonstrated for the first time in 1953 (the same year that Miller published his famous origin of life paper). Perhaps while he was having coffee with colleagues, someone suggested that cyanamide – a chemical used in the production of pharmaceuticals – might have been available on the early Earth and might help make peptides if added to his reaction.
“Everybody who would have been there and could verify this is gone, so we’re just left to scratch our heads and say ‘how’d he get this idea before anyone else,’” Bada said.
The latest study is the latest of three papers describing the ongoing analysis of Stanley Miller’s old experiments. In 2008, the research team found samples from 1953 that showed a much more efficient synthesis than Miller published in Science in 1953. In 2011, the researchers analyzed a different 1958 experiment that used hydrogen sulfide as a gas in the electric discharge experiment. The reactions triggered in that experiment produced a more diverse array of amino acids than had been synthesized in Miller’s famous 1953 study. Parker was also the lead author of the 2011 study.
“It’s been an amazing opportunity to work with a piece of scientific history,” he said.