Stanley Miller's forgotten experiments, analyzed

June 25, 2014
This is a close-up of the spark that simulates the energy provided by lightning on the early Earth. Credit: Georgia Tech

Stanley Miller, the chemist whose landmark experiment 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. The first-ever analysis of some of Miller's old samples has revealed another way that important molecules could have formed on early Earth.

The study discovered a path from simple to complex compounds amid Earth's prebiotic soup. More than 4 billion years ago, could have been attached together, forming peptides. These peptides ultimately may have led to the proteins and enzymes necessary for life's biochemistry, as we know it.

In the new study, scientists analyzed samples from an experiment Miller performed in 1958. To the reaction flask, Miller added a chemical that at the time wasn't widely thought to have been available on early Earth. The reaction had successfully formed peptides, the new study found. The new study also successfully replicated the experiment and explained why the reaction works.

"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 the Scripps Institution of Oceanography at the UC San Diego. Bada was a former student and colleague of Miller's.

The study was supported by the Center for Chemical Evolution at the Georgia Institute of Technology, 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 work was primarily a collaboration between UC San Diego and the Georgia Institute of Technology in Atlanta. Eric Parker, the study's lead author, was an undergraduate student in Bada's laboratory and is now a graduate student at Georgia Tech.

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."

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Graduate student and study first author Eric Parker talks about the famous spark discharge experiment and the latest findings from a first-ever analysis of Miller's samples from 1958. Credit: Georgia Tech

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 an electric discharge experiment conducted with cyanamide in 1958 when Miller was at the Department of Biochemistry at the College of Physicians and Surgeons, Columbia University.

An electric discharge experiment simulates early Earth conditions using relatively simple starting materials. The reaction 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.

Vials contain samples of prebiotic materials created by Stanley Miller in 1958, labeled by Miller himself. Miller added a potential prebiotic condensation agent, cyanamide, during the course of the experiment. Cyanamide has been suggested to induce polymerization of amino acid into simple peptides which is an important set in chemical evolution and possibly the origin of life. For unknown reasons, Miller had never analyzed the samples. In a paper published in 2014, researchers at Georgia Tech and Scripps Institution of Oceanography at UC San Diego analyzed the samples and established the potential importance of reagents - substances that cause chemical reactions such as cyanamide -- in the origin of life on Earth. Credit: Scripps Institution of Oceanography, UC San Diego.

"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."

In the experiment from 1958, Stanley Miller had the idea to use the organic compound cyanamide in the reaction. Scientists had previously thought that the reaction with cyanamide would work only in acidic conditions, which likely wasn't widely available on early Earth. The new study showed that reactive intermediates produced during the synthesis of amino acids enhanced peptide formation under the basic conditions associated with the spark discharge experiment.

"What we've done is shown 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. In 1958, Miller was at Columbia University in New York City. Researchers at both Columbia 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 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 Miller's .

"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 part of an 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 Stanley published in Science in 1953. In 2011, the researchers analyzed a 1958 experiment that used hydrogen sulfide as a gas in the experiment. The reactions produced a more diverse array of amino acids that had been synthesized in Miller's famous 1953 study. Eric Parker was the lead author on the 2011 study.

"It's been an amazing opportunity to work with a piece of scientific history," Parker said.

Explore further: 'Lost' samples from famous origin of life researcher could send search for first life in new direction

More information: Eric T. Parker, et al., "A Plausible Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth." Angewandte Chemie, June 2014.

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1.5 / 5 (10) Jun 25, 2014
"ultimately may have" is what I would call "close, but no cigar" or in other words, the experiments got us no closer to the answer we wanted to hear :( As a follow up to the March 2011 story, are we *any* closer to Frankenstein's dream?
Jun 25, 2014
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Steve 200mph Cruiz
5 / 5 (14) Jun 25, 2014
How is this not science verkle?
They had the hypothesis that if you combine specific molecules with and electric discharge it would create amino acids.
Then they tested it, and got a positive response, this is a perfectly valid idea, and it's better than the alternatives you proposed (crickets chirping)

So tell me how did amino acids form proteins possibly during the late Hadean eon and definitely had been in swing by the Archean Eon?

Evolution is just the contextual consequence of the observable fact that DNA does not replace perfectly all the time. To disprove evolution you have to observe a constant perfect creation of DNA, which doesn't exist.
5 / 5 (13) Jun 25, 2014
To disprove evolution you have to observe a constant perfect creation of DNA, which doesn't exist.

That's a really interesting point actually. Verkle's creationist argument is that mutations are always negative.

So verkle if that's the case, how come we haven't "devolved"? What's the mechanism that prevents degeneration? Because let me tell you, with the advent of cheap large scale genome mapping, your "hand of god" Texas-schoolbook-ID-fundie hypothesis is fast becoming statistically testable!
1.7 / 5 (9) Jun 26, 2014
I don't see how the theory of evolution has any relevance here. It postulates that the diversity of life on earth came about by changes in living organisms over time. How life got started in the first place is beyond the scope of the theory of evolution. Miller tried to prove that some of the building blocks of living organisms could have formed spontaneously. He succeeded, but amino acids are not alive. As Teledyn pointed out, it gets us no closer to proving that life could have formed spontaneously from a soup of organic compounds. It just proved that certain organic compounds necessary for living organisms could have formed spontaneously. That's no more helpful than proving that oxygen, carbon dioxide, and water--also necessary for living organisms--could have formed spontaneously.
5 / 5 (6) Jun 26, 2014
I don't see how the theory of evolution has any relevance here. It postulates that the diversity of life on earth came about by changes in living organisms over time. How life got started in the first place is beyond the scope of the theory of evolution.

Actually, "survival of the fittest" is quite appropriate when considering random chemical reactions, most of which result in nothing, but a select few of which begin to replicate. Life is a subset of natural chemical reactions, but the "living" ones happen to repeat themselves. It's a variation on the theme of other repeating patterns, including crystallization. Nothing magical about it.
Steve 200mph Cruiz
4.8 / 5 (5) Jun 26, 2014

You're wrong in the basic postulation of your argument.
Evolution is really just the first law of thermodynamics:
(wikipedia) First law of thermodynamics: Heat is a form of energy. Because energy is conserved, the internal energy of a system changes as heat flows in or out of it. Equivalently, perpetual motion machines of the first kind are impossible.

All chemistry is driven by the conservation of energy, as such all the environmental niches driven by the conservation of energy. The organisms that are most likely to survive are the ones that make the most of every single organisms specific environment. The threshold conservation of energy in ecological systems is what we call a niche. Deer in America, kangaroos in Australia.
You really are only chemistry, otherwise pharmaceuticals wouldn't work. But by mass, life is by far the rarest thing in the universe, black holes are mundane to our general experience of just being alive, this is special, no one is trying to disprove that
1 / 5 (4) Jun 26, 2014
jimbo92107 and Steve 200mph Cruiz, the theory of evolution is as I stated. It describes how the diversity of life on earth came to be, not how life got started in the first place. There may be similarities in the non-biological world to aspects of evolution, but they are described by other theories. Evolution is a theory about already existing life (biology), not chemistry or thermodynamics.

There is a dramatic difference in complexity and behavior between cellular organisms that self-replicate and adapt and inanimate chemical reactions that repeat due to the laws of physics. Any perceptive person can recognize that even a single cell organism is "alive" and chemicals are not.
5 / 5 (1) Jun 26, 2014
I believe it is incorrect to separate the fundamental tenets of the theory of evolution (the great synthesis model) from more basic biochemistry / chemistry / quantum dynamics - these all fall within a polar spectrum ranging from absolute determinism to pure indeterministic randomicity - study morphogenetic fields such as discovered by Gurwitsch et al - these show evolutionary dynamics operating at basic levels of organised complexity.
not rated yet Jun 26, 2014
A few years ago I saw the results of an experiment performed by subjecting amino acids to brief but intense pressure, such as 10,000 to 15,000 atmospheres. The amino acids were among those found in carbonaceous chondrites, with the pressure presumably mimicking those created during an impact event. The results were long-chain molecules, peptides among others, but I can't recall the scientist's name or find her research again. Does anyone here remember seeing this study? TIA
Steve 200mph Cruiz
5 / 5 (5) Jun 26, 2014
"Evolution is a theory about already existing life (biology), not chemistry or thermodynamics."

Aksdad, ALL sciences are connected. Everything exists in context of everything else around it.
A fire does not light without oxygen, a sauropod does not evolve without trees.
That's what natural selection is.
How about viruses? They are just protein shells that are completely inanimate when left to their own devices, and "live" until they are degraded chemically. But they change over time in the context of their environment and they do evolve.
Maybe viruses were really just some of the first carnivores to evolve out of the goop of proteins and have stayed ecologically viable all these eons.
Not only that, maybe some protein structures found safe havens from viruses in lipid bi-layers, oh man, suddenly you have something resembling a cell.
Course that's just a half baked idea, but think critically about what this data means in context, by definition, that's what makes some consequential.
5 / 5 (5) Jun 26, 2014
Don't mind the anti-scientist creationist crackpots trolling! Let them rave futilely while science succeeds as the articles they comment under shows. They have zero credibility.


Re evolution and the emergence of life:

Analogously to how the theory of general relativity is not dependent on how non-inertial mass appears to predict the dynamics of stars, the theory of evolution is not dependent on how the first population appeared to predict the dynamics of populations.

But same as the mechanisms of general relativity predict some mass appearance (inertial mass), the mechanisms of evolution predict some features of emergence, such as selection on chemical as opposed to biological populations. The difference is in the overall process so in the overall theory. Before there were hereditary material (hereditary replicators), chemical population evolution in geophysical systems can probably be better described as a form of lamarckian evolution as opposed to darwinian evolution.
3.7 / 5 (3) Jun 26, 2014

E.g. we still have "small, survivable steps" coupled to forms of selection. But the acquired traits are kept as much by accumulation.

I buy that evolution is an example of the 1st law of thermodynamics (LOT), since it establishes niches and those obey tropic (energy flow) rules. Life and its emergence on the other hand is an example of the 2nd LOT, since geophysics and hence systems derived from it (us) are non-equilibrium (NE) systems. Without entropy and metabolic engines there would be little order, just the freezing out of complexity by symmetry breaking that chemical evolution starts with. (E.g. Standard Model of particles et cetera.)

Now metabolism and later heredity organizes spontaneously as epiphenomena of NE thermodynamics.
4 / 5 (4) Jun 26, 2014

The process of emergence of life is natural, it has nothing to do with reanimating dead bodies which was done on frogs in the 18th century, hence Shelley's book.

As the article notes, these experiments are informative on life emergence, so they observably brought us closer to understanding it and its details.

The emergence of life is arguably solved in the biological sense. Astrobiology started to pare down instead of amassing theories in the 00's. As soon as you see shared traits in almost life protocells and modern cells you have a testable phylogeny (that is "the biological sense"). And if you have pared it down to a smaller subset it is well tested, the main thing is to get the topology correct. (See e.g. "29+ evidences for Macroevolution".)

4 / 5 (4) Jun 26, 2014

And people proposed such shared traits 2013 (Lane & Martin, Russell et al). The theory, submarine alkaline hydrothermal emergence, has so many shared traits that it knocks out the remaining main contender "RNA world". This year the essential non-equilibrium core metabolism could be tied to an equilibrium sugar metabolism of Hadean oceans. (Keller et al.)

That is AFAIK the first time sugar metabolism is derived from chemical evolution. (It's just heat, Fe2+ and absence of oxygen, for shouting out loud!) That opens up for the nucleotide based cofactors and eventually RNA, which early forms (mRNA, rRNA, tRNA) are still catalytic under the same conditions. (RNA is heat adapted, so is the UCA enzymes.)

Miller synthesis could be a coevolution of an RNA takeover that is necessary before we see the RNA UCA cell we know from more detailed phylogenies.
1 / 5 (1) Jun 28, 2014
Evolution is just the contextual consequence of the observable fact that DNA does not replace perfectly all the time. To disprove evolution you have to observe a constant perfect creation of DNA, which doesn't exist.

Fallacy alert:
Assumption that a creator wouldn't want DNA to have the potential to change is conjecture.

In fact, most information systems we think about have dynamic data components, particularly computer memory and even machines for making other machines, such as injection molds.

It's a very long way from some random amino acids in a man-made glass flask to a fully functional prokaryote, or even a much simpler, fully functional virus for that matter.

You need to explain where a reuseable biocatylitic structure, such as the Ribosome, came from.

How do you randomly throw some DNA and/or RNA and a few peptides in an ocean and come out with a Proto-cell with Ribosomes, lipids, ~1000 ordered genes, and a fully functional Replicaton-Translation-Transcription cycl
not rated yet Jun 29, 2014
Evolution is just the contextual consequence of the observable fact that DNA does not replace perfectly all the time. To disprove evolution you have to observe a constant perfect creation of DNA, which doesn't exist.

Fallacy alert:
Assumption that a creator wouldn't want DNA to have the potential to change is conjecture.

Fallacy alert:
Even if your supposed creator did want DNA to change, the method of change would still be evolution and it still wouldn't be disproven.

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