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Prebiotic Soup--Revisiting the Miller Experiment [biogenesis]
Science Magazine ^ | May 2003 | Jeffrey L. Bada and Antonio Lazcano

Posted on 11/02/2003 10:30:46 AM PST by PatrickHenry

"Isn't life wonderful?" sang Alma Cogan and Les Howard in their almost forgotten 1953 hit. That same year, Stanley L. Miller raised the hopes of understanding the origin of life when on 15 May, Science published his paper on the synthesis of amino acids under conditions that simulated primitive Earth's atmosphere (1). Miller had applied an electric discharge to a mixture of CH4, NH3, H2O, and H2--believed at the time to be the atmospheric composition of early Earth. Surprisingly, the products were not a random mixture of organic molecules, but rather a relatively small number of biochemically significant compounds such as amino acids, hydroxy acids, and urea. With the publication of these dramatic results, the modern era in the study of the origin of life began.

Since the late 19th century, the belief in a natural origin of life had become widespread. It was generally accepted that life's defining properties could be understood through physico-chemical characterization of "protoplasm," a term used to describe the viscous translucent colloid found in all living cells (2). Expressions like "primordial protoplasmic globules" were used not only by scientists but also in fiction, from Gilbert and Sullivan's Pooh-Bah in The Mikado (1885) to Thomas Mann's somber imaginary character Adrian Leverkühn in Doktor Faustus (1947). But few dared to be explicit, even in novels. Questioned about the origin of life, a chemist in Dorothy L. Sayers' novel The Documents in the Case (1930) states that "it appears possible that there was an evolution from inorganic or organic through the colloids. We can't say much more, and we haven't--so far--succeeded in producing it in the laboratory."

Some were willing to fill in the details. At the turn of the 20th century, many scientists favored the idea of primordial beings endowed with a plant-like (autotrophic) metabolism that would allow them to use CO2 as their source of cellular carbon. However, some scientists--including A. I. Oparin, J. B. S. Haldane, C. B. Lipman, and R. B. Harvey--had different ideas (3). The most successful and best-known proposal was that by Oparin, who, from a Darwinian analysis, proposed a series of events from the synthesis and accumulation of organic compounds to primordial life forms whose maintenance and reproduction depended on external sources of reduced carbon.

The assumption of an abiotic origin of organic compounds rested on firm grounds. In 1828, F. Wöhler had reported the first chemical synthesis of a simple organic molecule (urea) from inorganic starting materials (silver cyanate and ammonium chloride).

After a large body of research on the synthesis of simple organic compounds accumulated in the 19th century (see figure above), W. Löb achieved the chemical syntheses of simple amino acids such as glycine by exposing wet formamide to a silent electrical discharge and to ultraviolet light (4).

These efforts to produce simple organic compounds from simple reagents heralded the dawn of prebiotic organic chemistry. However, there is no indication that the scientists who carried out these studies were interested in how life began on Earth, or in the synthesis of organic compounds under possible prebiotic conditions. This is not surprising, because the abiotic synthesis of organic compounds was not considered to be a necessary prerequisite for the emergence of life.

From the 1950s, chemists were drawn toward the origin of life. Driven by his interest in evolutionary biology, Melvin Calvin tried to simulate the synthesis of organic compounds under primitive Earth conditions with high-energy radiation sources. He and his group had limited success: the irradiation of CO2 solutions with the Crocker Laboratory's 60-inch cyclotron led only to formic acid, albeit in fairly high yields (5). Miller's publication 2 years later showed how compounds of biochemical importance could be produced in high yields from a mixture of reduced gases.

The origin of Miller's experiment can be traced to 1950, when Nobel laureate Harold C. Urey, who had studied the origin of the solar system and the chemical events associated with this process, began to consider the emergence of life in the context of his proposal of a highly reducing terrestrial atmosphere. Urey presented his ideas in a lecture at the University of Chicago in 1951, followed by the publication of a paper on Earth's primitive atmosphere in the Proceedings of the National Academy of Sciences(6).

Almost a year and a half after Urey's lecture, Miller, a graduate student in the Chemistry Department who had been in the audience, approached Urey about the possibility of doing a prebiotic synthesis experiment using a reducing gas mixture. After overcoming Urey's initial resistance, they designed three apparatuses meant to simulate the ocean-atmosphere system on primitive Earth (3). The first experiment used water vapor produced by heating to simulate evaporation from the oceans; as it mixed with methane, ammonia, and hydrogen, it mimicked a water vapor-saturated primitive atmosphere, which was then subjected to an electric discharge (see the figure below). The second experiment used a higher pressure, which generated a hot water mist similar to that of a water vapor-rich volcanic eruption into the atmosphere, whereas the third used a so-called silent discharge instead of a spark.

Miller began the experiments in the fall of 1952. By comparison with contemporary analytical tools, the paper chromatography method available at the time was crude. Still, after only 2 days of sparking the gaseous mixture, Miller detected glycine in the flask containing water. When he repeated the experiment, this time sparking the mixture for a week, the inside of the sparking flask soon became coated with an oily material and the water turned a yellow-brown color. Chromatographic analysis of the water flask yielded an intense glycine spot; several other amino acids were also detected. Experiments with the second apparatus produced a similar distribution and quantities of amino acids and other organic compounds, whereas the third apparatus with silent discharge showed lower overall yields and much fewer amino acids (primarily sarcosine and glycine).

After Miller showed the impressive results to Urey, they decided to submit them to Science. Urey declined Miller's offer to coauthor the report because otherwise Miller would receive little or no credit. Knowing that a graduate student could have a difficult time getting a paper like this published, Urey contacted the Science editorial office to explain the importance of the work and ask that the paper be published as soon as possible. Urey kept mentioning the results in his lectures, drawing considerable attention from the news media.

The manuscript was sent to Science in early February of 1953. Several weeks went by with no news. Growing impatient, Urey wrote to Howard Meyerhoff, chairman of AAAS's Editorial Board, on 27 February to complain about the lack of progress (7). Then, on 8 March 1953, the New York Times reported in a short article entitled, "Looking Back Two Billion Years" that W. M. MacNevin and his associates at Ohio State University had performed several experiments simulating the primitive Earth--including a discharge experiment with methane wherein "resinous solids too complex for analysis" were produced. The next day, Miller sent Urey a copy of the clipping with a note saying "I am not sure what should be done now, since their work is, in essence, my thesis. As of today, I have not received the proof from Science, and in the letter that was sent to you, Meyerhoff said that he had sent my note for review."

Infuriated by this news, Urey had Miller withdraw the paper and submit it to the Journal of the American Chemical Society. Ironically, at the same time (11 March), Meyerhoff, evidently frustrated by Urey's actions, wrote to Miller that he wanted to publish the manuscript as a lead article and that he wanted Miller--not Urey--to make the final decision about the manuscript. Miller immediately accepted Meyerhoff's offer, the paper was withdrawn from the Journal of the American Chemical Society and returned to Science, and was published on 15 May 1953.

On 15 December 1952, well before the Miller paper was sent to Science, K. Wilde and co-workers had submitted a paper on the attempted electric arc synthesis of organic compounds using CO2 and water to the same journal. They reported that no interesting reduction products, such as formaldehyde, were synthesized above the part-per-million level. This result supported the surmise of Miller and Urey that reducing conditions were needed for effective organic syntheses to take place. Surprisingly, when the paper by Wilde et al. was published in Science on 10 July 1953, it did not mention Miller's paper, although the authors did note that their results had "implications with respect to the origin of living matter on earth."

Miller's paper was published only a few weeks after Watson and Crick reported their DNA double-helix model in Nature. The link between the two nascent fields began to develop a few years later, when Juan Oró demonstrated the remarkable ease by which adenine, one of the nucleobases in DNA and RNA, could be produced through the oligomerization of hydrogen cyanide (8). It would eventually culminate in the independent suggestions of an "RNA world" by Carl Woese, Leslie Orgel, and Francis Crick in the late 1960s and by Walter Gilbert in 1986.

The impact of the Miller paper was not limited to academic circles. The results captured the imagination of the public, who were intrigued by the use of electric discharges to form the prebiotic soup. Fascination with the effects of electricity and spark discharges on biological systems started with the work of L. Galvani in 1780 with frog legs and the discovery of "animal electricity." And an everlasting impression was left in the public's imagination by Mary W. Shelley's Frankenstein (1818), in which Eramus Darwin gained a place for his advocacy of therapies based on electric discharges.

Although in 1953, few envisioned the possibility of Frankenstein monsters crawling out of Miller's laboratory vessels, the public's imagination was captivated by the outcome of the experiment. By the time that the results were corroborated by an independent group 3 years later (9), the metaphor of the "prebiotic soup" had found its way into comic strips, cartoons, movies, and novels, and continues to do so. In Harry Mulisch's novel The Procedure (1998), one of the central characters encounters disaster while paving his way to the glittering halls of Stockholm for achieving the artificial synthesis of life from a primitive soup.

But is the "prebiotic soup" theory a reasonable explanation for the emergence of life? Contemporary geoscientists tend to doubt that the primitive atmosphere had the highly reducing composition used by Miller in 1953. Many have suggested that the organic compounds needed for the origin of life may have originated from extraterrestrial sources such as meteorites. However, there is evidence that amino acids and other biochemical monomers found in meteorites were synthesized in parent bodies by reactions similar to those in the Miller experiment. Localized reducing environments may have existed on primitive Earth, especially near volcanic plumes, where electric discharges (10) may have driven prebiotic synthesis.

In the early 1950s, several groups were attempting organic synthesis under primitive conditions. But it was the Miller experiment, placed in the Darwinian perspective provided by Oparin's ideas and deeply rooted in the 19th-century tradition of synthetic organic chemistry, that almost overnight transformed the study of the origin of life into a respectable field of inquiry.

[Illustrations and footnotes in the original.]


TOPICS: Culture/Society; Miscellaneous; Philosophy
KEYWORDS: abiogenesis; biogenesis; crevolist; earlyearth; evolution; millerexperiment; originoflife
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To: BiffWondercat
"I just find it facinating to have such a biosphere in such adverse conditions. I would think that the protiens organized before DNA/RNA started getting into the business. "

I think that biosphere is fascinating too. And I'm all in favor of exploring it and understanding the creation in all it's glory.

41 posted on 11/02/2003 6:42:35 PM PST by DannyTN (Note left on my door by a pack of neighborhood dogs.)
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To: DannyTN
And even when you've got nothing, their's always imagination

Yes, well, but we don't have "nothing" do we? We have a gobsmack of evidence, from paleo-meteorology, from paleontological excavation, chemical experiments and DNA mutational distance backtracing.

42 posted on 11/02/2003 6:43:04 PM PST by donh (1)
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To: donh
"Yes, well, but we don't have "nothing" do we? "

I think you have a gobsmack of imagination.

43 posted on 11/02/2003 6:47:29 PM PST by DannyTN (Note left on my door by a pack of neighborhood dogs.)
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To: Ogmios
Who needs Extraterrestrials,

Life that evolved on a moon of Jupiter's would be extra-terrestrial. You mean extra-solar, I think.

If it pans out, this has been touted as the biggest news for several centuries, but I suspect it will be a flash in the newspan. Extraterrestials that are smarter, more aquisitive and more aggressive than us might be big news.

44 posted on 11/02/2003 6:49:17 PM PST by donh (1)
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To: DannyTN
I think you have a gobsmack of imagination.

I just report what scientists is up to--no significant imagination required.

45 posted on 11/02/2003 6:50:41 PM PST by donh (1)
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To: BiffWondercat
I would think that the protiens organized before DNA/RNA

That's on the table, and, in fact, a self-reproducing protein, of a sort, has been built (or discovered, depending on your viewpoint). However, I'd not bet my money on this one. My money is riding on phospholipid chains organized by enduring adiabatic chemical cycles. Such as the citric acid cycle. "Organized" is really kind of a misleading word to use in this context.

Think stomachs, not brains.

46 posted on 11/02/2003 6:57:42 PM PST by donh (1)
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To: PatrickHenry
Callisto is supposed to be covered with carbon-nitrogen compounds. A little heat might make something interesting happen.
47 posted on 11/02/2003 7:05:22 PM PST by <1/1,000,000th%
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To: <1/1,000,000th%
With liquid water, carbon, and some trace elements, plus time, there are those who think that life is virtually inevitable. When we finally get around to exploring such places, we may find that life is everywhere.
48 posted on 11/02/2003 7:13:07 PM PST by PatrickHenry
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To: Ogmios
Evolution uses existence as proof with no explanation of existence ... it happens (( globdidit )) ---

you 're comfortable with that ... globdidit --- gobble - gobble - turkey !

49 posted on 11/02/2003 7:18:04 PM PST by f.Christian (evolution vs intelligent design ... science3000 ... designeduniverse.com --- * architecture * !)
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To: PatrickHenry
It certainly seems that way on this planet.
50 posted on 11/02/2003 7:19:01 PM PST by <1/1,000,000th%
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To: LiteKeeper
I believe evolution is definitely a satanic conspiracy --- war with God - truth !

Look how good christians are demonized - banned ... all through society - media --- intelligentsia - cabal !


Main Entry: in·tel·li·gent·sia
Pronunciation: in-"te-l&-'jen(t)-sE-&, -'gen(t)-
Function: noun
Etymology: Russian intelligentsiya, from Latin intelligentia intelligence
Date: 1907
: intellectuals who form an artistic, social, or political vanguard or elite

Main Entry: 1ca·bal
Pronunciation: k&-'bäl, -'bal
Function: noun
Etymology: French cabale cabala, intrigue, cabal, from Medieval Latin cabbala cabala, from Late Hebrew qabbAlAh, literally, received (lore)
Date: 1614
: the artifices and intrigues of a group of persons secretly united to bring about an overturn or usurpation especially in public affairs; also : a group engaged in such artifices and intrigues
synonym see PLOT



51 posted on 11/02/2003 7:35:16 PM PST by f.Christian (evolution vs intelligent design ... science3000 ... designeduniverse.com --- * architecture * !)
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To: donh
I'm afraid you are mistaken, my friend.

Life "evolving" on planet Earth encounters unsurmountable problems, some of which being achirality of all organic molecules without reason, inability to find a hydrophobic environment to link peptide chains (IE not just disparite amino acids and not abiotic addition polymers), lack of stable environment to allow any magical protocell to exist for a measurable amount of time, etc.

So, to escape these high improbabilies, origins researchers contend that life came from a meteor--which incidentally passes the buck to another, more "hospitable" planet. Certain meteors containing achiral (L) amino acids (that might be achrial due to intersteller radiation, but that is a hypothesis) in groups is their best evidence..though it also has great problems (aside from its merely passing of the buck)....
52 posted on 11/02/2003 8:00:40 PM PST by Loc123
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To: jennyp
I tend to believe that mainstream scientific theists are unafraid of scientific discoveries--as it almost always points to a Creator.

This is especially true in the following fields: physics, origin of life, and origin of consciousness.

The improbabilies that the universe was 1) spontaneously generated and 2) beset with the unique and improbable laws of physics (as opposed to trillions of other possibilies outlined in singularity physics) post to the existence of a Creator.

The nearly complete faith foundation of abiogenesis is another--sure there are some theories, but they all seem to have unsurmountable challenges ahead.

I don't know much about these smokestacks, other than they much be both hydrophobic AND phyllic at different times to allow for peptide bonding (a major oversight of many). Also these smokestacks can only be within a certain temp range if certain chemical reactions deemed necessary for even the most simple lifeform (save the immigrated lifeforms near sulfur vents) to function.

The RNA world hypothesis is nearly discredited as being way to advanced for the times. Self-catalyzing RNA outside of a cell is impossibly improbable. And if somehow self-catalyzing RNA got into a "cell," complete with protein channels and a phospholipied layer (also dubious), then it would need a ribosomal structure to synthesize proteins.

And don't even get me started on the mother-of-all-improbabilities--that consciousness could have evolved in the brain over a few million years!
53 posted on 11/02/2003 8:12:33 PM PST by Loc123
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To: Loc123
And don't even get me started on the mother-of-all-improbabilities--that consciousness could have evolved in the brain over a few million years!

For your reading pleasure William Calvin a researcher into consciousness. His theory (leaving out a lot of details) is that it is a result of a large brain that is able to sequence the firing of neurons. This is, in turn, is an adaption to throwing as a means of hunting.

I personally think he's onto something. No other animal can throw accurately.

54 posted on 11/02/2003 8:31:00 PM PST by Virginia-American
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To: Virginia-American
Thanks for the link--I will surely read it later.

I hope he can address HOW a mutation could have been propagated against impossible odds, or how merely increased complexity can lead to inherent, unique/discrete abilities.
55 posted on 11/02/2003 9:34:57 PM PST by Loc123
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To: Virginia-American
I read the most relevant part of his research, found here: http://www.williamcalvin.com/1990s/1998SciAmer.htm

As I suspected, he had absolutely no mechanism by which intelligence, let alone consciousness, may have evolved in the past million or more years.

You must understand, I am not necessarily debating whether intelligence is a survival benefit or detriment; I am debating whether the probability of consciousness evolving in the brain given 1-2 million years is at all probable. Given the complexities and improbabilities of neural evolution, not to mention the unique lifespans and social habits of humans (among dozens of other high improbabilities), it seems prohibitively impossible for human intelligence and consciousness to have evolved without significant intervention.
56 posted on 11/02/2003 9:43:07 PM PST by Loc123
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To: Diddley
Read later.
57 posted on 11/02/2003 10:11:44 PM PST by Diddley (Liberal logic: I support the troops [read police], but I don’t support the war [read fighting crime])
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To: PatrickHenry
Ah, those heady, already waning, days when people believed that organic compounds in nature were derived through biological processes and were surprised, though pleased, to see something of abiogenic origin (even such as ethanol in space) appear in experiments by people such as Wöhler, Miller, et al.

Of course, the unique thing about a living system is not that it synthesizes organic molecules such as amino acids, but that it is able, at standard temperature and pressure (though some extremophiles manage to push the temp/pressure envelope) and non-racemically, to do that which is done abiogenically at extremes inimical to life.

And it has only been in the days since Miller (University of Chicago BUMP) that the staggering complexity at the cellular level has been revealed; a complexity that completely dwarfs anything else in nature. The origin of the control mechanisms and the ability to carry out complex organic synthesis and molecular assembly is far more important than merely the origin of the materials employed in the process. All the problems of going from unicellular life in the pre-Cambrian to the multicellular life of the present (and relatively impoverished) biosphere shrink to insignificance compared to what would be necessary to bridge the gap between a primordial soup and the most minimal functioning cell.
58 posted on 11/02/2003 10:26:10 PM PST by aruanan
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To: Virginia-American
Statistically unlikely Placemarker
59 posted on 11/02/2003 10:49:30 PM PST by Ogmios (Since when is 66 senate votes for judicial confirmations constitutional?)
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To: Virginia-American
I believe we were created to throw so that the Angels could watch baseball in October.
60 posted on 11/02/2003 11:07:29 PM PST by bondserv (Alignment is critical.)
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