Summary (Sep 16, 2003): No single experiment, according to Carl Sagan, has done more to convince scientists that life is 'likely abundant in the cosmos' than the work fifty years ago by then graduate student, Stanley Miller. This week celebrates his milestone publication, and Astrobiology Magazine interviewed him about his work and reflections today.
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Primordial Recipe: Spark and Stir by Astrobiology Magazine staffwriter
Fifty years ago on May 15, 1953, a University of Chicago graduate student, Stanley Miller, published a landmark two-page paper in Science magazine. He considered if amino acids could be made from what was known about the early Earth's atmosphere. Could the building blocks of life be cooked up?
 | "... some warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity etc...", Charles Darwin, on the origins of life in tidal pools
Credit:Smithsonian
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Miller began his paper: "The idea that the organic compounds that serve as the basis of life were formed when the earth had an atmosphere of methane, ammonia, water and hydrogen instead of carbon dioxide, nitrogen, oxygen and water was suggested by Oparin and has been given emphasis by Urey and Bernal. In order to test this hypothesis..."
When Miller first presented his experimental findings to a large seminar, it is reported that at one point, Enrico Fermi politely asked if it was known whether this kind of process could have actually taken place on the primitive Earth. Harold Urey, Stanley's research advisor, immediately replied, saying 'If God did not do it this way, then he missed a good bet'. The seminar ended amid the laughter and, as the attendees filed out, some congratulated Stanley on his results.
Although Miller had submitted his paper in mid-December 1952, one reviewer did not believe the results and delayed its publication until May 15th. Later Carl Sagan would do many experiments varying the chemical percentages, but described the Miller-Urey experiments as "the single most significant step in convincing many scientists that life is likely to be abundant in the cosmos." Early Earth: Flash in a FlaskEven today, only a few definitive things are known about what the Earth might have been like four billion years ago. It is thought that the early sun radiated only 70 percent of its modern power. No free oxygen could be found in Earth's atmosphere. The rocky wasteland lacked life. Absent were viruses, bacteria, plants and animals. Even the temperature itself is uncertain, since three schools of thought today maintain that the Earth could have been alternatively frozen, temperate or steamy.
Charles Darwin imagined life springing from a temperate world, with small ponds or runoff channels. Compared to diluted chemistry in a vast ocean, repeated evaporation and refilling have possible advantages, to find just the right concentrations somewhere so that biochemistry could begin. Glaciers, volcanoes, geysers and cometary debris potentially resupplied this primordial pond with both energy and more complex organic compounds. That is a scenario requiring relatively temperate starting conditions, and more extreme possibilities are also in the mix.
If the early Earth was a cauldron of volcanic activity, then seepage of acidic gases and heating might have circulated vital compounds to the surface. These vents may have been underwater, and precursors to biochemistry like acetic acid may have become reactive in combination with carbon monoxide. Alternatively, if the early Earth lacked any greenhouse of blanketing carbon dioxide, life could still have begun in a ball of ice. When combined with water, even a thin atmosphere of organics (formaldehyde, cyanide and ammonia) can create some building blocks of life (such as the amino acid, glycine). Thawing this 'snowball Earth' could then be triggered by a chance collision with large comets or meteors.
 | | Terrestrial options for early climate. Early earth, snowball, cauldron or temperate?Credit: NASA |
To test whether a primordial pond or ocean could seed the stuff of life, some experiments were needed. Miller laid out an experimental plan. He filled a flask with methane (natural gas), hydrogen and ammonia. Another flask below provided a miniature pond of water, as the model for an early ocean. Discharging flashes of voltage to simulate lightning provided just the necessary spark for new chemistry to begin. When he left the pot to cook overnight, the odds seemed stacked against coming in the next morning to discover the simulated ocean had turned reddish-yellow. But he was surprised: given a simulated ocean, atmosphere and lightning, then a hydrogen-rich mix of methane and ammonia could be transformed to amino soup.
Stanley Miller with his Nobel Laureate supervisor, Harold Urey, demonstrated that 13 of the 21 amino acids necessary for life could be made in a glass flask. Placing water in this atmosphere, sparking a lightning discharge into simple organic molecules like ammonia surprised everyone by producing some of biology's essential building blocks. Indeed the formation of life had begun to take on a distinctly molecular character, as Charles Darwin had foreseen as his classical warm pond of organic soup: ("... some warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity etc..." ).
Miller found that at least 10 percent of the carbon was converted into a small number of organic compounds and about two percent went into amino acids. Hydrogen, cyanide, and aldehydes were also produced. Glycine was the most abundant amino acid produced.
Flash forward fifty years and many high schools chemistry labs routinely repeat Miller's classic result. Lasers are often substituted for high voltage discharges as an energy source, and this dramatically speeds up the signature yellowing of the primordial oceans.
But as the Earth's early chemistry has become better understood, a catch has arisen. Ironically, while complex biochemistry can spring from simpler building blocks, one missing element - the simplest hydrogen - may have been in short supply four billion years ago. Without it, the reactions don't trigger the right organic chemistry. If the Earth more likely was rich in nitrogen and carbon dioxide - rather than hydrogen, methane and ammonia - , then any amount of sparking delivers a mere drop of organic byproducts. The primordial soup is too dilute.
 | | University of Chicago graduate student, Stanley Miller, 1953.Credit: U. Chicago |
Workarounds to get enough concentrated chemistry for self-assembly to arise have reverted to evaporation (such as tidal pools) or a large seeding event from a colliding comet. Both these could quicken the biochemistry enough for life. Interview with Professor Stanley Miller To commemorate the fiftieth anniversary for whom most consider the father of primordial chemistry, Professor Stanley Miller, of the University of California, San Diego, the Astrobiology Magazine had the opportunity to get his perspective today.
Astrobiology Magazine (AB): This is the fiftieth anniversary of your original University of Chicago work. Do you have any retrospective thoughts on what was going through your mind at the moment you starting flipping the electrode switch, and how successfully the experiment would carry forward as a classic at that time?
Professor Stanley Miller (SM): I would say curiosity was probably the primary impetus. Upon observing the results for the first time, my focus was devoted more to the "how and why" than the ramifications.
The actual long-term significance of the experiment has been an evolution in and of itself. I believed the results of the experiment would provide valuable insights into the origin of life, but at that time I hadn't really devoted much thought as to the extent of its influence.
The scientific community's immediate response, as well as that of the public media, was a very big surprise.
AB: What is your current opinion on the need for a primitive reducing atmosphere for pre-biotic life to take hold 3.5 to 3.8 billion years ago?
SM: I have not found an alternative to disprove the need for a primitive reducing atmosphere.
AB: Do you believe that material transported on meteors or comets is insufficient to seed life, if such amino acids were successfully transported intact to the surface of the Earth?
SM: Meteorite and other exogenous contributions become very important only if the earth had a neutral atmosphere. However, if the only sources of organic compounds under such conditions were the very small number of compounds produced with a CO2 rich atmosphere and delivered from outside, the amount may be too low for the origin of life.
AB: Since many astrobiologists are currently examining hydrothermal vents, in search of extremophiles, does the prebiotic chemistry actually get decomposed rather than enhanced by the presence of such ocean venting?
SM: Locating extremophiles is not relevant to the synthesis of organic compounds necessary for life, as the conditions of such ocean venting decomposes rather than enhances prebiotic chemistry.
AB: It has been reported that you had your first results within a matter of weeks, while Urey thought the original electrode experiments might exceed the limits of a 3-year degree program. Was the initial success due to the hint of using a reducing atmosphere or were there other parts of the rapid progress that surprised you?
SM: A reducing atmosphere was definitely the key, resulting first in the water turning red overnight, and after time continuing to change colors as synthesis of organic compounds proceeded. I never had any doubts about the outcome, but I was surprised at the efficiency of the synthesis.
 | | Miller's classic experimental setup, with a simulated ocean, lightning and broth of hydrogen, methane, ammonia and water. |
AB: Have you followed the methanogen research at all? It seems that the use of methane as a precursor was very important to the original experiments, and presumably the progress in methanogens provide some prospecting hints for astrobiologists.
SM: Methanogens appear to be a very ancient form of life, but their biology tell us nothing about the origin of the first biological system. I am sure once they evolved they begun contributing to the methane budget of the Archean atmosphere, however my concerns regarding the reducing atmosphere refer to the period before the origin of methanogenes themselves.
AB: Since this is also the fiftieth anniversary of the Watson-Crick publication, how would you characterize the 13 of 20 amino acids that can be synthesized prebiotically with the complexity of living cells manufacturing proteins from DNA? Is there a bridge that time has clarified there?
SM: Different researchers have different opinions about what is a prebiotic synthesis, but I do not think that there is yet a good prebiotic synthesis of arginine, lysine, and histidine, and of other biochemical compounds.
It is possible of course, that not all them were available in the primitive soup, and that some were synthesized by cells once they evolved. This would require the appearance of biosynthetic pathways, and the more complex they are, the more clear it becomes that they could have not appeared until the genome was sufficiently complex to encode for the proper catalysts.
John Oró showed that one could synthesize adenine, one of the nucleobases, with remarkable ease. Of course, we do not know how synthesis of proteins originated, but it is possible that once a catalytic apparatus was in place, some of the more complex amino acids like histidine resulted not from prebiotic synthesis, but from ancient metabolic pathways. What's Next There are other hurdles in the progression from simple molecules to complex life that are large research topics. Producing amino acids and nucleotides , and getting them to polymerize into proteins and nucleic acids (typically, RNA), are parts of a vast and ongoing 'origins' discussion. But RNA is a relatively fragile component (compared to DNA, or other biomolecules), and thus again its first appearance remains subject to the particular local conditions of the early Earth. To stabilize or catalyze the first biomolecules, clay crystals and vesicle reactions may have helped. No one has been able to synthesize RNA without the help of protein catalysts or nucleic acid templates.
Most scientists now believe that microbes can survive interplanetary journeys ensconced in meteors produced by asteroid impacts on planetary bodies containing life, and this observation has changed a number of the statistical assumptions about where and when biomolecules might first be seeded. Swedish chemist Svante Arrhenius first proposed the notion of interplanetary transport in 1903. However, for life to appear elsewhere, by some similar carbon-based pathway, and then arrive later on Earth means some similar primordial soup needed to be sparked someplace else - perhaps in a reducing atmosphere as Miller first showed fifty years ago. Related Web Pages Miller's 1953 Science paper [PDF 800 kB]
Terrestrial Origins
Entropy and Evolution
What is Life?
Miller-Urey Experiment: Amino Acids from Scratch
The Envelope of Life? Please
Defining Life
Life from Scratch?
Note: Extrasolar Life: [2002-04-26]
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