Miller Reports the Synthesis of Amino Acids

Stanley L. Miller synthesized amino acids by combining a mixture of water, hydrogen, methane, and ammonia and exposing it to an electrical spark, thereby demonstrating the possibility of one possible model of the origins of life on Earth.


Summary of Event

The origin of life on Earth has long been an intractable problem for scientists. While most scientists can envision the development of life through geologic time from simple single-cell bacteria to complex mammals by the processes of mutation and natural selection, they have found it most difficult to develop a theory to define how organic materials were first formed and organized into life. This stage in the development of life—before biologic systems arose—is called chemical evolution and occurred between 4.5 and 3.5 billion years ago. Although great advances in genetics and biochemistry have shown the intricate workings of the cell, relatively little light has been shed on the origins of this intricate machinery of the cell. Some experiments, however, have provided important data from which to build a scientific theory of the origin of life. The first of these experiments was the classic work of Stanley L. Miller, published in the journal Science on May 15, 1953. [kw]Miller Reports the Synthesis of Amino Acids (May 15, 1953)
[kw]Synthesis of Amino Acids, Miller Reports the (May 15, 1953)
[kw]Acids, Miller Reports the Synthesis of Amino (May 15, 1953)
Biochemistry;amino acids
Amino acids
Life, origins of
Biochemistry;amino acids
Amino acids
Life, origins of
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Miller, Stanley L.
Urey, Harold C.
Oparin, Aleksandr Ivanovich
Haldane, J. B. S.

Miller worked with Harold C. Urey, a Nobel laureate, on the environments of the early earth. J. B. S. Haldane, a British biochemist, had suggested in 1929 that the earth’s early atmosphere was a reducing one—that it contained no free oxygen. In 1952, Urey published a seminal work in planetology, The Planets, Planets, The (Urey) in which he elaborated on Haldane’s suggestion, and he postulated that the earth had formed from a cold stellar dust cloud. Urey thought that the earth’s primordial atmosphere probably contained elements in the approximate relative abundances found in the solar system and the universe. It had been discovered in 1929 that the sun is approximately 87 percent hydrogen, and by 1935 it was known that hydrogen encompassed the vast majority (92.8 percent) of atoms in the universe. In addition, the ratio of hydrogen to oxygen, nitrogen, or carbon is more than 1500:1.

Urey reasoned that the earth’s early atmosphere contained mostly hydrogen, with the oxygen, nitrogen, and carbon atoms chemically bonded to hydrogen to form water, ammonia, and methane. Most important, free oxygen could not exist in the presence of such an abundance of hydrogen. In contrast, today’s atmosphere contains about 21 percent free oxygen because many of the light hydrogen atoms have escaped Earth’s gravitational field into outer space. As a result, there are not enough hydrogen atoms to bond chemically to all the oxygen, and oxygen has slowly accumulated in the atmosphere.

As early as the mid-1920’s, Aleksandr Ivanovich Oparin, a Russian biochemist, had argued that the organic compounds necessary for life had been built up on the early earth by chemical combinations in a reducing atmosphere. The energy from the sun would have been sufficient to drive the reactions to produce life. Haldane later proposed that the organic compounds would accumulate in the oceans to produce a “dilute organic soup” and that life might have arisen by some unknown process from that mixture of organic compounds.

The Miller-Urey experiment synthesizing amino acids.


Miller combined the ideas of Oparin and Urey and designed a simple, but elegant, experiment. He decided to take the gases presumed to exist in the early atmosphere (water, hydrogen, ammonia, and methane) and expose them to an electrical spark and determine which, if any, organic compounds were formed. To do this, he constructed a relatively simple system, essentially consisting of two Pyrex flasks connected by tubing in a roughly circular pattern. The water and gases in the smaller flask were boiled and the resulting fluid forced through the tubing into a larger flask that contained tungsten electrodes. As the gases passed the electrodes, an electrical spark was generated, and from this larger flask the gases and any other compounds were condensed. The gases were recycled through the system, whereas the organic compounds were trapped in the bottom of the system.

Miller was trying to simulate conditions that prevailed on early Earth. He had to design the system so that results could be attained in only a few weeks. Therefore, he boiled the water to speed up the reactions, even though Urey had suggested the oceans probably did not boil at that period of the earth’s history. Miller chose to use electrical discharge as the energy source, even though it was known that ultraviolet radiation would have provided the most abundant usable energy for the reactions that he sought. Technical difficulties in designing the experimental system to use ultraviolet radiation, however, required that he opt for electrical discharge. Nevertheless, his experimental design essentially reproduced possible conditions near the earth’s origin.

During the one week of operation, Miller extracted and analyzed the residue of compounds at the bottom of the system. The results were truly astounding. He found that numerous organic compounds had, indeed, been formed in only that one week. As much as 15 percent of the carbon (originally in the gas methane) had been combined into organic compounds, and at least 5 percent of the carbon was incorporated into biochemically important compounds. The most important compounds produced were some of the twenty amino acids essential to life on Earth. Miller’s experiment had produced the amino acids glycine, alanine, aspartic acid, glutamic acid, and others.

The formation of amino acids is significant because they are the building blocks of proteins. Proteins consist of a specific sequence of amino acids assembled into a well-defined pattern. Proteins are necessary for life for two reasons: First, they are important structural materials used to build the cells of the body. Second, the enzymes that increase the rate of the multitude of biochemical reactions of life are also proteins. Miller not only had produced proteins in the laboratory but also had shown clearly that the precursors of proteins—the amino acids—were easily formed in a reducing environment with the appropriate energy.

Perhaps the most important aspect of the experiment was the ease with which the amino acids were formed. Of all the thousands of organic compounds that are known to chemists, amino acids were among those that were formed in this simple experiment. This strongly implied that one of the first steps in chemical evolution was not only possible but also highly probable. All that was necessary for the synthesis of amino acids were the common gases of the solar system, a reducing environment, and an appropriate energy source, and all were present on early Earth.



Significance

Miller opened an entirely new field of research with his pioneering experiments. His results showed that much about chemical evolution could be learned by experimentation in the laboratory. As a result, Miller and many others soon tried variations on his original experiment by altering the combination of gases, using other gases, and trying other types of energy sources. Almost all the essential amino acids have been produced in the laboratory experiments as long as the gas mixture was a reducing one. Amino acids cannot be formed in these experiments if free oxygen is present. This clearly implies that free oxygen was not present on the early earth, a conclusion that has been supported by much recent geologic evidence.

At the time of Miller’s first experiments, it was known that amino acids and proteins were key compounds in the biochemistry of life, but the exact role and nature of the nucleic acids were not entirely understood. The work of James D. Watson and Francis Crick elucidated the structure of deoxyribonucleic acid Deoxyribonucleic acid (DNA); later its central role in genetics became clear. Biologists now know that DNA is composed of three components: organic bases (adenine, guanine, cytosine, and thymine), a sugar (deoxyribose), and phosphate. Miller’s work with amino acid synthesis led others to consider a similar approach to the synthesis of nucleic acids.

In 1960, Juan Oró Oró, Juan was able to synthesize adenine, one of the basic components of DNA, from a concentrated solution of hydrogen cyanide and ammonia, both thought to be present on early Earth. Adenine is not only one of the organic bases of DNA but also a component of adenosine triphosphate (ATP), the major energy carrier in the cell. It was also known that the sugar component of DNA—deoxyribose—could be formed from a concentrated solution of formaldehyde, and that the third component of DNA—phosphate—is naturally present on Earth through the weathering of rocks. Thus, Oró and others, using the Miller approach to the study of chemical evolution, had shown that many of the components of DNA could be synthesized from compounds presumed to be present in the primordial atmosphere.

These studies present a starting point from which to build a coherent theory of the origin of life. It is now clear that the precursors of proteins and DNA could have been synthesized on early Earth. One of the great questions about the origin of life is: Which came first, proteins or DNA?

In living systems today, proteins and DNA are intimately linked. The sequence of amino acids in a protein is specified by the sequence of bases in DNA. On the other hand, DNA cannot operate efficiently without enzymes (proteins). This could not have been the case in the beginning. Miller’s classic experiment showed that amino acids were formed quite easily and that a “dilute, organic soup” as envisioned by Haldane could form. Carl Sagan Sagan, Carl calculated that the earth’s oceans would have developed a 1 percent solution of organic compounds in approximately 300 million years, a time interval that is within the almost 1 billion years estimated for chemical evolution. Although the initial assembly of amino acids into proteins is not understood, Miller’s experiments demonstrated that amino acids were probably much easier to form than the precursors of DNA. Adenine could be formed only from highly concentrated solutions of ammonium cyanide, concentrations not likely to be found in the oceans. Thus, Miller’s experiments suggest that proteins may have formed before DNA.

Miller’s work was based upon the presumed composition of the primordial atmosphere of the earth. The composition of this atmosphere was calculated on the basis of the abundance of elements in the universe. If this reasoning is correct, then it is highly likely that there are many other bodies in the universe that have similar atmospheres and are near energy sources similar to the sun. Miller’s experiment strongly suggests that amino acids should have formed on other planets, and perhaps, life as well. Biochemistry;amino acids
Amino acids
Life, origins of



Further Reading

  • Dickerson, Richard E. “Chemical Evolution and the Origin of Life.” Scientific American 239 (September, 1978): 70-86. The author presents clearly the origin of organic compounds and early life as understood by scientists. A detailed summary of chemical evolution gives the layperson an excellent introduction to the subject. Recommended to students with some background in chemistry and biology.
  • Dyson, Freeman. Origins of Life. New York: Cambridge University Press, 1985. An excellent book on the origins of life that outlines clearly the major advances in the study of chemical evolution. The question of whether proteins or DNA arose first is dealt with in some detail.
  • Ferris, James P., and David A. Usher. “Origins of Life.” In Biochemistry, edited by Geoffrey Zubay. 4th ed. Dubuque, Iowa: Wm.C. Brown, 1998. A brief summary written by two knowledgeable participants; the level of discussion requires a background in college chemistry.
  • Luisi, Pier Luigi. The Emergence of Life: From Chemical Origins to Synthetic Biology. New York: Cambridge University Press, 2006. Comprehensive overview and detailed analysis of the development of organic life from inorganic matter. Bibliographic references and index.
  • Oparin, A. I. Origin of Life. 2d ed. New York: Dover, 1953. The classic work on the origin of life by the father of the study of chemical evolution. Recommended for all serious students of the origin of life and for those interested in the history of science.
  • Orgel, L. E. The Origins of Life. New York: John Wiley & Sons, 1973. A well-written overview of the nature and origin of life. Chapter 8 discusses the work of Miller and describes the significance of his results.
  • Ponnamperuma, Cyril. The Origins of Life. New York: E. P. Dutton, 1972. A well-illustrated book written specifically for the layperson. Ponnamperuma is one of the major researchers into chemical evolution and he outlines clearly in chapter 5 the basic work done on the origin of organic compounds.


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