Problems With The Search For The Origin of Life




Essay II




Chem. 5620.001: The Origins of Life


By: Rami E. Cremesti


Dr. Paul Braterman

University of North Texas
Department of Chemistry


Spring 1998











There are many serious problems and unanswered questions associated with the problem of the origins of life. Some of these problems are inherent and have no solutions, others present a challenge but offer the possibility of a solution given the right kind of research.

In this paper we attempt to address what we consider to be the most important of these problems and try to suggest ways in which they might possibly be solved in the future.


            By 1966 a major change inscientific thought was underway in the origins of life circles. In Philadelphia, in the Wistar Institute, a symposium was held to highlight these changes. It was there that signs of an impending crisis first emerged. Symposium participants came together to discuss the neo-Drawinian theory of evolution. One conclusion, expressed in the words of Murray Eden of MIT, was the need “to relegate the notion of randomness to a minor and non-crucial role” in our theories of origins. This conclusion was based on probability theory, which shows mathematically the odds against the chance formation of the highly complex molecular structure required for life. With the help of high-speed computers, programs could be run which simulated the billions of years process based on the neo-Darwinian model of evolution. The results showed that the complexity of the biochemical world could not have originated by chance even within the time span of ten billion years! Eden’s conclusion was a reasonable if unsettling one.


            Other symposium participants voiced similar views about chance or randomness. V.F. Weiskopf noted, “There is some suspicion that an essential point [about our theories of origins] is still missing”. Eden suggested “new laws” as the missing piece in the puzzle of life’s origin. In his opening remarks as chairman, Nobel Prize laureate biologist Sir Peter Medawar said, “There is a pretty widespread sense of dissatisfaction about what has come to be thought of as the accepted evolutionary theory in the english-speaking world, the so-called neo-Darwinian theory”. It was Marcel Schutzenberger of the University of Paris, however, who intimated the true extent of the developing crisis when he expressed his belief that the problem of origins “cannot be bridged within the current conception of biology”.


            These comments reflect the impotence of chance or randomness as a creative mechanism for life’s origin. But there was dissent too. Some symposium participants, such as C.H. Waddington, balked at this conclusion saying that faulty programming was the problem, not chance. Waddington’s objection illustrates a basic dilemma that has always plagued probability calculations. Such calculations must first assume a plausible chemical pathway, or course of events, and then calculate the probability of the actual course of events. Nevertheless, there is great uncertainty about the actual chemical pathway. As a consequence, calculations showing the extreme improbability that life began by chance ususally have carried little weight with scientists.


            Such probability calculations, however, have now been supplemented by a more definitive type of calculation which does not require a knowledge of the detailed process or exact path of events that led to life. Recent advances in the application of the first and second laws of thermodynamics to living systems provide the basis for these calculations. Through them, accurate probabilities for the spontaneous synthesis of complex chemicals can be calculated without regard to the path that led to their development. All that is needed is information about the initial chemical arrangement and the complex arrangement these chemicals are found to have in living things. These thermodynamic calculations have agreed in order of magnitude with earlier path-dependant probability calculations. For example, some investigators, including Ilya Prigogine, the Nobel Prize-winning thermodynamicist, have relied upon calculations based on equilibrium thermodynamics to show the probability that life occurred spontaneously. Prigogine et al. put it this way:


            The probability that at ordinary tenperatures a macroscopic number of molecules is assembled to give rise to the highly ordered structures and to the coordinated functions characterizing living organisms is vanishingly small. The idea of spontaneous genesis of life in its present form is therefore highly improbable even on the scale of the billions of years during which prebiotic evolution occurred.


                The agreement between the two types of probability calculations has heightened the growing awareness of a crisis in the chemistry of origins.


            There are many other problems too…


            Concentrations of some of the most important early atmosphere components would have been diminished by short wavelength (i.e. <2000Å) ultraviolet photodissociation. Atmospheric methane would have polymerized and fallen into the ocean as more complicated hydrocarbons, perhaps forming an oil slick 1-10m deep over the surface of the earth. If this occurred, very small concentrations of methane would have remained in the atmosphere. About 99% of the atmospheric formaldehyde would have been quickly degraded to carbon monoxide and hydrogen by photolysis. Ammonia photolysis to nitrogen and hydrogen would have occurred very quickly, reducing its atmospheric concentration to so small a value that it could have played no important role in chemical evolution. Some recent studies suggest that, through UV photolysis of water vapor, atmospheric oxygen did reach an appreciable fraction (about 1%) of today’s concentration in early earth times. If the early earth had strongly oxidizing conditions with molecular oxygen present, then spontaneous chemical evolution was impossible.


            It has been assumed that electrical activity on the primitive earth would have been comparable to that of today and many simulation experiments have been carried out using electrical sparks as sources of energy. If the early earth were some 20ºC cooler than today because of less solar luminosity (astronomical theory), however, it would significantly reduce thunderstorms on the earth, perhaps by a factor of 100 or more. This is due to the fact that less thermal energy is availabe to evaporate liquid bodies of water.

Thus, electrical sources of energy have been given overdue importance in the current theories of origins.


  Many experiments have been done on the formation of amino acids under simulated prebiotic conditions and have suggested that they were readily formed on the primitive earth. These results cannot, however, be construed to mean that the question of the origin of amino acids is solved and perhaps does not deserve any more attention.


            Several aspects of this problem need further study. Many of the amino acids formed by the action of electrical discharges, ultraviolet light, heat, or shock waves do not occur naturally in biological material. Why were only twenty amino acids incorporated in natural proteins? In addition, further experimentation is required to establish the synthesis of some of the naturally occuring amino acids which have not yet been prepared otherwise than from organic material.


            An objective of paramount importance in prebiotic chemistry is to understand how nucleic acids, which are at the very core of genetic organization, appeared before life. A glimpse into the manner in which the single units of the DNA and RNA molecule came about is a first step towards this goal.


   In DNA, there are four bases: adenine, guanine, cytosine and thymine. In RNA, uracil replaces thymine. The possibility of the prebiotic origin of adenine has been demonstrated by Juan Oro, working at the University of Houston, and Ponnamperuna. However, despite the many efforts that have been made, the other purines have not been identified in the end-products of experiments with primordial atmospheres. Similar efforts to locate pyrimidines have been very unrewarding.


In order to circumvent this difficulty, many experiments have been attempted to reconstruct cytosine, thymine, and uracil from molecules which may be regarded as second-generation precursors. Some of the end-products of the primitive atmosphere experiments would themselves be the stepping stones to further synthesis. Noteworthy is the work of Leslie Orgel at the Salk Institute. He regarded cyanoacetylene, which is formed when methane and nitrogen are exposed to an electric discharge, as a possible precursor of the pyrimidines. When cyanoacetylene and urea are heated together, cytosine is produced. Urea occurs as a predominant product in most experiments involving methane, ammonia and water. The combination of cyanoacetylene and urea may provide a reasonable pathway for pyrimidine synthesis.




But what if polypeptides and biopolymers had formed in the prebiotic soup? What would their fate have been? In general, the half-lives of these polymers in contact with water are of the order of days and months—time spans which are surely geologically insignificant. In addition, hydrolysis would have destroyed many amino acids. In acid solution, hydrolysis would consume most of the tryptophan, and some of the serine and threonine. Further, acid hydrolysis would convert cysteine to cystine, and would deamidate glutamine and asparagine. On the other hand, hydrolysis would destroy serine, threonine, cystine, cysteine and arginine in the alkaline solution generally regarded to have characterized the early ocean. An alkaline solution would also have caused several deamidations. Thus, both in the atmosphere and in the various water basins of the primitive earth, many destructive interactions would have so vastly diminished, if not altogether consumed, essential precursor chemicals, that chemical evolution rates would have been negligible. The soup would have been too dilute for direct polymerization to occur. Even local ponds for concentrating soup ingredients would have met with the same problem.



Other criticisms are of prebiotic simulation experiments. First, if they truly simulated early earth conditions and processes, we should not expect any meaningful results within laboratory time. Millions of years of simulation might be required for any detectable progress. Second, this method would obscure the complex chemical interactions sought for observation by allowing literally thousands of different reactions to go on simultaneously. This points out the need for a method of partitioning or isolating the various chemical reactions. Only through such partitioning can we gain clues as to the mechanisms involved in the production of life. So we would predictably learn nothing of consequence from a “Synthesis in the Whole” approach.


  What we need is some technique which would allow us to single out individual reaction processes in our simulated “prebiotic soup” and thus follow their progress. Such an approach would allow us to say something meaningful about the mechanism that might have been involved in the pathway to life, and also about the validity of the proposed scheme itself.


            In addition, for a laboratory simulation experiment to be of practical value, some technique must be used to overcome the factor of millions of years of time. Somehow, we must speed up the process so that, like time-lapse photography, we are able to effectively compress the happenings of a long time span into manageable laboratory time, yet without distortion.


            In fact, it is widely accepted today that a technique is available for simulating the extended time factor and for charting the progress of individual chemical reactions. The technique consists of carefully selecting and purifying chemicals conceived to have been the probable precursors of life and subjecting them in mixture to geochemically plausible conditions of heat, light, temperature, concentration, pH, etc.




Another major problem with the the search for the origin of life is the deficiency of the geological record, a deficiency which, just as in human history, grows stronger the further one goes back in time. For this reason, it is believed that all the possibilities for further research will eventually be known in a aschematic and incomplete way only.





            Thermodynamics is another field that disagrees with the theory of  chemical evolution. Systems near equilibrium (like a prebiotic soup) can never produce the degree of complexity intrinsic in living systems. Instead, they will move spontaneously toward maximizing entropy or randomness. Even the postulate of long time periods does not solve the problem, as “time’s arow” (the second law of thermodynamics) points in the wrong direction; i.e. toward equilibrium. Thus, reversing “time’s arrow” is what chemical evolution is all about, and this will not occur in isolated or closed systems near equilibrium.


                        The possibilities are potentially more promising, however, if one considers a system subjected to energy flow which may maintain it far from equilibrium, and its associated disorder. Such a system is said to be a constrained system, in contrast to a system at or near equilibrium which is unconstrained. This is just in theory though. In existing living systems, the coupling of the energy flow to the organizing “work” occurs through the metabolic motor of DNA, enzymes, etc. This is analogous to an automobile converting the chemical energy in gasoline into mechanical torque on the wheels. We can give a thermodynamic account of how life’s metabolic motor works. The origin of the metabolic motor (DNA, enzymes, etc.) itself, however, is more difficult to explain thermodynamically, since a mechanism of coupling the energy flow to the organizing work is unknown for prebiological systems. Nicolis and Prigogine summarize the problem in this way:


                                    Needless to say, these simple remarks cannot suffice to solve the problem of biological order. One would like not only to establish that the second law (dSI ³0) is compatible with a decrease in overall entropy (dS<0), but also to indicate the mechanisms responsible for the emergence and maintenance of coherent states.



Many authors are coming to believe that it is becoming clear that however life began on earth, the usually conceived notion that life emerged from an oceanic soup of organic chemicals is an implausible hypothesis. Some authors believe it is fair to call this scenario “the myth of the prebiotic soup”.


Another gap that has not been bridged in origins-of-life theories is that of the transition between the nonliving and the living: the formation of the first protocells.

The great chasm in our knowledge of the molecule-to-cell transition means scientists are free to speculate in many directions. It is not surprising then to see a wide variety of candidates for protocell systems. Some of these are:


1.      Microspheres (Fox and Dose)

2.      Coacervates (Oparin)

3.      “Jeewanu” (Bahadur)

4.      NH4CN microspherules (Labadie et al.)

5.      “Sulphobes” or “Plasmogeny” (Herrera)

6.      NH4SCN-HCHO microstructures (Folsome et al.)

7.      Organic microstructures (Folsome et al.)

8.      Melanoidin and aldocyanoin microspheres (Kenyon and Nisenbaum), and

9.      Lipid vesicles (Deamer and Oro, Stillwell)


In 1976, Kenyon and Nissenbaum listed the protocells known at that time (numbers 1-7) and then commented:


            Although each of the proposed model systems exhibits some rudimentsry properties of chemical evolutionary interest, it must be emphasized that a very large gap separates the most complex model systems from the simplest contemporary living cells. Moreover, the geochemical plausibility of many of these “protocell” models is open to serious question.


Also, the use of high concentrations of selected organic chemicals in the laboratory production of protocells versus the greatly diminished concentrations expected in the ancient geological setting prompted Kenyon and Nissenbaum to comment that “…the geochemical plausibility of many of these ‘protocell’ models is open to serious question.” Several examples will illustrate the implausibility concerning concentrations necessary to form protocells.


Folsome points out that Fox used 15 grams total weight of amino acids in 375 ml of artificial seawater to produce protenoid microspheres. Therefore, the amino acid concentration would be 0.4M. Claculations regarding formation rates, concentration rates, and thermal and photochemical decomposition rates point to an abundance of amino acids in seawater of no more than about 10-7 M. Thus Fox’s synthesis uses a molar ratio of amino acids to salts that is “10 million times less in the geologically plausible world.”


In the light of the necessary requirements and the conclusions what were previously mentioned, many authors find it difficult to imagine that all the correct chemicals or circumstances to form protocells existed on the early earth. Even if the chemicals did occur, large quantities of configurational entropy work would have to be supplied to form biopolymers and then to organize these into a functional cell. Unless some hitherto unknown principle operated, the availability of such work would have been negligible.


Also, the similarities between the various candidates for models of protocells (mentioned above) and present cells are superficial. For example, coacervates are simply the result of physical forces of attraction, and they are not self-organizing units. They do not contain the structural regularities or selective metabolic processes found in living cells. Likewise, microspheres are simply protenoids attracted together (by physical forces) into a somewhat ordered spherical structure. Here too, the structure is due to the attraction of the hydrophilic parts of the protenoids to water and the hydrophobic parts to each other. Miller and Orgel criticize Fox’s statements relating microspheres to living cells. They state that the microsphere’s bilayer membranes “…are not ‘biological-like’ membranes since they do not contain lipids or carry out any of the functions of biological membranes”. Folsome describes the membranes of micrspheres as “more closely [resembling] a nearly impermeable cell wall or spore coat than a cell membrane.”  Lipid vesicles are criticized from the viewpoint of the concentration gap (experimental versus geologically plausible). Also, the structures formed are relatively unstable, and quite sensitive to ionic environment and temperature.




            In summary, these arguments show that the protocell systems are only conglomerations of organic molecules that provide no genuine steps to bridge the gap between living and nonliving. Furthermore, most protocells are highly unstable and were formed under nongeological conditions.



            Finally, we conclude by stating that a major conclusion to be drawn from the above arguments is that the undirected flow of energy through a primordial atmosphere and ocean is at present a woefully inadequate explanation for the incredible complexity associated with even simple living organisms, and is probably wrong. However, in a strict technical sense, chemical evolution cannot be falsified because it is not falsifiable. Chemical evolution is an attempt at a speculative reconstruction of a unique past event, and cannot therefore be tested against recurring nature. The theory has been accepted very widely, if not generally, by the scientific community. Because of the fact that chemical evolution cannot be falsified, however, its apparent plausibility can easily be exaggerated beyond its true status as speculation and be regarded instead as knowledge.











1.      The Mystery of Life’s Origin-Reassessing Current Theories, C.B. Thaxton, W.L. Bradley and R.L. Olsen, Lewis and Stanly,1992.


2.      The Origins of Life, Cyril Ponnamperuma, E.P. Dutton,  1972


3.      The Origin of Life by Natural Causes, M.G. Rutten, Elsevier Publishing Co., 1972