9.1 Searching for Life
Suppose you were an astronaut on a foreign planet, searching for life. What would you actually look for? Of course you have to consider that unknown life may appear in a form which is completely different from all life we know. It may look and function so differently that any comparison with terrestrial forms of life would be impossible. So in your search for life, it does not make sense to look for bushes or trees with green leaves and for crawling insects or spiders. Instead, you have to find markers which reflect the basic principles of life: structural features or processes which indicate “a self-sustaining chemical system capable of Darwinian evolution” which is the NASA’s definition for life [1]. But how to recognize them?
What is the basic principle of life? In 1945, during his exile in Ireland, the Nobel laureate physicist Erwin Schrödinger wrote a book titled What is Life? [2]. In this book, he states that “life decreases or maintains its entropy by feeding on negative entropy.” If we roughly translate “entropy” into “disorder” (see Sect. 3.5), this statement would mean that life is an ordered system which maintains or increases its order by feeding on negative disorder. Schrödinger seems to identify the order as a central parameter for life. So maybe, wandering on the planetary surface, you should look for ordered structures? We know that entropy is a measure for disorder, so looking for order means looking for low entropy. On your field trip to a foreign planet, you of course enjoy the latest and best analytical equipment, so we assume that you carry a portable entropy meter (a device that still needs to be invented). So you stumble over the rugged planetary surface and point your instrument here and there and watch out for low entropy values. Soon you will notice that the readings will be close to zero whenever you find crystalline minerals. Structures like quartz crystals, diamonds, or pieces of salt represent nearly perfect order. With the atoms or ions placed in a regular three-dimensional lattice, they are among the most ordered structures in universe. But are they alive? Of course not. For being alive, they lack the extremely diverse functional units of machinery which are able to undergo metabolism, growth, or reproduction. In other words, they lack complexity. So obviously, order alone is not a sufficient criterion.
So the next day, you try another excursion, this time equipped with a complexity meter (again a device which is still dearly missed in today’s laboratory equipment). Pointing that instrument onto the minerals you found the day before, the needle will hardly move: the building principle of a mineral crystal is generally very simple as it just involves endless repetitions of small elementary units, the so-called elementary cells of the crystalline lattice. So you keep moving across the surface until you suddenly detect high complexity in an amorphous black chunk of material. It was formed from basic organic compounds (which are commonly found on interplanetary bodies such as comets) under the influence of UV radiation over extended periods of time. Under these circumstances, small organic molecules can form chains of variable composition which by themselves can undergo further reactions. Altogether, these reactions lead to extremely complex chemical compositions. In its touch and in its optical appearance, the mixture could resemble common asphalt. Is it alive? Of course not. Even if the material may compete with an organism regarding its chemical complexity, it lacks the structural regularity which is required for the complex functionality of life. In other words, it lacks order.
Now you are at a crucial point. You realize that, in order to be alive, a system has to combine order and complexity. It is exactly this combination which separates dead objects like crystals or asphalt from something like a living bacterial cell. In such a cell, we will find an ordered subcellular structure with membranes, separated internal environments, concentration gradients, and large molecules with well-defined three-dimensional structures. At the same time, the cell is very complex, with thousands of chemical constituents, numerous sets of interdigitated chemical reaction schemes, and a complex chemical memory stored as a genetic code. The order inside the cell and the structural complexity of the cell form a functional unit; one cannot work without the other. So, for a successful search for life, you will have to carry two instruments since you will have to determine two important values simultaneously: order together with complexity. With this in mind, one may try to define the limits of life. Where does it start? What are the limits regarding order and complexity? How can you assign measurable quantities to the order and the complexity of life?
9.2 Life and Order

Different states of a biological cell on a scale of order and disorder. Even the rupture of a single membrane can cause the death of the cell which then crosses the line between life and death (right). A reference value for order is given by the state of a completely homogenized cell (left)
So far we have been looking at static aspects of life. What about processes? Within a living cell, numerous chemical reactions occur simultaneously which are connected to life. These reactions form a complex and well-ordered network with one reaction using the products of another. All these reactions occur in a controlled manner such that accumulations or shortages of reaction components are avoided. How is this reaction network accounted for in terms of order?
We know that every process in universe tends to increase disorder (see Sect. 3.5). Consequently, every chemical process inside the cell basically would have the tendency to drive the state of the cell toward the line of death indicated in Fig. 9.1, and eventually it would kill the cell. So how can the cell survive any process over an extended period of time? How can the cell avoid the seemingly unavoidable death of disorder? The answer was given by Erwin Schrödinger in a somewhat cryptic statement: the cell has to “feed on negative entropy” [2]. But what does that actually mean?
In fact, life has invented the solution to this problem at a very early stage: energy. Life uses energy to create positive entropy, or in other words, disorder in the environment. Chemical energy, as in food, turns into heat, and heat turns into chaotic motion of molecules. However, a fraction of this disorder is taken back, as negative entropy. The chaos induced by burning one gram of sugar, for example, is slightly larger in an open fire than in case of a biological degradation process in a living cell. The difference is exactly the negative entropy the cell is feeding on. With that portion of negative entropy, the cell manages to stay at a constant position of the scale of order and disorder (Fig. 9.1) and allows it to run continuous reaction networks. With the use of energy to create a portion of negative entropy, life has discovered a way to prevent the death of disorder while keeping up the dynamics of metabolic processes.
9.3 Life and Complexity
Regarding complexity, the approach for a quantitative value is much more demanding as many definitions of complexity exist [4]. A very suitable approach to measure complexity was found by the Russian mathematician Andrey Nikolaevich Kolmogorov. According to him, the complexity of a system is determined by the minimal size of a computer program (in bytes) which is necessary to fully describe the system in all its details. If we consider, for example, a crystal with atoms at well-defined positions in space, such a program would be very simple. It would contain the basic building principle of the crystal, the so-called elementary cell, and would just repeat this scheme over and over again. Such a program would just need a few bytes. According to Kolmogorov, the complexity of such a crystal would be very low. Now if we look at the chunk of asphalt on our foreign planet, the situation is very different. With its millions of compounds, many of them chain molecules with various side groups and differing sequences of structural units, a corresponding computer program for its complete description would be quite lengthy: every single compound, practically every single molecular chain, would have to be determined in its full structural detail. With that, the corresponding program code would become very long, easily in the range of megabytes. So, according to Kolmogorov, the complexity of this chunk of asphalt would be extremely high. But how could we define the complexity of life?
In case of life, there is in fact an existing analogy to a computer program. It is the genome, which is actually interpreted and translated into complex molecules such as enzymes and structural proteins. These in turn are responsible for the formation of cell structures as well as for guiding the complex reaction network of the cell’s chemistry. That means that all the complexity we can assign to a living cell corresponds to the complexity of the cell’s genome.
Very similar to a computer program, the information content of the genome can be measured in bits and bytes. In computer technology, a byte measures the information of an eight-digit binary number, which accounts for numbers between 0 and 127. With the DNA strand consisting of four different bases (forming base pairs together with their counterparts, see Sect. 4.2), the same amount of information can be stored in a section of the DNA which is four base pairs long. So the information content of the DNA can be measured in bytes, which, following Kolmogorov’s definition, also measure the initial complexity of the corresponding organism.
It is surprising how little of information is necessary to code simple life. For example, a very simple microorganism called Nanoarchaeum equitans can exist on a genome with only 490,885 base pairs [5]. This corresponds to approximately 123 kbytes, according to the estimation given above. If we consider that a printed page like this one contains something like 2 kbytes of data, this microorganism can live on less than 62 printed pages of information. This is just two or three chapters of the book you are holding in your hands! And there may be even smaller genomes: the lower limit of genome size for living cells has been estimated to be 375,000 base pairs corresponding to approximately 93 kbytes [6]. The human genome, on the other hand, consists of about three billion base pairs with about 809 Mbyte of information. However, only something like 1.5% of this information is actually translated into protein structures, while the vast majority is reserved for regulation of gene expression and for chromosome architecture or may not serve any purpose at all [7]. Therefore, the true value for complexity of the human genome can only be roughly estimated; it may amount to something like 12 to 800 Mbytes. Compared to the genome of the microorganism Nanoarchaeum equitans, the complexity of a human’s genome is at least a hundred times larger. And, in contrast to a simple microorganism, a human accumulates further complexity when growing up. Memory, experience, learning, and growing intelligence add a lot to the original complexity over years of life.
9.4 The Limits of Life

Diagram showing the limits of common biological life according to the criteria of order and complexity [8]. The blue rectangle can be seen as the area of life limited by the minimal order (or reciprocal entropy) and the minimal complexity (or the size of the minimal genome) of a living cell. Everything which falls into this area is either life itself or any product of life like books, software, artificial intelligence, art, or culture. The scaling of this graph is arbitrary
In such a diagram, the results of the first unsuccessful results of your search are easily localized. Crystals exhibit an extremely high degree of order but very little complexity; therefore they are found near the lower right corner of the diagram. On the other hand, the piece of asphalt is extremely high in complexity but very low in order, so it is located near the upper left corner.
The lower limit of life regarding order is defined by the reciprocal entropy of a living cell (vertical broken line in Fig. 9.2). It is this line which is actually crossed when the cell dies, e.g., caused by chemical or mechanical influences. So based on the knowledge we have on present life on earth, this limit is sharp and well defined.
The lower limit of life regarding complexity is somewhat blurry. As mentioned above, the lower limit of information for very primitive cells may be around 93 kbytes [6]. However, the corresponding organisms tend to depend on biomolecules which are present in their environment and sometimes are suspected to be parasites, such as Nanoarchaeum equitans [5]. So it is a question where real independent life may start. Also, there are biological structures which generally are not considered to be alive: viruses. A typical virus carries a genome of about 40 kbytes in size, which is well below the limit of 93 kbytes. However, there are also viruses with a genome as large as 140 kbytes, which would exceed the complexity value for primitive cells. On the other hand, these so-called pandoraviruses are a special case and have even been discussed as a special domain of life [9]. All in all, there is some justification to estimate the lower limit of complexity near 93 kbytes (horizontal broken line in Fig. 9.2).
With these boundaries, we may define a specific area of life. All known structures which, according to biologists, are alive on earth will fall into this section. On the other hand, it seems that every single structure on earth which falls into this section either will be life itself or was created by life in some manner. Products of life in this sense are, e.g., books, computer software, artificial intelligence, pieces of art, the Internet, or science and culture in general. These products can easily be as complex and as ordered as their creators. They may in some cases even exceed their state in terms of order and complexity.
9.5 Consequences for the Origin of Life

Diagram showing the possible pathways toward life according to the criteria of order and complexity [8]. Starting with simple terrestrial chemistry (water, carbon dioxide, methane, etc.), the development went toward early prebiotic chemistry (amino acids, lipids, sugars, etc.). At some point, self-replicating systems were formed which then could undergo Darwinian evolution eventually leading to biological life. Green arrows mark spontaneous processes which are easily achieved. Pathways 1 and 2 are explained in the text. The scaling of this graph is arbitrary
From there, a development toward life means that we have to follow a diagonal line (blue arrow in Fig. 9.3) which in fact is a problem. It is quite easy to advance in a horizontal line which means a mere increase of order: a simple crystallization process by drying or cooling a mixture of chemical components will do this job. It is also quite simple to follow a vertical line, the mere increase of complexity: this could be the consequence of numerous uncontrolled chemical reactions, e.g., induced by ultraviolet light. But it is in fact very difficult to simultaneously increase order and complexity, that is, to advance along the diagonal of this graph.
The most powerful approach for the diagonal pathway is in fact Darwinian evolution. It proceeds in very small steps of small random changes followed by selection which in our diagram would appear as a narrow zigzag, hardly deviating from a diagonal straight line increasing order and complexity. On this path, evolution has led from single cells to higher organisms and ultimately even to a brain which is capable of self-reflection.
Darwinian evolution is in fact a very powerful process, but it generally requires a self-replicating system which has some sort of a structural memory, for example, a genome, which is being copied from generation to generation. Several theories have been developed on how such a process may occur on a molecular level and how it can lead to molecular evolution. The most prominent example may be the RNA world [10] (see Chap. 6), but there are also alternative ideas like an interaction between RNA strands and peptides [11] (see also Chap. 8). In any case, it needs a relatively high degree of molecular development. So how could the basis for molecular evolution, the stage of self-replicating molecules, be reached?
- 1.
Systems which initially increase complexity and then gain order in a second step. Typically, a very large number of chain molecules with different sequences are formed in a random process (the state of high complexity) which then undergo rigid selection until a small number of “successful” chain molecules with distinct sequences are left (a state of reduced complexity but of higher order). A good example for this pathway 1 would be the formation and selection of peptides as described in Sect. 7.4.
- 2.
Systems which initially increase order and then gain complexity in a second step. A typical example for this pathway 2 would be a process which starts on a mineral surface [12] (a state of high order) and then is getting transferred into a liquid or cellular environment (a state of reduced order but increased complexity).
So, there are in fact known molecular mechanisms which lead from simple, disordered states to complex and ordered states. It is now the challenge for the field of prebiotic chemistry to discover and identify them and to reproduce them experimentally.
Back to your role to search for life on a foreign planet: how could you recognize very early steps in the formation of life? This is a much more difficult task than just finding life, since you would not only have to look for states but you would have to look for slow developments. You would have to search for processes like the ones just mentioned (1 and 2) which lead into a pathway of increasing order and complexity. Actually, this is something one should try to do on earth as well: can we discover terrestrial processes which have this potential? If we identify such a process, we would indeed have come a large step closer toward understanding the true origin of life.