1. Mother Planet and Prebiotic Chemistry

Over 100 years ago Nobel Laureate Svante Arrhenius (1908/2009) detailed a comprehensive theory explaining the origins and dispersal of life throughout the cosmos, which he believed did not originate on Earth. Nobel Laureate Francis Crick (Crick, 1981; Crick and Orgel 1973), came to similar conclusions and devised a theory known today as "directed panspermia." Over the ensuing decades numerous scientists have embraced the theory of panspermia (Burchell, 2010; Joseph, 2009a; Rampelotto, 2009); i.e. that life on Earth came from other planets and arrived on our planet deep within asteroids, meteors, and planetary debris.

And yet, although some scientists have concluded that DNA-based life must have had its start at least 10 billion years ago (Joseph and Schild 2010; Sharov 2010), perhaps leading to primitive extraterrestrial riboorganisms which once on Earth kicked started the putative RNA world (José et al., 2010), no one has been able to explain how life began; though a variety of scenarios have been put forward (Glavin and Dworkin, 2009; González-Díaz, 2010; Istock. 2010; Menor-Salván, 2009; Sidharth, 2009; Yanagawa, 1991).

Early researchers (Miller, 1953; Oro and Kimball, 1961) demonstrated how to generate amino acids and nucleic acids artificially. Something vaguely resembling a cell membrane has been artificially generated in a high-pressure chamber. (Yanagawa, 1991). Nevertheless, scientists are still unable to even generate a cell from elements in vitro and no one has ever created life-from non-life (see Ricardo and Szostak, 2009, for comprehensive review of related studies).

The polymerase chain reaction (PCR) (Mullis, 1990) may be the first milestone toward achieving artificial replication of life. However, in PCR, the enzyme is not replicated automatically, though the DNA sequence is. PCR also fails to generate a closed cycle of chemical reactions, which is a hyper-cycle (Eigen, 1992). Based on the belief that metal is prebiotic because of its noncyclic reactions, Joyce and Orgel (1986) demonstrated that various RNA polymers can be generated randomly without enzymes using magnesium ions. Thus in a prebiotic world, metal ions would be necessary for catalyzing the synthesis of RNA polymers.

Unfortunately, researchers have still not found a definite way and principle for generating the minimum hyper-cycle capable of replicating both information and functional molecules. No one has created life, or anything resembling "proto-life" or any type of self-replicating pre-biotic replicon. Most advocates of abiogenesis are not disheartened by these failures. The common reasoning is that chemicals may have been randomly mixed together for hundreds of millions of years before sparking life, and that given a similar amount of time in a well equipped laboratory, life could be easily cooked up. And yet, as argued by Crick (1981), even if given billions of years the odds against randomly creating life are insurmountable. Since complex life appeared on this planet by 3.5 billion years ago, with some arguing for the presence of complex life 4.2 billion years ago (Joseph, 2009a), it seems unlikely that a fully formed, self-replicating life form equipped with a universal genetic code could have been fashioned in such a brief period of time; i.e. within 300 million to 900 million years after the Earth was created and during a time of intense heavy bombardment with no protection against UV and gamma rays and powerful solar winds.

Nevertheless, life must have had a beginning, even if it was not on Earth. Therefore, it seems reasonable to shift our focus from the mother planet and instead concentrate on discovering the design diagram for life. There are now numerous clues which point the way.

2. The Origin of Life

To understand life, we must understand its chemical and molecular structure and the interactions which give rise to the basic features characteristic of living organisms. These include the extraction and generation of energy which can be used to perform work, as well as self-replication and the exchange of information.

The inevitability of adenosine triphosphate (ATP) based on adenine as the main energy carrier is still a mystery (Duve, 2005). Adenine is naturally selected as the main energy carrier from among the two types of purines, adenine and guanine. The adenine-uracil pair with a relatively weaker connection would be dropped out among the information carrier candidates due to natural selection. The relatively lower rates of adenine and uracil than the rates of guanine and cytosine observed in the RNA of a number of species cause redundant monomers of ATP and uridine triphosphate (UTP) outside nucleic acids, which reluctantly become energy carriers (Naitoh, 2008a). ATP runoff from RNA resembles the joker (or remaining unmatched queen) in the card game of Old Maid. The mass conservation law reveals one aspect of the question concerning the nature of life. (Fig. 1)

Fig. 1 Adenine and thymine dropped out among the information carrier candidates.

Life on the Earth uses the five bases of adenine (A), guanine (G), cytosine (C), thymine (T), and uracil (U) for information carriers: DNA and RNA. Purines (A and G) have a relatively large size, while pyrimidines (C, T, and U) are small. The asymmetric size ratio of the main rings in purines and pyrimidines of around 3:2 naturally leads to an asymmetric number of types, i.e., “two” types of purines and “three” types of pyrimidines. This is also understood from the mass conservation law with respect to molecular weight (Naitoh, 2001, 2005, 2006, 2008b), that is, from the fact that the main rings of purines have “nine” molecules of carbon and nitrogen, while “six” molecules form the main rings of pyrimidines (see Figure 2).

Some people may feel that there is a trick in this logic. However, all phenomena, including living beings, cannot escape from the constraint of mass conservation. There is also a 2:3 ratio in immune globulins (I_gX). Two types of large immune globulines (I_gM and I_gE) and three small ones (I_gG, I_gD, and I_gA) are naturally selected, as shown in Figure 2 (Naitoh, 2008c).

The frequency ratios of purines and pyrimidines in RNAs are also asymmetric around 2:3 (Naitoh, 2005, 2006, 2008b, 2008c). Let us consider tRNA. An extremely large frequency ratio, say, far larger than 1.5, cannot produce the stem in tRNA, because purine and pyrimidine pairs do not form in the presence of only one type of base. The asymmetric frequency ratios of purines and pyrimidines around 1.5 induce a loop (leaf) in the clover structure in tRNA, because the leaf (loop) has three loci for anti-codon, as shown in Figure 3. These three-dimensional complex structures of RNAs produce functions such as information transfer and replication.

Then, the considerations based on mass conservation law also lead the general inevitability of twenty amino acids. The further thought experiments also reveal the prerequisites underlying the first minimum hypercycle and the first cell (detailed in Naitoh, 2008b, 2008f).

Fig. 2. Similarity between five nitrogenous bases and five immune globulins (I_gXs).

Fig. 3. Relation between leaf size and amino acids.

3. Morphogenic Processes

The electron cloud is not spherical around an atom heavier than helium (He). Thus, a non-spherical electron cloud induces string-like and ring-like molecules in amino acids and nitrogenous bases, although a spherical electron cloud can generate spherical connections of elements. Nitrogenous bases without a spherical electron cloud also generate string-like DNA and RNA. This is an essential principle of chemistry (Naitoh, 2010).

String-like connections of cells can also be seen for non-spherical cells deformed by the force coming from other surrounding cells. Let us consider a cell having a spheroid shape due to such deformation. The spheroid is not spherically symmetric due to its rotating axis. The discrepancy from a perfect sphere, i.e., its scabrous shape, induces a string-like connection of deformed cells, although cells with less deformation connect as a spherical aggregation or a spherical surface aggregation in two- or three-dimensional space (Fig. 4). It should be stressed that there will also be three sub-types of connections: straight strings such as intestines, bifurcation strings such as blood vessels, and spheres such as the heart and tumors (Fig. 5). One of these three types of connections will be chosen based on the deformation rates and the types of molecules lying between cells such as cell adhesion molecules (CAMs) and extracellular matrix (ECM).

An aggregation of long strings (straight strings, rings, and bifurcation strings) will be close to the next larger sphere like yarn waste because of their flexibility. Repeats of strings and spheres are natural, because we can see the repeats from the subatomic system to the cosmic level (Table 1). According to theory, the sphere-like cosmos after the Big Bang consisted of galaxies of coil-like strings, while the spherical Earth had cyclones and hurricanes with string-like vortices and string-like rivers. Moreover, we clarify the morphogenic mechanism controlling the detailed shape of organs such as the brain. The computational fluid dynamics codes used on supercomputers can reconstruct the three-dimensional structures of systems such as the brain, including eyes and nose (Naitoh, 2008d). The law of momentum conservation dominates these processes.

Fig. 4. Two types of aggregations. Upper: sphere, lower: string

Fig. 5. Three types of strings. a: string, b: bifurcation string, c: ring.

Table 1. Spheres and strings at several levels

4. Macroevolution

The size of the genome has been repeatedly duplicated over the course of evolution (Joseph 2009b). The fundamental driving force for increasing the number of genes and the size of the genome, i.e., gene insertion, horizontal gene transfer, intron and transposon activity (Joseph 2009b), includes the enzyme system for DNA transcription and replication, such as DNA polymerases, topoisomerases, helicases, ligases, and primases, because the enzyme system promotes the connection of DNA fragments.

This increase in the DNA length can induces instability in the DNA topology, because decoupling occurs when DNA reaches a certain critical length. Longer strings lead to a larger possibility of decoupling. The important point is that the variation of molecular weights of chromosomes in human beings is similar to that for amino acids (Fig. 6). There is a rule governing how biological macromolecules are cut.

Fig. 6 Macroscopic similarity between chromosomes and amino acids.

Changes in the DNA topology due to decoupling (rings, strings, multi-strings, and specific sex strings) give rise to the various structures of phenotypes in three-dimensional space (Fig. 7). Sudden decoupling of DNA is the driving force for macroevolution.

Fig. 7 Topological changes of DNA and phenotypes (Naitoh, 2009a).

Let us look at the drastic decoupling of DNA in detail. In the prebiotic pool, a small ring of DNA could give rise to the first proto-cell by manufacturing a protective membrane with the DNA hidden inside. This protocell then begins to replicate and increasing its number of genes and its genome, and creating variable copies of itself. These variable copies become proto-bacteria and proto-archae, and then bacteria and archaea, i.e., the origin of cells (See Yanagawa, 1991). This is possible because enzymes in contact with ring-like DNA can produce DNA and proteins stably by simply revolving on the ring, whereas enzymes in systems having string-like DNA must find the other end of the string after departing from one end in order to accomplish the next replication (Fig. 9a). Probability theory tells us the difficulty in finding the other end of string-like DNA.

However, the absence of ends in ring-like DNA also makes it relatively difficult to take in short DNA fragments swimming around the ring-like DNA, because there are no open positions where a short fragment can attach to the ring (Fig. 9b). Overly stable ring-like DNA for specific replication leads to the difficulty of effecting changes, i.e., adaption and evolution. Thus, it is hard for ring-like DNA to produce diverse components such as Golgi bodies and endoplasmic reticula. It should also be noted that string-like DNA results in macroevolution and also death because of the instability at its ends (telomere).

Fig. 8 String-like DNA and ring-like DNA

5. Life Between Subatomic Particles and the Cosmos

There are many similarities between subatomic particles, biological systems, and stars ( (See Naitoh, 2009b, 2010). A typical example is the repetition of spheres and strings described in the foregoing section (Table 1).

There are the other similar points between subatomic, biological, and star systems. The frequency ratio of neutrons and protons in the core of an atom is between 1:1 and about 1.5, which is very similar to that of pyrimidines and purines in nucleic acids (DNA of 1:1, tRNA of 1:1-1.3, rRNA of 1:1-1.5). It is also stressed that a larger atomic core such as that of thorium and larger RNA such as rRNA have a more asymmetric frequency ratio, closer to 1.5. (Naitoh, 2009b.)

Data on the largest known stars in the cosmos also show that their sizes have bimodal frequency peaks in a range of approximately 1,400-2,000 times greater than the sun and of less than 1,000 times (Harper, et al., 2008; Humphreys, 2006). There may be no stars between 1,000 and 1,400 times the size of the sun). This is reminiscent of the bimodal frequency peaks for the sizes of purines and pyrimidines in nucleic acids. These relationships are deserving of further examination.

A synergistic derivation of a baryonic and biological string theory provides considerable insight into the nature of both systems.

6. Discussion on Diversity

The molecular weights of the twenty types of amino acids show a threefold variation between 240 of cysteine as the maximum, and 75 of glycine as the minimum, although that of purines and pyrimidines among nitrogenous bases varies by only about 1.5 times. The frequency ratios of hydrophilic and hydrophobic amino acids in proteins are also more stochastic than those of purines and pyrimidines in nucleic acids. Although there are only five main types of nitrogenous bases in living beings, there are many types of proteins. How is this variety determined?

Information carriers such as DNA are relatively deterministic, because accurate conservation of information is necessary. It is stressed that accurate conservation of information is achieved by the relatively hard structure of DNA. Thus, DNA maintains a certain spiral shape having a fixed width and pitch. In contrast, functional molecules such as proteins and RNA provide a variety of functions targeted to or triggered by environmental changes. This variety of functions which may be expressed are due to the flexible shapes of the molecules. The level of the diversity of molecules is determined by the concept of "hard deterministic" and "soft stochastic."

This concept can be validated by the stochastic determinism, representing new dynamics, at the triple point of the Boltzmann, Langevin, and Schrodinger equations (Naitoh et al., 2008, Naitoh, 2009b, Naitoh, 2010).

Relatively soft molecules such as RNA and proteins show severe local bending with a short wavelength, which leads to the necessity of a smaller observation window, although a larger observation window is sufficient to see the deformation of longer wavelengths in hard DNA (Fig. 8a). The window size must be the minimum wavelength representing the phenomenon, according to the level of softness, which is between the atomic scale and the size of the averaging scale for continuum assumption. When this smaller window is used for averaging, the density and also the other physical variables such as velocity have indeterminacy because of molecular discontinuity (Fig. 8b). The stronger indeterminacy also implies that more types of molecules are possible.

Hard systems such as DNA will experience less deformation, leading to a relatively larger observation window, i.e., a larger representative scale. On the other hand, soft molecules such as RNA and proteins will have large curvature (severe bending) locally, which leads to the necessity of a smaller observation window. As a result, the difference in observation window sizes produces manifold variety.

Fig. 9 Stochastic level related to window size used for averaging. Discrete molecules in nature bring discontinuity in space, which leads to stochasticity, while phenomena are relatively continuous in time. Thus, averaging for time can be regarded as being consistent with the observation window for spatial averaging.

The quantum mechanics of the Schrodinger equation is also based on an indeterminacy principle. The presence of electrons is given in a certain area, not at a deterministic point. This vague viewpoint with indeterminacy shows an outline of a possible solution. We can obtain the vague solution in exchange for abandoning the determinant solution. An important point is generally that the level of indeterminacy determined by the averaging window size implies the level of variety in natural phenomena (Naitoh et al., 2008, Naitoh, 2009b, Naitoh, 2010).

7. Conclusion and Outlook

DNA is not a design diagram, but rather more like a dictionary of life. In this paper, we have shown some recent clues and hypotheses for constructing a design diagram of life. We also qualitatively revealed the spatial inevitability of the bipolar order of symmetry: the left-right asymmetric Watson-Crick base pairs in DNA and symmetric ones in RNA, the asymmetric and symmetric divisions of cells, and the left-right asymmetric liver and symmetric kidneys (Naitoh, 2008b, 2008c, 2008f).

However, it may take a very long time to find a design diagram and also to write a concrete protocol for generating an artificial cell from only fundamental elements. Even so, we need to continue thought experiments based on available scientific data, while searching for life beyond our Earth and also more closely examining the biological systems on the Earth. Fortunately, the human brain wants to know the entirety of who and what we are.

With the Earth beset by environmental problems, it may be too small to continue to support such a huge population of human beings. The time may come when we will have to live somewhere other than on the Earth. Thus, we seek the existence of other life in the Cosmos and also need to check at least whether there is approximately a 2:3 frequency ratio in molecules. We also want to write a common protocol for us and others, which will be necessary to live stably and pleasantly on other planets. Moreover, a synergistic derivation of a baryonic, biological, and galactic string theory will yield a better understanding of these three systems. Such fusion research is expected to be effective, because we cannot see subatomic particles, although biological systems and galaxies are visible.

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