**1. Introduction**

The origin and the meaning of life on the earth was traditionally attributed to an intelligent creator as an independent act until 1859 when Charles Darwin compiled the book The Origin of Species (Darwin, 1859). In this book Darwin introduced the *theory of evolution by natural selection* (Figure 1, central panel) opening a new perspective to read what looks like the *largest experiment on earth* called biological life. This new perspective has proposed a reversal of the traditional view where the intelligence is placed above the experiment by introducing the concept of *transformation or evolution* (Dennett, 2009). In this upside down view intelligence is not excluded but, rather, is within the experiment and drives the so called "struggle for life" in a dynamic planet where habitats are continuously destroyed and created.

Interestingly some years before, the *idea of transformation* was anticipated by the poet Johann Wolfgang von Goethe. In his book "The Metamorphosis of Plants" originally published in 1790, he wrote: *"Everyone who observes the growth of plants, even superficially will notice that certain*

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*external parts of them become transformed at times and go over into the forms of the contiguous parts" (von Goethe, 1790)*. What then seemed merely a poetic yearning on the wonder of nature, indeed, proposed the *transformation of the parties* (Figure 1, left panel) itself as a creative principle instead of a single external creative act. This *imaginative vision* provided by a poet shows how intuition and imagination can be a source of inspiration in the search for new knowledge and a place of convergence between literature and science (Pelaprat and Cole, 2011). The extension of the concept of transformation from the plant to the animal kingdom and the theory of evolution are further insights undertaken by non-poets with great imagination which certainly meets the definition of *creative scientists* (Boxenbaum, 1991). Thus, in the progress of human knowledge, the claim that science is superior to the literature, simply because it has to do with *facts* and the literature with *imagination*, has no basis because the idea behind every (great) scientific discovery is inspired by intuition, a kind of ability that does not use inference or reason (Beveridge, 1957).

Small cameos representing the faces of visionary scientists who introduced the concepts of transformation, evolution and inheritance.

#### **Figure 1.** The visionary scientists

Looking now at biological life with imagination, it is clear how it may seem the largest experiment, at least, on earth since, till now, we do not know whether there are other ongoing experiments like this in the *universe*. We know that many attempts to search for other forms of life in the universe have been made since the Sixties but, to date, without significant results (Wilson, 2001). Thus we cannot exclude that life on earth is, in fact, the *only* result of a larger experiment that we might call *life in the universe* (Aldiss, 2001).

Returning back on earth, since here the experimental conditions vary continuously because of the regular and irregular environmental changes, there is no certainty about the results. If we try to define the experiment, this could be in summary to *assess life on earth*, and its process, through *trial and error*. Assuming that the experiment is started, to ensure its continuity in the presence of *errors* that can result from an *unfavorable interaction with the environment*, the method to explain how it works proposed by evolutionists implies a kind of continuous refinement of life through the *adaptation process* in order to get the possibility of a new trial with the envi‐ ronment. And it works since this challenge goes on from the evolution of the first *living organism,* represented by *ancestral bacteria,* dated about 3,500 millions of years ago till now (Kutschera, 2009).

*external parts of them become transformed at times and go over into the forms of the contiguous parts" (von Goethe, 1790)*. What then seemed merely a poetic yearning on the wonder of nature, indeed, proposed the *transformation of the parties* (Figure 1, left panel) itself as a creative principle instead of a single external creative act. This *imaginative vision* provided by a poet shows how intuition and imagination can be a source of inspiration in the search for new knowledge and a place of convergence between literature and science (Pelaprat and Cole, 2011). The extension of the concept of transformation from the plant to the animal kingdom and the theory of evolution are further insights undertaken by non-poets with great imagination which certainly meets the definition of *creative scientists* (Boxenbaum, 1991). Thus, in the progress of human knowledge, the claim that science is superior to the literature, simply because it has to do with *facts* and the literature with *imagination*, has no basis because the idea behind every (great) scientific discovery is inspired by intuition, a kind of ability that does not use inference or

Small cameos representing the faces of visionary scientists who introduced the concepts of transformation, evolution

Looking now at biological life with imagination, it is clear how it may seem the largest experiment, at least, on earth since, till now, we do not know whether there are other ongoing experiments like this in the *universe*. We know that many attempts to search for other forms of life in the universe have been made since the Sixties but, to date, without significant results (Wilson, 2001). Thus we cannot exclude that life on earth is, in fact, the *only* result of a larger

experiment that we might call *life in the universe* (Aldiss, 2001).

reason (Beveridge, 1957).

644 Regenerative Medicine and Tissue Engineering

and inheritance.

**Figure 1.** The visionary scientists

Especially under adverse environmental condition, consisting mainly in climatic changes, a better adaptation to the environment obviously increases the chances of survival and gives continuity to the experiment. Therefore is the fittest organism that survives, which is to be considered a *prototype* that has passed the compatibility test with the environment, a process described by evolutionists as *natural selection*. In this framework it is logical to assume that allocating resources for adaptive processes in order to buffer environmental changes is an essential condition for life. The survival obtained through adaptation is temporary because it depends on each organism's life cycle and ends with death. To date the death still represents an essential phase in the experiment of organic life as it is the natural end of each life cycle; in addition, since the dead organism undergoes, under appropriate environmental conditions, to decomposition into basic elements, it can therefore be claimed that death, and after-death processes, also promote the accessibility of the basic elements for the vital functions of the other still living organisms that represent the ecosystem of the earth (Marschner and Kalbitz, 2003).

In order to overcome the time constraints imposed by the life cycle of individual organisms and ensure continuity to the experiment is required to introduce *the possibility of an offspring* and thus to apply the adaptation processes on a population consisting of copies (n>1) of the same organism.

This result can be achieved by duplication, a simple biosynthetic way to keep track of itself by division in use in *prokariotic* cells. Thus duplication ensures continuity to a single prototype, but this is not enough to respond to *major climate changes* of the earth, whose major effects can be deducted from the rate of extinction of living organisms (Jablonsky, 1994; Raup and Sepkoski, 1982).

In such dramatic context it is obvious that having more prototypes of living organisms to be tested provides more guarantees of continuity to the experiment. Therefore the *evolution of species* from a common ancestor, placed at the origin of what is commonly called the *tree of life*, is a way to adapt the biological life to randomly environmental changes (Kussell and Leibler, 2005) and must be seen as a *necessity* in evolution. Emerging of *diversity* is linked to the evolution of the *eukaryotic cell*, representing a real breakthrough in cell organization and function, which occurred about 2,500 million years ago. In this cell has its origin the *endosym‐ biosis*, an advanced form of *phagocytosis*that consists in *using the competence* of other organisms, instead of the energy, to re-organize cellular functions more efficiently, a starting point for the evolution of the cellular organization and *multicellularity* (Figura 2).

Electron microscopy image of a lymphocyte (courtesy of Paola Braidotti, BSc). The subcellular organelles with clear analogies with organs and/or apparati of complex multicellular organisms, such as humans, have been highlighted with pseudo-colors.

#### **Figure 2.** The cell: a body in miniature

Diversity is at the origin of the eukaryotic cell that adopts very early the *meiosis*, a new biosynthetic procedure evolved from the *mitosis* (Wilkins and Holliday, 2009) that allows *reproduction* instead of simply *duplication*. Intimately related to the development of *sexual reproductive cycles* (Antonovics et al., 2011) the *mitosis* generates more variability thus contri‐ buting to the overall *diversity*.

All these *adaptive responses* are coordinated by an *expert program* that enables living organisms to interact with the environment in an *active manner* ensuring at the same time *continuity* and *change* in the subsequent generations. This program, while remaining substantially the same over time, has ferried the biological life on earth through five *mass extinctions*, defined as times when the Earth loses more than three-quarters of its species, namely Ordovician, Devonian, Permian, Triassic and Cretaceous Periods. The *size of the experiment* has changed over time, from the first life forms to *complex organisms*, through the same basic mechanisms, showing the *major cellular evolution* at the origins followed by a very rapid expansion of life forms and a substantial stasis (Cavalier-Smith, 2006) but to understand the general principle by which the program reproduces itself, we will have to wait for some experiments on peas. A few years after the publication of The Origin of Species, Gregor Mendel, trying to understand with his experiments what any good farmer knows, which consists in the fact that through the selection of varieties of plants and their interbreeding is possible to obtain a better product, introduced the general principles of heredity (1866). His remarks were neglected until the early twentieth century when they provided the inspiration for the birth of *genetics*, the study of *heredity in biology* (Figure 1, right panel).

The term genetics was first used by William Bateson in 1905, but to identify the program code that at this point can be called *genetic program*, and how it is transmitted we should wait until 1953 in which the structure of DNA is discovered by other scientists with great imagination James D. Watson and Francis Crick. The rest is a more recent history. Having cracked the DNA code of humans and other living organisms, all scientists facing the incredibly high level of homology between different species have turned their interest towards the *proteome*, opening the so-called *post-genomic era* (Gromov and Celis, 2000). This new branch aimed at the analysis of the *functional state of the genome* has begun to develop. Unlike the genome, the proteome is much more complex and dynamic, and undergoes radical changes both in ontogeny and in different states. The proteome of any cell is unique and provides qualitative and quantitative information on proteins, thus giving a dynamic picture of genome expression under varying conditions (Gromov and Celis, 2000). The post-genomic era, in fact, strengthens the bonds of evolutionary biology with Darwin's theory of natural selection recovering the role of the environment in the experiment. But natural selection is still a mechanism at work? Yes it is, more in some geographical areas than in others (Stajich and Hahn, 2005), but is also working in a quite novel ways through the effects of changes in the environment caused by the so-called modernization (Hunter, 2007).

Although the question of the *origins of the life* after Darwin has been removed or limited in certain areas of science simply confining the *teleological question* to a purely human level (Ayala, 1999), we believe that the mission of modern science is still to find teleological explanations to everything that is humanly intelligible.

Even if none of us can be considered an expert on the origin of life on earth because of the lack of *fossil evidence*, the new synthetic view including *evolution* and *genetics* has contributed to define the main lines along which the *life experiment* on earth has evolved in a continuously *changing environment* (Graham, 2011). Trying to *conceptualize* the main steps in the evolution of *complex organisms*, we can identify three main lines, the first is the *organization* the second is the *diversity* and the third is the *adaptation*.
