**2. The organization**

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

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‐

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

with pseudo-colors.

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

646 Regenerative Medicine and Tissue Engineering

buting to the overall *diversity*.

The *organization* or, better, the ability to organize itself, is the main feature of *living organisms*, but to date no one can state with certainty whether this property is intrinsic or acquired during evolution. Geological research has shown that the age of planet earth is about 4,560 million years (Dalrymple, 1991). Thus, as we saw earlier, we will have to wait about 1,000 million years from the origin of the earth for the evolution of the first living organism consisting in *ancestral bacteria* or *archaea*. In this somewhat *obscure* lapse of time, that have lasted at least 3,500 million years, much space is left to the imagination, but it is reasonable to assume that living organisms are endowed with the ability of *self-organization* and that this capability has evolved from elementary properties of chemical compounds essential to kick off life on earth.

This obscure stage has possibly involved *abiotic molecules* slowly evolving towards selfreplicating forms (Paragraph 1) in a kind of *chemical evolution* (Martin and Russell, 2003) that goes beyond this discussion. Self-replicating means keep track of itself and preserving memory of the experiment, but the question is, obviously, about the nature of the first self-replicating molecule; however, since replication is accomplished in modern cells through the cooperative action of *proteins* and *nucleic acids*, there is a general agreement on their essential contribution to the development and maintenance of any living organism. Hence at the origin of the cellular organization are elementary properties that, through self-replication, are transmitted to the offspring.

The appearance of the *prokaryotes* dating back approximately 3,500 million years ago represents the first remarkable result of this process, but is just a step towards the refinement of life. A real breakthrough in cellular organization is the advent of the *eukaryotes* where elementary properties are re-arranged to a higher level of complexity. But, how was it possible? Nobody knows, however this seems to be related to the endosymbiosis, an evolved form of phagocy‐ tosis that consists in using the competence of other organisms, instead of the energy. From this peculiar type of *symbiosis* (Mereschkowsky, 1926) derive certain essential properties of the cellular organization, such as *cooperation*, development of specific skills or *competence*, *complexity increase*, development of *interaction patterns* up to *multicellularity*.

The appearance of multicellular organisms as occurred fairly rapidly in the experiment of life must be seen as an evolutionary stage that does not necessarily involve a significant increase in the complexity of the genetic program (Prochnik et al., 2010); this process has been repro‐ duced recently in vitro by using an eukariotic model (Ratcliff et al., 2012).

Furthermore, since the evolution of multicellularity has not resulted in the replacement of the *prokaryotic prototype* that is still alive, for example, in *modern bacteria*, it seems logical to assume that this stage represents a necessity in evolution (Furusawa and Kaneko, 2000) for *some* living organismsexpeciallywhenexposedtohighlyselectiveenvironmentalconditions.Theseextreme conditionsoneartharepossiblyresponsibleforthe*evolutionarypeaks*recordedafterlongperiods of stasis (Eldredge et al., 2005) and thus for the evolution of multicellularity. At this regard it is noteworthythatarchaeaandbacteria,inspiteoftheirearlyevolution,exibitaverysmallnumber of species (about5,000)if comparedwithmulticellularorganisms,andareassociatedwithahigh levelofresistanceinallecosystems(Staley,2006).Therefore,itisplausibletoassumethatbacteria are a *source of backup* capable of restarting the experiment of life on earth even after catastroph‐ ic climate change or, possibly, in other places in the universe (Wickramasinghe, 2004).

Returning to the metaphor of the *tree of life*, having a common trunk or origin means to share, at least, some features and/or functions, and in multicellularity some properties of unicellular organisms are reallocated on a larger scale with the evolution of *cellular differentiation* and *specialization*. This new kind of cooperation establishes *functional hierarchies* and leads from the development of *finely detailed pattern* up to the evolution of fully developed *complex organ‐ isms*(Furusawa and Kaneko, 2000).

The evolutionary stages, from the development of the first prototype to multicellular organ‐ isms, are conceptualized in the block diagram in Figure 3.

The black box [*new generation* machine] represents the obscure stage of the experiment of life, originating the first prototype [*single organism prototype*]. The environmental tests are possibly responsible for the evolutionary peaks, generating others prototypes [*variations, diversity*] up to multicellular and complex organisms.

**Figure 3.** Conceptualization of evolutionary stages
