The origin of life on Earth is still a mystery – a mystery being a problem which does not appear to have a solution. The general idea about it is the one originally expressed by the Russian chemist Alexander Ivanovic Oparin (Figure 2), who in 1924 proposed that the origin of life was due to natural processes, whereby simple chemicals originally present on Earth underwent a spontaneous process of increased complexity till the formation of the first cells – a process that today we would call of molecular evolution.

Later science added a few notions to the basic Oparin’ idea. Our Earth was a fire ball a little more than 4 billion years ago, but it was already rich of microbes 3.8 perhaps 3.9 billion years ago. The Figure 3 shows the famous first cell fossil, which is 3.8 billion years old. The reconstruction appears to correspond to a modern prokaryotic cell, and if this fossil cell already had a full genome, then life must have started then even before: and this has brought scientists to say that life on Earth started as soon as it was possible, inferring than, that it must have been a rather “easy” process.

If it is so easy, let us do a simple experiment. Let us take a 100-liter water tank, under strict sterile conditions, and add all prebiotic chemical compounds we know of, amino acids, nucleotides, sugars, fatty acids, hydrocarbons, with all salts, and metal ions and all what our terrestrial crust may have possessed. We can add a thermostat, to change the temperature every week or so.

There is the problem of concentration. Our solutions may be too diluted, then let’s make the experiments in double, and in each one of them, let’s evaporate the water periodically, so as to achieve the situation of a lagoon which became dry, producing a very high local concentration of the compounds.

According to Oparin, lightening might have been the energy source to induce reaction among the basic four components of the prebiotic atmosphere, so as to make amino acids. Even if more recent literature has shown that these electrical discharges were not necessary, let us make so, that each thank is provided with electrodes that give electric discharges every few minutes...

Now let us proceed: let us wait, taking out automatically from each thank a few microliters solution to be analytically examined – to see whether some reaction products are being formed. Let’s simply wait. Wouldn’t some protocell appear after a while? If this happened on the prebiotic Earth, why not again?

Why not?

It can be easily predicted that nothing will happen. At the most, one might observe formation of vesicular structures from the originally added fatty acids, but no interesting macromolecular precursors, such as orderly sequences of amino acids or polynucleotides. Perhaps the dry lagoon experiment may give some random polymeric structures, but from them to arrive to life, namely to the mutual interaction between orderly sequences of amino acids and orderly sequences of polynucleotides there is an immense gap. Experiments about the origin of life, conceptually similar to those indicated above, have been conducted by chemists in the last fifty-seventy years in the best university laboratories of the world, utilizing all the ingenuity of modern chemistry knowledge – but to no avail. Self-reproducing protocells, or even protocells in a simple homeostatic regime, have never been obtained. If making life would have been an easy process, scientists would have produced it many times in the laboratory. It never happened.

And the question is then: why not? Why did life not form spontaneously, considering that we have given in the reaction thanks all what Earth had to offer in prebiotic times? The most straightforward explanation is simply that the formation of life is not a thermodynamic spontaneous process. In other terms, we can simply say that the origin of life is not deterministic.

What is the alternative-still remaining in the framework of science? In terms of the classic controversy in the life science, the alternative to determinism is contingency- and most has been written about that over the last fifty years in the field of the origin of life. Contingency (not to be confused with the parent term “chance”) corresponds to the notion by which a given process, instead of going linearly from cause to effect – assumes a zig-zag erratic pathway, due mostly to the changing environmental conditions. A crude representation of the action of contingency has been depicted in the way shown in Figure 5 (Luisi 2016).

Obviously if the construction of a growing structure follows such a chaotic pathway, most of the processes will go to a dead alley, the final product will disappear and there will remain no record in the story of evolution. However, some of these contingency avenues may be useful, where useful means bringing about a stabilization of the structure itself, or constructing a more resilient unity – perhaps even something that is capable of self-reproduction.

One could argue that four billion years ago there were perhaps unknown chemicals, or unknown environmental conditions, that we are not able to repeat today. But this would be explaining a mystery with another mystery. One could also argue that for the origin of life we may be dealing with reactions that need years or centuries to proceed – but this is also not a good argument, as even when reactions have a long induction period, one should be able to see, with our powerful analytical methods, the formation of some initial aggregates.

The acceptance that there is no determinism in the origin of life would account for several things. In a contingency pathway there is no way to predict the causal succession of events, namely there is no predetermined logical connection between one step and the next ones. Even more important than that, is the observation that the origin of life is certainly not due to a single unitarian process: there is no reason for such an assumption, once that we rule out the predetermined plan – we are rather dealing most conceivably with several independent pathways that at a certain point have crossed each other-giving rise to a more complex web of contingent avenues. We need for example to have the formation of the orderly sequences of proteins, and the independent invention of the orderly sequences of nucleic acids, then their mutual interaction, so that the sequence of the one becomes causally dependent from the sequence of the other – with the entire mechanism of self-reproduction; and the entrapment into a membrane. And we neither know how any of these processes originated, nor their interlocking.

This is indeed the core of the problem: not only the scholars of the origin of life have failed so far to reproduce in the laboratory the events which led to the origin of life, but they do not have any scientific hypothesis on how life may have originated. To make things even clearer: in the case, say, of the origin of the universe, we have the theory of the big-bang, which doubtless has points of uncertainty and doubt – but the great majority of scientists stand behind this theory, which accounts for all of most of the cosmic data we know of. For the origin of life, instead, we do not have such a hypothesis – there are some speculations, the most well-known being the “prebiotic RNA-world” – which however, as shown clearly (e.g. Luisi, 2016) does not make any sense from the chemistry point of view. To repeat this point quickly, on why it is a non sense: this hypothesis – in its most basic version – is based on the a priori existence of a RNA molecule which is capable of self-replication. But for having a self-replication you need to have the formation of a RNA dimer, which implies a minimal starting concentration of say, 10-10 M – which in turn would mean, (the Avogadro’ number being what is it, namely 6.02. 1023) that in one liter of that prebiotic soup you would have to have ca. 1013 identical copies of that RNA. This would be equivalent to invoke a miracle, and then there are other theories based on miracles, which are much more accredited.

So, this is the point: not only the experiments with our tanks do not work, despite all possible ingenious variation of two generations of brilliant chemists – but we do not have a conceivable theoretical scheme on paper, on how the origin of life may have come about.

We have to recognize this hard fact. Maybe tomorrow some splendid bio-Einstein will discover the solution – nevertheless, for the moment, we simply don’t have the slightest idea on how life originated from non-life. Which, again, does not mean that we have to give up the research and resign to the existence of a mystery (a mystery is a problem that by definition has no solution). However, it is important to have an honest basis of departure.

Article written in collaboration with Prof. Angelo Merante

Luisi, Pier Luigi, The Emergence of Life, second edition, Cambridge Univ. Press, 2016.