Randomness and nondeterminism: from genes to free will with implications for psychiatry

Randomness and selection are fundamental processes rooted in the very basis of life, as postulated by the theory of evolution. First, mutations are randomly and continuously fed in the gene pool of a population (on average 175 mutations per diploid genome per generation), creating and maintaining over time a high level of genetic diversity.1 Second, this gen etic diversity is subjected to differential survival and reproduction of individuals facing diverse and often unpredictable environments. This differential fitness is the basic mechanism of natural selection and evolution, a quintessential pillar of modern biology. In addition to the large number of genetic variations generated by mutations, sexual reproduction (by far the most common mode of reproduction) and recombination are associated with the generation of an enormous amount of genetic variations among individuals.2 During parental meiosis, grandparental chromosomes are randomly recombined (on average 1.57 random recombinations for each pair of parental chromosomes, leading to billions of different gametes).2 The random assortment of 2 of these gametes (1 from each parent) forms the zygote, which will then develop to become a unique individual. The ubiquity of sexual reproduction and recombination, despite the heavy burden associated with this mode of reproduction compared with asexual reproduction (the so-called Sex Paradox), strongly suggests that the processes of generating random variability followed by selection strategies are fundamental to how life starts and thrives. Consequently, all beings conceived via sexual reproduction start life with a toss of genetic dice and are subsequently posted to undergo the trials of life. Remarkably, these fundamental principles of random generation of variations followed by selection seem to be at odds with how we think and conduct biological research. Indeed, our natural reflexes as scientists, are to study “deterministic mechanisms.” Noise and randomness are antithetical to our experimental designs. The dogma in biology stipulates that the genome, once assembled, is the blueprint of development, which is a deterministic process, the cogs of which we try to discover in our laboratories. Of course, this deterministic model allows for environmental contingencies to play a role on how development proceeds, but these are also conceived as deterministic processes. Notwithstanding the importance of deterministic mechanisms and their role in psychiatric research,3 and in the view of the random nature of how beings enter life, as discussed above, should we not expect that the same processes of randomness followed by some kind of selection should be present at all levels of biology and beyond? In this editorial, we argue that the initial tosses of dice that inaugurate life “will never abolish chance,” echoing the title of Mallarmé’s famous poem. We will show that randomness is ubiquitous throughout the life cycle and at all levels of analyses. Taking examples from recent developments in molecular biology, neuroscience, psychology and philosophy, we argue that these processes — randomness and selection — are at play at all these levels and may be fundamental to our understanding of complex phenotypes such as psychiatric disorders. Our constant failure to consider these basic aspects of biology and psychology may be at the roots of our chronic struggle to fit mental life in a deterministic framework, however important this framework is.