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So what is a gene?

Author: Ken Richardson Publisher: https://www.bps.org.uk/psychologist/so-what-gene Publish Date: 2016-3-23 Review Date: Status:đŸ’„

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  • The models of reality that scientists create have tremendous influence over us. Quite rightly, too - at least for most things. But many models – especially in the human sciences - are tentative constructs with foundations in everyday experience. Because of that, overturning them often has ramifications far beyond science itself

  • Note: which is why medicine entertwines science and ethics in a sketchy way

  • Such was the model of the universe rotating around the earth. Astronomers reported what seemed so “obvious” to everyone. And religious authorities said so, anyway. Moreover, the geo-centric order of the universe seemed to legitimise the centralised nature of social powers – of rank and privilege - on earth. In sum, a useful ideology that held sway for hundreds of years. Eventually, of course, it crumbled under the weight of counter-evidence and the radical alternative fashioned by Copernicus, Galileo and Newton. But with that came the stirring of inquiry into the legitimacy of the whole class structure of society, the authority of the church as arbiter of truth, the Divine Right of Kings, and so on. The ripples spread through, politics, philosophy, science, art, music, and psychology. No wonder it was bitterly resisted.

  • It was by no means the end of scientific legitimation of ideology, however. In the 20th century the geo-centric frame of reference seems to have been replaced by a “geno-centric” one: the gene has taken the place of divine order as determinant of rank and privilege. So a kind of “gene god” is venerated today as an entity with almost supernatural powers: the roots of creation, the ordering principle of life, the design of all that we are, and the roots of our individual differences in mental as well as physical traits

  • In her book, The Ontogeny of Information, Susan Oyama (1984) described how the gene has become institutionalised as a quasi-cognitive power, an almost conscious agent. In scientific as well as popular accounts, they “act”, “behave”, “direct”, “control”, “design”, influence, are “responsible for”, are “selfish”, and so on. Oyama sees such superstitious attributions as part of a Western cultural tradition: “Just as traditional thought placed biological forms in the mind of God, so modern thought finds ways of endowing the genes with ultimate formative power”.

  • Indeed, many biologists and psychologists still refer to the genes as “The Book of Life”. I’ve just read on the BBC website that “The genome is the instruction booklet for building a human”. Nearly everyone uses clichĂ©s like “it’s in their DNA”. Little wonder that US President Bill Clinton described the laboratory sequencing of the human genome as “learning the language in which God created life.”

  • People, of course, speak of the role of the “environment” (whatever that is). But the overwhelming image of human development is of the gene-controlled arrangement of gene-produced parts. Psychologists like Steven Pinker (1997) claim that “a linear string of DNA can direct the assembly of an intricate three-dimensional organ that lets us think, feel and learn.”  In The Selfish Gene Richard Dawkins told us “they created us body and mind”. As such they may make humans “clever”; yet also impart nasty human flaws: “arrogant, reckless, lethally predisposed to favour self, tribe and short term futures”, as Edward O. Wilson (2016) puts it in his latest missive on human nature.

  • In this scheme, the workings of the cells are merely servants to the genes’ commands as they build organs like brains, and functions like cognition, according to their own blueprints. Even Nessa Carey (2015), in her book The Epigenetics Revolution (intended to re-write our understanding of genetics, the blurb says), describes DNA as “like a script”, and goes on, “There’s no debate that the DNA blueprint is a starting point”.

  • However, around that pervasive image a whole world order is hinged. These genes come in different “strengths”, forming ranks that, in humans, determine the class structure of societies. A whole intelligence testing movement emerged around that preconception (Richardson & Norgate, 2014). These genes limit the potential of each individual as a pre-determined amount to be more or less “fulfilled”. Parents and teachers view each child as having a lucky or unlucky “deal” of genes. Where children struggle, their biology gets the blame. The view is encouraged by psychologists who just keep paraphrasing a 1938 education commission: “The facts of genetic inequality are something that we cannot escape”, and that, “different children
require types of education varying in certain important respects.”

  • The concept of the gene, in other words, has furnished the scientific roots of a powerful social ideology that finds causes for human nature and social inequality in immutable biology. In doing so it has done much to disarm dissent and protect power and privilege. No wonder that, to this day, it is being so energetically promoted and fiercely defended.

  • Over the years and decades, of course, some scholars have pointed to the superstitious nature of this magical gene. The developmental psychologist Jean Piaget described such attribution of purpose to inert materials as a form of “animism”. It is common among young children who tend to attribute inanimate objects with the qualities of consciousness, free will and intention. Still others have criticised the fundamental flaws in the twin studies that have formed the main instrument of this ideology (Joseph, 2015). And as Oliver James (2016) says, reported correlations between variant DNA sequences and trait values, from genome wide scans, explain very small amounts of trait variance. More critically, none of the correlations have been shown to be causal. But the superstition is now being challenged on new scientific fronts.

  • Take one stark realisation. In the standard view, a living thing is something like a “machine” constructed from the blueprint, the DNA sequence forming the genes. The blueprint uses the apparatus in cells and their physiology to carry out its instructions. This sometimes involves the blueprint making copies of itself to create offspring that do likewise, albeit with occasional mistakes or mutations. And so it has been across evolution from the first blueprint.

  • But where did that first blueprint come from? No-one can say. It’s a classic chicken and egg conundrum. Researchers have shown how RNA molecules may have formed from readily available constituents to store information for protein production (a function subsequently taken over by the more stable DNA). But that still doesn’t explain how they acquired the specification - the code or blueprint – for creating an organism and all its adaptations, as in the standard view. Nor does it explain how all the machinery needed to read and follow the blueprint happened to be there in just the right place at the right time?

  • The unavoidable answer is that the “machine” existed before the genes as a self-assembled entity; the genes (whether directly as DNA, or via RNA) came later. Laboratory experiments have supported the plausibility of this explanation for the origins of life. Self-organised molecular ensembles, including RNA precursors, that “feed”, develop, grow, reproduce, evolve, and so on, have been created in the laboratory without genes as such (see e.g. Shenhav et al., 2005). As Shapiro (2013) explains, such biochemical networks constitute a “toolbox” of cell processes capable of generating a virtually endless set of DNA sequence structures.

  • So if genes only came later, what, then, is their true role? Emphatically not, it seems, as the “original” recipes, designers and controllers of life, at all. More likely as templates for molecular components needed regularly by the already living thing: a kind of facility for “just in time” production of parts needed on a recurring basis.

  • As physiologist Denis Noble (2015) explained, “the modern synthesis has got causality in biology wrong. Genes, after all, if they’re defined as DNA sequences, are purely passive. DNA on its own does absolutely nothing until activated by the rest of the system
DNA is not a cause in an active sense
it is better described as a passive data base which is used by the organism to enable it to make the proteins that it requires.” (See also the summary in Noble et al., 2014).

  • Genes, that is, are servants, not masters, of the development of form and individual differences. Genes do serve as templates for proteins: but not under their own direction. And, as entirely passive strings of chemicals, it is logically impossible for them to initiate and steer development in any sense. Instead, attention has shifted to the “system” – the cells, their physiology, cognition and behavior and (in humans) complex social cognition: a vast, interacting, multi-level locus of control, responding to environmental changes and using genes accordingly.

  • For example, within the cell, processes are self-organised around extensive, interacting, signaling networks sensitive to environmental changes. These networks recruit arrays of transcription and related factors according to the dynamics of current needs and contexts. A structural gene is only transcribed under the direction of such factors acting as a team.

  • Then a whole lot of others things happen. In the development of complex traits, these obfuscate any direct correlation between gene variations and individual differences. For example, it used to be thought that the gene template rigidly determines one - and only one - protein. However, we now know of extensive re-arrangements of the gene products according to the wider system dynamics. In that way, many different proteins, with potentially widely different functions, can be produced from the same gene.

  • By 2003 it was known that at least 74 per cent of human gene products can be alternatively spliced in this way. We now know it is probably many more than that.

  • These “epigenetic” discoveries alone would make it difficult to correlate genetic and trait variations. But there have been many others. For example, genes are inherited by offspring, of course. But environments experienced by mothers before or during pregnancy, such as stress or malnutrition, can modify the way those genes are utilized during the offspring’s development. These modifications can, in turn, affect development throughout life and even on to subsequent generations. These effects appear to be “genetic” although they are “environmental”.

  • The myth of the pontifical gene has been exposed in numerous other ways. Gene sequences, we now know, can be deliberately modified (“mutated”) during development by the demands of changing environments as detected by the system as a whole. For example, it is now known that alternatively spliced RNA – the first product of gene transcription - can be reverse transcribed and inserted into the genome. As Mae-Wan Ho (2014) explained, “numerous mechanisms for generating mutations are involved that appear to be under the control of the cell or organism as a whole in different environmental contexts”. That is, environments directly instruct the organism how to vary, and how such variations are inherited (see also Niles et al., 2014).

  • This is now referred to as natural genetic engineering, or NGE. In a paper in Physics of Life Reviews James Shapiro (2013) says that “the standard model of a ‘Read-Only’ tape that feeds instructions to the rest of the cell about individual characters” is a “dangerous oversimplification.” Now, he says, “we have to reconsider the genome as a ‘read–write’ (RW) information storage system”.

  • On his blog in HuffPost Science (Apr 30, 2013), Shapiro says, “NGE is shorthand to summarize all the biochemical mechanisms cells have to cut, splice, copy, polymerize and otherwise manipulate the structure of internal DNA molecules, transport DNA from one cell to another, or acquire DNA from the environment. Totally novel sequences can result from de novo untemplated polymerization or reverse transcription of processed RNA molecules.”

  • One startling implication is that organisms can help direct their own evolution as well as their development. On the one hand this has raised fundamental debates about “non-Darwinian evolution” and the inheritance of acquired (Lamarckian) characteristics. On the other, it is being increasingly realised that the fundamental organisation and variation of life lies in the whole system, not the genes. This is what is needed in changing environments, and what evolution has provided in self-organising, dynamical systems at various levels.
  • We still have little understanding of such systems and how they guide development, especially in complex functions like cognition. The (mis)direction of attention and resources at deterministic genes hasn’t helped. Even at the level of the single cell, today’s molecular biologists report “intelligence” in bacteria; “cognitive resources” in single cells; “bio-information intelligence”; “cell intelligence”; “metabolic memory”; and “cell knowledge” – all terms appearing in recent literature. And “Do cells think?” is the title of a paper by Sharad Ramanathan and James Broach in the journal Cellular and Molecular Life Sciences. These intelligent functions – using, but not determined by, genes – have been vastly enhanced in the evolution of physiology, brains, cognition, behaviour and human social cognition (for fuller discussion and references see Richardson, 2014).

  • Such discoveries are presenting stark implications for our understanding of genes. In complex, adaptable traits there is no direct mapping from genes through development to individual differences. The genes are crucial, of course, but nearly all genetic variation is irrelevant to trait variation. Most traits crucial for survival are buffered (canalised) against such genetic variations. As with choosing which font you type with, most gene mutations and subsequent protein variations are, except in rare deleterious forms, irrelevant to function. Such is the exquisite adaptability of the evolved systems.

  • For example, most genetic mutations can be dealt with in development in the way you can vary your journey from A to B.  Alternative pathways are created to reach the desired endpoint. In study of a number of biochemical pathways reported in the journal BioSystems, Andreas Wagner and Jeremiah Wright (2007) concluded that “multiple alternative pathways
are the rule rather than the exception
such pathways can continue to function despite [genetic] changes that may impair one intermediate regulator. Our results underscore the importance of systems biology approaches to understand functional and evolutionary constraints on genes and proteins.”

  • Likewise, Frederik Nijhout and colleagues (2015) were surprised to discover that, in humans, many of the genes for critical enzymes exhibit large degrees of variation. However, at the level of the trait (metabolic systems critical for human health) there was little variation of function. That is, the genetic variations scarcely matter. Only in rare cases will the system fail to cope, so that disease ensues.

  • So it is with some astonishment that experiments have revealed that large portions of the genome can be deleted without noticeable effects on basic functions. The common yeast Saccharomyces cerevisiae has 6000 genes. Experiments have shown that up to 80 per cent of them can be deleted without detriment to normal function under optimum conditions (Razinkov, I.V. et al., 2015). This observation attests to the robustness of biological networks even in single cells.

  • This multi-level regulation of gene utilisation is being increasingly appreciated in psychology and behavioral sciences. As Mae-Wan Ho (2014) notes, “researchers are identifying hundreds and thousands of genes that are affected by our subjective mental states, and that “the emerging field of human social genomics is demonstrating that social conditions, especially our subjective perceptions thereof can radically change our gene expression states”. No doubt feelings arising from an inferior place in a social class system will have similar effects (Odgers, 2015), especially if the victim has been led to believe that it’s due to inferior genes.
  • Not surprisingly, then, a major re-definition of the gene is now under way. As Shapiro (2013) notes, we have, up until now, been using “a theoretical construct whose functional properties and physical structure have never been possible to define rigorously”. In many quarters the very term is being replaced by more semantically neutral concepts like “coding sequence” (or CDS), or “DNA elements”. The close identification of genes with “genesis” is dying.

  • Why has this research, challenging a superstitious model of a pontifical gene, been evaded for so long, especially in psychology? Perhaps it is not so surprising. As Thomas Kuhn (1957) wrote about the first Copernican revolution, “If Copernicus’ proposal had had no consequences outside astronomy, it would have been neither so long delayed nor so strenuously resisted.”

  • This second one threatens even deeper, albeit, for most humans, positive and liberating, consequences. Imagine that the social class structure is not, in fact, a genetic caste system; that human potential is not written in genes as pre-determined limits; that our cognitive abilities are not fixed as relics of the stone-age (as psychologists like Steven Pinker insist); that the marvellous mental variation among humans is created from multi-level developmental systems; and that, as in human history, quite different futures are possible. No wonder so many are finding it hard to swallow.

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